Can insulin-like growth factor 1 (IGF-1), IGF-1 receptor connective tissue growth factor and Ki-67 labelling index have a prognostic role in pulmonary carcinoids?

PubMed

Kanakis, Georgios A; Grimelius, Lars; Papaioannou, Dimitrios; Kaltsas, Gregory; Tsolakis, Apostolos V

2018-04-27

Altered expression of Insulin-like Growth Factor-1 (IGF-1), its receptor (IGF-1R), Connective Tissue Growth Factor (CTGF) and Hypoxia Inducible Factor-1 (HIF-1), has been implicated in tumorigenesis. So far, these factors have not been studied systematically in Pulmonary Carcinoids (PCs). To examine IGF-1, IGF-1R, CTGF and HIF-1 expression in PCs, and assess their prognostic value over established factors. Retrospective study of 121 PCs (104 Typical and 17 Atypical). The expression of growth factors was studied immunohistochemically and tumors were considered positive if immunoreactivity appeared in >50% of cells. All studied parameters were expressed in the majority of tumors (IGF-1, IGF-1R, CTGF and HIF-1, in 78.5%, 67%, 72% and 78%, respectively). Their expression tended to be more frequent in TCs and in tumors with Ki-67≤2% (significant only for HIF-1; 82 vs. 53%; p=0.023 and 83 vs. 63%; p=0.025 respectively). CTGF was the only factor correlated with more extensive disease (larger size; presence of lymph node and distant metastases). According to logistic regression analysis, only advanced age, Ki-67≥3.4% and lymph node involvement could predict the development of distant metastases. IGF-1, IGF-1R, CTGF and HIF-1 are avidly expressed in PCs; however, their presence did not appear to be of statistically significant value over established prognostic factors.

Intravoxel Incoherent Motion and Quantitative Non-Gaussian Diffusion MR Imaging: Evaluation of the Diagnostic and Prognostic Value of Several Markers of Malignant and Benign Breast Lesions.

PubMed

Iima, Mami; Kataoka, Masako; Kanao, Shotaro; Onishi, Natsuko; Kawai, Makiko; Ohashi, Akane; Sakaguchi, Rena; Toi, Masakazu; Togashi, Kaori

2018-05-01

Purpose To investigate the performance of integrated approaches that combined intravoxel incoherent motion (IVIM) and non-Gaussian diffusion parameters compared with the Breast Imaging and Reporting Data System (BI-RADS) to establish multiparameter thresholds scores or probabilities by using Bayesian analysis to distinguish malignant from benign breast lesions and their correlation with molecular prognostic factors. Materials and Methods Between May 2013 and March 2015, 411 patients were prospectively enrolled and 199 patients (allocated to training [n = 99] and validation [n = 100] sets) were included in this study. IVIM parameters (flowing blood volume fraction [fIVIM] and pseudodiffusion coefficient [D*]) and non-Gaussian diffusion parameters (theoretical apparent diffusion coefficient [ADC] at b value of 0 sec/mm 2 [ADC 0 ] and kurtosis [K]) by using IVIM and kurtosis models were estimated from diffusion-weighted image series (16 b values up to 2500 sec/mm 2 ), as well as a synthetic ADC (sADC) calculated by using b values of 200 and 1500 (sADC 200-1500 ) and a standard ADC calculated by using b values of 0 and 800 sec/mm 2 (ADC 0-800 ). The performance of two diagnostic approaches (combined parameter thresholds and Bayesian analysis) combining IVIM and diffusion parameters was evaluated and compared with BI-RADS performance. The Mann-Whitney U test and a nonparametric multiple comparison test were used to compare their performance to determine benignity or malignancy and as molecular prognostic biomarkers and subtypes of breast cancer. Results Significant differences were found between malignant and benign breast lesions for IVIM and non-Gaussian diffusion parameters (ADC 0 , K, fIVIM, fIVIM · D*, sADC 200-1500, and ADC 0-800 ; P < .05). Sensitivity and specificity for the validation set by radiologists A and B were as follows: sensitivity, 94.7% and 89.5%, and specificity, 75.0% and 79.2% for sADC 200-1500 , respectively; sensitivity, 94.7% and 96.1%, and specificity, 75.0% and 66.7%, for the combined thresholds approach, respectively; sensitivity, 92.1% and 92.1%, and specificity, 83.3% and 66.7%, for Bayesian analysis, respectively; and sensitivity and specificity, 100% and 79.2%, for BI-RADS, respectively. The significant difference in values of sADC 200-1500 in progesterone receptor status (P = .002) was noted. sADC 200-1500 was significantly different between histologic subtypes (P = .006). Conclusion Approaches that combined various IVIM and non-Gaussian diffusion MR imaging parameters may provide BI-RADS-equivalent scores almost comparable to BI-RADS categories without the use of contrast agents. Non-Gaussian diffusion parameters also differed by biologic prognostic factors. © RSNA, 2017 Online supplemental material is available for this article.

Independent Prognostic Value of Stroke Volume Index in Patients With Immunoglobulin Light Chain Amyloidosis.

PubMed

2018-05-01

Heart involvement is the most important prognostic determinant in AL amyloidosis patients. Echocardiography is a cornerstone for the diagnosis and provides important prognostic information. We studied 754 patients with AL amyloidosis who underwent echocardiographic assessment at the Mayo Clinic, including a Doppler-derived measurement of stroke volume (SV) within 30 days of their diagnosis to explore the prognostic role of echocardiographic variables in the context of a well-established soluble cardiac biomarker staging system. Reproducibility of SV, myocardial contraction fraction, and left ventricular strain was assessed in a separate, yet comparable, study cohort of 150 patients from the Pavia Amyloidosis Center. The echocardiographic measures most predictive for overall survival were SV index <33 mL/min, myocardial contraction fraction <34%, and cardiac index <2.4 L/min/m 2 with respective hazard ratios (95% confidence intervals) of 2.95 (2.37-3.66), 2.36 (1.96-2.85), and 2.32 (1.91-2.80). For the subset that had left ventricular strain performed, the prognostic cut point was -14% (hazard ratios, 2.70; 95% confidence intervals, 1.84-3.96). Each parameter was independent of systolic blood pressure, Mayo staging system (NT-proBNP [N-terminal pro-B-type natriuretic peptide] and troponin), and ejection fraction on multivariable analysis. Simple predictive models for survival, including biomarker staging along with SV index or left ventricular strain, were generated. SV index prognostic performance was similar to left ventricular strain in predicting survival in AL amyloidosis, independently of biomarker staging. Because SV index is routinely calculated and widely available, it could serve as the preferred echocardiographic measure to predict outcomes in AL amyloidosis patients. © 2018 American Heart Association, Inc.

Amino acid tracers in PET imaging of diffuse low-grade gliomas: a systematic review of preoperative applications.

PubMed

Näslund, Olivia; Smits, Anja; Förander, Petter; Laesser, Mats; Bartek, Jiri; Gempt, Jens; Liljegren, Ann; Daxberg, Eva-Lotte; Jakola, Asgeir Store

2018-05-24

Positron emission tomography (PET) imaging using amino acid tracers has in recent years become widely used in the diagnosis and prediction of disease course in diffuse low-grade gliomas (LGG). However, implications of preoperative PET for treatment and prognosis in this patient group have not been systematically studied. The aim of this systematic review was to evaluate the preoperative diagnostic and prognostic value of amino acid PET in suspected diffuse LGG. Medline, Cochrane Library, and Embase databases were systematically searched using keywords "PET," "low-grade glioma," and "amino acids tracers" with their respective synonyms. Out of 2137 eligible studies, 28 met the inclusion criteria. Increased amino acid uptake (lesion/brain) was consistently reported among included studies; in 25-92% of subsequently histopathology-verified LGG, in 83-100% of histopathology-verified HGG, and also in some non-neoplastic lesions. No consistent results were found in studies reporting hot spot areas on PET in MRI-suspected LGG. Thus, the diagnostic value of amino acid PET imaging in suspected LGG has proven difficult to interpret, showing clear overlap and inconsistencies among reported results. Similarly, the results regarding the prognostic value of PET in suspected LGG and the correlation between uptake ratios and the molecular tumor status of LGG were conflicting. This systematic review illustrates the difficulties with prognostic studies presenting data on group-level without adjustment for established clinical prognostic factors, leading to a loss of additional prognostic information. We conclude that the prognostic value of PET is limited to analysis of histological subgroups of LGG and is probably strongest when using kinetic analysis of dynamic FET uptake parameters.

Clinical Significance of Soluble Intercellular Adhesion Molecule-1 and Interleukin-6 in Patients with Extrahepatic Cholangiocarcinoma.

PubMed

Shimura, Tatsuo; Shibata, Masahiko; Gonda, Kenji; Kofunato, Yasuhide; Okada, Ryo; Ishigame, Teruhide; Kimura, Takashi; Kenjo, Akira; Marubashi, Shigeru; Kono, Koji; Takenoshita, Seiichi

2017-09-19

Purpose/Aim: Although several prognostic factors for extrahepatic cholangiocarcinoma (EHC) have been reported, preoperative prognostic factors have yet to be established. We investigated the serum concentration of angiogenic, inflammatory, and nutritional parameters. Twenty-five patients with EHC were enrolled before starting treatment. Preoperative prognostic factors were identified using multivariate analyses. The serum soluble intercellular adhesion molecule-1 (sICAM-1) levels were significantly higher in the patients with EHC (436.0 ± 43.2 ng/ml) than in the healthy volunteers (228.6 ± 22.0 ng/ml) (p <.001). In addition, the serum IL-6 levels were significantly higher in the patients (18.0 ± 5.6 pg/ml) than in the healthy volunteers (5.7 ± 0.8 pg/ml) (p <.05). The serum IL-6 and sICAM-1 showed a strong correlation (r = 0.559) in the patients with EHC (p <.01). The serum IL-6 (area under the curve = 0.764, p =.030, cut-off level = 11.6) and sICAM-1 (area under the curve = 0.818, p =.007, cutoff level = 322.6) were revealed to be useful as prognostic factors by the receiver operating characteristic curves. The high IL-6 group and the high sICAM-1 group showed poorer DSS than those of the respective low groups. In the multivariate analysis, IL-6 (hazard ratio: 1.050, 95% confidence interval: 1.002-1.100, p =.043) and sICAM-1 (hazard ratio: 1.009, 95% confidence interval: 1.002-1.015, p =.009) were independent prognostic factors for DSS. IL-6 and sICAM-1 were independent preoperative prognostic factors in EHC patients, causing continuous inflammation and malnutrition in collaboration with other pro-angiogenic factors.

[MRI-Based Ratio of Fetal Lung to Body Volume as New Prognostic Marker for Chronic Lung Disease in Patients with Congenital Diaphragmatic Hernia].

PubMed

Winkler, Melissa M; Weis, Meike; Henzler, Claudia; Weiß, Christel; Kehl, Sven; Schoenberg, Stefan O; Neff, Wolfgang; Schaible, Thomas

2017-03-01

Background Our aim was to evaluate the prognostic value of magnetic resonance imaging (MRI)-based ratio of fetal lung volume (FLV) to fetal body volume (FBV) as a marker for development of chronic lung disease (CLD) in fetuses with congenital diaphragmatic hernia (CDH). Patients and Methods FLV and FBV were measured and the individual FLV/FBV ratio was calculated in 132 fetuses. Diagnosis of CLD was established following prespecified criteria and graded into mild/moderate/severe if present. Logistic regression analysis was used to calculate the probability of postnatal development of CLD in dependence of the FLV/FBV ratio. Receiver operating characteristic curves were analysed by calculating the area under the curve to evaluate the prognostic accuracy of this marker. Results 61 of 132 fetuses developed CLD (46.21%). The FLV/FBV ratio was significantly lower in fetuses with CLD (p=0.0008; AUC 0.743). Development of CLD was significantly associated with thoracic herniation of liver parenchyma (p<0.0001), requirement of extracorporal membrane oxygenation (ECMO) (p<0.0001) and gestational age at delivery (p=0.0052). Conclusion The MRI-based ratio of FLV to FBV is a highly valuable prenatal parameter for development of CLD. The ratio is helpful for early therapeutic decisions by estimating the probability to develop CLD. Perinatally, gestational age at delivery and ECMO requirement are useful additional parameters to further improve prediction of CLD. © Georg Thieme Verlag KG Stuttgart · New York.

Meta-analysis of prognostic value of inflammation parameter in breast cancer.

PubMed

Chen, Jie; Pan, Yuqin; He, Bangshun; Ying, Houqun; Sun, Huiling; Deng, Qiwen; Liu, Xian; Wang, Shukui

2018-01-01

Recently, increasing studies investigated the association between inflammation parameter such as neutrophil to lymphocyte ratio (NLR) and the prognosis of cancers. However, the clinical and prognostic significance of NLR in breast cancer remains controversial. This meta-analysis was conducted to establish the overall accuracy of the NLR test in the diagnosis of breast cancer. A comprehensive search of the literature was conducted using PubMed and Web of Science. Six studies dating up to July 2014 with 2267 patients were enrolled in the present study. STATA 11.0 software (STATA Corporation, College Station, TX, USA) was selected for data analysis. In order to evaluate the association between NLR and overall survival (OS), disease-free survival (DFS), recurrence-free survival or cancer-specific survival, the hazard ratios (HRs), and their 95% confidence intervals (CIs) were extracted. Subgroup analyses showed that NLR was a strong prognostic factor for OS in multivariate analysis (HR = 2.81, 95% CI = 2.13-3.71, P H = 0.992) and without metastasis (HR = 1.45, 95% CI = 0.37-5.66, P H < 0.001). Elevated NLR was associated with a high risk for DFS in subgroups of multivariate analysis (HR = 2.16, 95% CI = 1.67-2.80, P H = 0.977) and mixed metastasis (HR = 2.13, 95% CI = 1.38-3.30, P H = 0.84). In summary, NLR may be considered as a predictive factor for patients with breast cancer.

Establishment and Validation of GV-SAPS II Scoring System for Non-Diabetic Critically Ill Patients.

PubMed

Liu, Wen-Yue; Lin, Shi-Gang; Zhu, Gui-Qi; Poucke, Sven Van; Braddock, Martin; Zhang, Zhongheng; Mao, Zhi; Shen, Fei-Xia; Zheng, Ming-Hua

2016-01-01

Recently, glucose variability (GV) has been reported as an independent risk factor for mortality in non-diabetic critically ill patients. However, GV is not incorporated in any severity scoring system for critically ill patients currently. The aim of this study was to establish and validate a modified Simplified Acute Physiology Score II scoring system (SAPS II), integrated with GV parameters and named GV-SAPS II, specifically for non-diabetic critically ill patients to predict short-term and long-term mortality. Training and validation cohorts were exacted from the Multiparameter Intelligent Monitoring in Intensive Care database III version 1.3 (MIMIC-III v1.3). The GV-SAPS II score was constructed by Cox proportional hazard regression analysis and compared with the original SAPS II, Sepsis-related Organ Failure Assessment Score (SOFA) and Elixhauser scoring systems using area under the curve of the receiver operator characteristic (auROC) curve. 4,895 and 5,048 eligible individuals were included in the training and validation cohorts, respectively. The GV-SAPS II score was established with four independent risk factors, including hyperglycemia, hypoglycemia, standard deviation of blood glucose levels (GluSD), and SAPS II score. In the validation cohort, the auROC values of the new scoring system were 0.824 (95% CI: 0.813-0.834, P< 0.001) and 0.738 (95% CI: 0.725-0.750, P< 0.001), respectively for 30 days and 9 months, which were significantly higher than other models used in our study (all P < 0.001). Moreover, Kaplan-Meier plots demonstrated significantly worse outcomes in higher GV-SAPS II score groups both for 30-day and 9-month mortality endpoints (all P< 0.001). We established and validated a modified prognostic scoring system that integrated glucose variability for non-diabetic critically ill patients, named GV-SAPS II. It demonstrated a superior prognostic capability and may be an optimal scoring system for prognostic evaluation in this patient group.

A Prognostic Gene Expression Profile That Predicts Circulating Tumor Cell Presence in Breast Cancer Patients

PubMed Central

Molloy, Timothy J.; Roepman, Paul; Naume, Bjørn; van't Veer, Laura J.

2012-01-01

The detection of circulating tumor cells (CTCs) in the peripheral blood and microarray gene expression profiling of the primary tumor are two promising new technologies able to provide valuable prognostic data for patients with breast cancer. Meta-analyses of several established prognostic breast cancer gene expression profiles in large patient cohorts have demonstrated that despite sharing few genes, their delineation of patients into “good prognosis” or “poor prognosis” are frequently very highly correlated, and combining prognostic profiles does not increase prognostic power. In the current study, we aimed to develop a novel profile which provided independent prognostic data by building a signature predictive of CTC status rather than outcome. Microarray gene expression data from an initial training cohort of 72 breast cancer patients for which CTC status had been determined in a previous study using a multimarker QPCR-based assay was used to develop a CTC-predictive profile. The generated profile was validated in two independent datasets of 49 and 123 patients and confirmed to be both predictive of CTC status, and independently prognostic. Importantly, the “CTC profile” also provided prognostic information independent of the well-established and powerful ‘70-gene’ prognostic breast cancer signature. This profile therefore has the potential to not only add prognostic information to currently-available microarray tests but in some circumstances even replace blood-based prognostic CTC tests at time of diagnosis for those patients already undergoing testing by multigene assays. PMID:22384245

Prognostic value of 18F-choline PET/CT metabolic parameters in patients with metastatic castration-resistant prostate cancer treated with abiraterone or enzalutamide.

PubMed

Caroli, Paola; De Giorgi, Ugo; Scarpi, Emanuela; Fantini, Lorenzo; Moretti, Andrea; Galassi, Riccardo; Celli, Monica; Conteduca, Vincenza; Rossi, Lorena; Bianchi, Emanuela; Paganelli, Giovanni; Matteucci, Federica

2018-03-01

The role of 18F-choline positron emission tomography/computed tomography (FCH-PET/CT) in patients with metastatic castration-resistant prostate cancer (mCRPC) has been firmly established in recent years. We analyzed the prognostic value of functional parameters such as mean standardized uptake volume (SUVmean), maximum standardized uptake volume (SUVmax), metabolic total volume (MTV; the volume of interest consisting of all spatially connected voxels within a fixed threshold of 40% of the SUVmax), and total lesion activity (TLA: the product of MTV and mean standardized uptake value) estimated with FCH-PET/CT in mCRPC patients in progression after docetaxel and treated with new antiandrogen receptor therapies, abiraterone or enzalutamide. We retrospectively studied 94 mCRPC patients, mean age 74 years (range 42-90), previously treated with docetaxel who were treated with either abiraterone (n = 52) or enzalutamide (n = 42). An FCH-PET/CT was performed at baseline, and patients were evaluated on a monthly basis for serological PSA response and every 3 months for radiological response. We measured MTV, SUVmean, SUVmax and TLA for each lesion and analyzed the sum of MTV (SMTV), SUVmean (SSUVmean), SUVmax (SSUVmax) and TLA (STLA) values for a maximum of 20 lesions. Univariate analysis was used to correlate these data with PFS and OS. We observed a median SMTV of 130 cm 3 , median SSUVmax of 106.5 and a median STLA of 495,070. All of these parameters were significant for PFS and OS in univariate analysis, while only STLA was significant for PFS and OS in multivariate analysis after adjusting for lesion and age (p < 0.0001 and p = 0.001, respectively). Baseline PSA values maintained a certain reliability for OS (p = 0.034). Semiquantitative parameters of FCH-PET/CT play a prognostic role in mCRCP patients treated with abiraterone or enzalutamide.

Health-related quality-of-life parameters as independent prognostic factors in advanced or metastatic bladder cancer.

PubMed

Roychowdhury, D F; Hayden, A; Liepa, A M

2003-02-15

This retrospective analysis examined prognostic significance of health-related quality-of-life (HRQoL) parameters combined with baseline clinical factors on outcomes (overall survival, time to progressive disease, and time to treatment failure) in bladder cancer. Outcome and HRQoL (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30) data were collected prospectively in a phase III study assessing gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in locally advanced or metastatic bladder cancer. Prespecified baseline clinical factors (performance status, tumor-node-metastasis staging, visceral metastases [VM], alkaline phosphatase [AP] level, number of metastatic sites, prior radiotherapy, disease measurability, sex, time from diagnosis, and sites of disease) and selected HRQoL parameters (global QoL; all functional scales; symptoms: pain, fatigue, insomnia, dyspnea, anorexia) were evaluated using Cox's proportional hazards model. Factors with individual prognostic value (P <.05) on outcomes in univariate models were assessed for joint prognostic value in a multivariate model. A final model was developed using a backward selection strategy. Patients with baseline HRQoL were included (364 of 405, 90%). The final model predicted longer survival with low/normal AP levels, no VM, high physical functioning, low role functioning, and no anorexia. Positive prognostic factors for time to progressive disease were good performance status, low/normal AP levels, no VM, and minimal fatigue; for time to treatment failure, they were low/normal AP levels, minimal fatigue, and no anorexia. Global QoL was a significant predictor of outcome in univariate analyses but was not retained in the multivariate model. HRQoL parameters are independent prognostic factors for outcome in advanced bladder cancer; their prognostic importance needs further evaluation.

Comparative prognostic relevance of breast intra-tumoral microvessel density evaluated by CD105 and CD146: A pilot study of 42 cases.

PubMed

Martinez, Leandro Marcelo; Labovsky, Vivian; Calcagno, María de Luján; Davies, Kevin Mauro; Rivello, Hernán Garcia; Wernicke, Alejandra; Calvo, Juan Carlos; Chasseing, Norma Alejandra

2016-04-01

Angiogenesis is a key process for metastatic progression. While it has been established that the evaluation of breast tumoral microvessel density by CD105 marker is a potential prognostic parameter, its evaluation by CD146 marker has been poorly studied. The purpose of this study was to compare the prognostic value of intra-tumoral microvessel density assayed by CD105 and CD146 in early breast cancer patients. 42 women with breast infiltrative ductal carcinoma (I and II-stages) were retrospectively reviewed. Intra-tumoral microvessel density was immunohistochemically examined using antibodies anti-CD105 and CD146 in paraffin-embedded tissues, and their association with classical prognostic-markers, metastatic recurrence, metastasis-free survival and overall survival was analyzed. High microvessel density assessed by CD146 was significantly associated with a higher risk of developing metastasis (p=0.0310) and a shorter metastasis-free survival (p=0.0197). In contrast, when we used the CD105-antibody, we did not find any significant association. Finally, CD146 showed to be an independent predictive indicator for metastasis-free survival (p=0.0055). Our data suggest that the intra-tumoral microvessel density evaluated by CD146 may be a more suitable predictor of metastatic development than that evaluated by CD105 in early breast cancer. Copyright © 2016 Elsevier GmbH. All rights reserved.

The prognostic impact of clinical and CT parameters in patients with pontine hemorrhage.

PubMed

Dziewas, Rainer; Kremer, Marion; Lüdemann, Peter; Nabavi, Darius G; Dräger, Bianca; Ringelstein, Bernd

2003-01-01

In patients with pontine hemorrhage (PH), an accurate prognostic assessment is critical for establishing a reasonable therapeutic approach. The initial clinical symptoms and computed tomography (CT) features were analyzed with multivariate regression analysis in 39 consecutive patients with PH. PHs were classified into three types: (1) large paramedian, (2) basal or basotegmental and (3) lateral tegmental, and the hematomas' diameters were measured. The patients' outcome was evaluated. Twenty-seven patients (69%) died and 12 (31%) survived for more than 1 year after PH. The symptom most predictive of death was coma on admission. The large paramedian type of PH predicted a poor prognosis, whereas the lateral tegmental type was associated with a favorable outcome. The transverse hematoma diameter was also related to outcome, with the threshold value found to be 20 mm. We conclude that PH outcome can be estimated best by combining the CT parameters 'large paramedian PH' and 'transverse diameter >/=20 mm' with the clinical variable 'coma on admission'. Survival is unlikely if all 3 features are present, whereas survival may be expected if only 1 or none of these features is found. Copyright 2003 S. Karger AG, Basel

Early Prognostication Markers in Cardiac Arrest Patients Treated with Hypothermia

PubMed Central

Karapetkova, Maria; Koenig, Matthew A.; Jia, Xiaofeng

2015-01-01

Background and purpose Established prognostication markers, such as clinical findings, electroencephalography (EEG), and biochemical markers, used by clinicians to predict neurologic outcome after cardiac arrest (CA) are altered under therapeutic hypothermia (TH) conditions and their validity remains uncertain. Methods MEDLINE and EMBASE were searched for evidence on the current standards for neurologic outcome prediction for out-of-hospital CA patients treated with TH and the validity of a wide range of prognostication markers. Relevant studies that suggested one or several established biomarkers, and multimodal approaches for prognostication were included and reviewed. Results While the prognostic accuracy of various tests has been questioned after TH, pupillary light reflexes and somatosensory evoked potentials (SSEP) are still strongly associated with negative outcome for early prognostication. Increasingly, EEG background activity has also been identified as a valid predictor for outcome after 72 hours after CA and a preferred prognostic method in clinical settings. Neuroimaging techniques, such as MRI and CT, can identify functional and structural brain injury, but are not readily available at the patient’s bedside because of limited availability and high costs. Conclusions A multimodal algorithm composed of neurological examination, EEG-based quantitative testing, and SSEP, in conjunction with newer MRI sequences, if available, holds promise for accurate prognostication in CA patients treated with TH. In order to avoid premature withdrawal of care, prognostication should be performed later than 72 hours after CA. PMID:26228521

Early prognostication markers in cardiac arrest patients treated with hypothermia.

PubMed

Karapetkova, M; Koenig, M A; Jia, X

2016-03-01

Established prognostication markers, such as clinical findings, electroencephalography (EEG) and biochemical markers, used by clinicians to predict neurological outcome after cardiac arrest (CA) are altered under therapeutic hypothermia (TH) conditions and their validity remains uncertain. MEDLINE and Embase were searched for evidence on the current standards for neurological outcome prediction for out-of-hospital CA patients treated with TH and the validity of a wide range of prognostication markers. Relevant studies that suggested one or several established biomarkers and multimodal approaches for prognostication are included and reviewed. Whilst the prognostic accuracy of various tests after TH has been questioned, pupillary light reflexes and somatosensory evoked potentials are still strongly associated with negative outcome for early prognostication. Increasingly, EEG background activity has also been identified as a valid predictor for outcome after 72 h after CA and a preferred prognostic method in clinical settings. Neuroimaging techniques, such as magnetic resonance imaging and computed tomography, can identify functional and structural brain injury but are not readily available at the patient's bedside because of limited availability and high costs. A multimodal algorithm composed of neurological examination, EEG-based quantitative testing and somatosensory evoked potentials, in conjunction with newer magnetic resonance imaging sequences, if available, holds promise for accurate prognostication in CA patients treated with TH. In order to avoid premature withdrawal of care, prognostication should be performed more than 72 h after CA. © 2015 EAN.

A nomogram to predict prognostic values of various inflammatory biomarkers in patients with esophageal squamous cell carcinoma

PubMed Central

Liu, Jin-Shi; Huang, Ying; Yang, Xun; Feng, Ji-Feng

2015-01-01

Background: Inflammation plays an important role in cancer progression and prognosis. However, the prognostic values of inflammatory biomarkers in esophageal cancer (EC) were not established. In the present study, therefore, we initially used a nomogram to predict prognostic values of various inflammatory biomarkers in patients with esophageal squamous cell carcinoma (ESCC). Methods: A total of 326 ESCC patients were included in this retrospective study. Glasgow prognostic score (GPS), neutrophil lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR) and lymphocyte monocyte ratio (LMR) were analyzed in the current study. Kaplan-Meier method was used to calculate the cancer-specific survival (CSS). Cox regression analysis was also performed to evaluate the prognostic factors. A nomogram was established to predict the prognosis for CSS. Results: Patients were divided into 3 groups according to GPS (GPS 0, 1 and 2) and 2 groups according to NLR (≤3.45 and >3.45), PLR (≤166.5 and >166.5) and LMR (≤2.30 and >2.30). The 5-year CSS in patients with GPS 0, 1 and 2 were 49.2%, 26.8% and 11.9%, respectively (P<0.001). In addition, patients with NLR (>3.45), PLR (>166.5) and LMR (≤2.30) were significantly associated with decreased CSS, respectively (P<0.001). Multivariate analysis revealed that GPS (P<0.001), PLR (P=0.002) and LMR (P=0.002) were independent prognostic factors in patients with ESCC. In addition, a nomogram was established according to all significantly independent factors for CSS. The Harrell’s c-index for CSS prediction was 0.72. Conclusion: GPS, PLR and LMR were potential prognostic biomarkers in patients with ESCC. The nomogram based on CSS could be used as an accurately prognostic prediction for patients with ESCC. PMID:26328248

LPL is the strongest prognostic factor in a comparative analysis of RNA-based markers in early chronic lymphocytic leukemia.

PubMed

Kaderi, Mohd Arifin; Kanduri, Meena; Buhl, Anne Mette; Sevov, Marie; Cahill, Nicola; Gunnarsson, Rebeqa; Jansson, Mattias; Smedby, Karin Ekström; Hjalgrim, Henrik; Jurlander, Jesper; Juliusson, Gunnar; Mansouri, Larry; Rosenquist, Richard

2011-08-01

The expression levels of LPL, ZAP70, TCL1A, CLLU1 and MCL1 have recently been proposed as prognostic factors in chronic lymphocytic leukemia. However, few studies have systematically compared these different RNA-based markers. Using real-time quantitative PCR, we measured the mRNA expression levels of these genes in unsorted samples from 252 newly diagnosed chronic lymphocytic leukemia patients and correlated our data with established prognostic markers (for example Binet stage, CD38, IGHV gene mutational status and genomic aberrations) and clinical outcome. High expression levels of all RNA-based markers, except MCL1, predicted shorter overall survival and time to treatment, with LPL being the most significant. In multivariate analysis including the RNA-based markers, LPL expression was the only independent prognostic marker for overall survival and time to treatment. When studying LPL expression and the established markers, LPL expression retained its independent prognostic strength for overall survival. All of the RNA-based markers, albeit with varying ability, added prognostic information to established markers, with LPL expression giving the most significant results. Notably, high LPL expression predicted a worse outcome in good-prognosis subgroups, such as patients with mutated IGHV genes, Binet stage A, CD38 negativity or favorable cytogenetics. In particular, the combination of LPL expression and CD38 could further stratify Binet stage A patients. LPL expression is the strongest RNA-based prognostic marker in chronic lymphocytic leukemia that could potentially be applied to predict outcome in the clinical setting, particularly in the large group of patients with favorable prognosis.

Independent Prognostic Value of Serum Markers in Diffuse Large B-Cell Lymphoma in the Era of the NCCN-IPI.

PubMed

Melchardt, Thomas; Troppan, Katharina; Weiss, Lukas; Hufnagl, Clemens; Neureiter, Daniel; Tränkenschuh, Wolfgang; Schlick, Konstantin; Huemer, Florian; Deutsch, Alexander; Neumeister, Peter; Greil, Richard; Pichler, Martin; Egle, Alexander

2015-12-01

Several serum parameters have been evaluated for adding prognostic value to clinical scoring systems in diffuse large B-cell lymphoma (DLBCL), but none of the reports used multivariate testing of more than one parameter at a time. The goal of this study was to validate widely available serum parameters for their independent prognostic impact in the era of the National Comprehensive Cancer Network-International Prognostic Index (NCCN-IPI) score to determine which were the most useful. This retrospective bicenter analysis includes 515 unselected patients with DLBCL who were treated with rituximab and anthracycline-based chemoimmunotherapy between 2004 and January 2014. Anemia, high C-reactive protein, and high bilirubin levels had an independent prognostic value for survival in multivariate analyses in addition to the NCCN-IPI, whereas neutrophil-to-lymphocyte ratio, high gamma-glutamyl transferase levels, and platelets-to-lymphocyte ratio did not. In our cohort, we describe the most promising markers to improve the NCCN-IPI. Anemia and high C-reactive protein levels retain their power in multivariate testing even in the era of the NCCN-IPI. The negative role of high bilirubin levels may be associated as a marker of liver function. Further studies are warranted to incorporate these markers into prognostic models and define their role opposite novel molecular markers. Copyright © 2015 by the National Comprehensive Cancer Network.

Prognostic value of (18)F-FDG PET/CT volumetric parameters in recurrent epithelial ovarian cancer.

PubMed

Mayoral, M; Fernandez-Martinez, A; Vidal, L; Fuster, D; Aya, F; Pavia, J; Pons, F; Lomeña, F; Paredes, P

2016-01-01

Metabolic tumour volume (MTV) and total lesion glycolysis (TLG) from (18)F-FDG PET/CT are emerging prognostic biomarkers in various solid neoplasms. These volumetric parameters and the SUVmax have shown to be useful criteria for disease prognostication in preoperative and post-treatment epithelial ovarian cancer (EOC) patients. The purpose of this study was to evaluate the utility of (18)F-FDG PET/CT measurements to predict survival in patients with recurrent EOC. Twenty-six patients with EOC who underwent a total of 31 (18)F-FDG PET/CT studies for suspected recurrence were retrospectively included. SUVmax and volumetric parameters whole-body MTV (wbMTV) and whole-body TLG (wbTLG) with a threshold of 40% and 50% of the SUVmax were obtained. Correlation between PET parameters and progression-free survival (PFS) and the survival analysis of prognostic factors were calculated. Serous cancer was the most common histological subtype (76.9%). The median PFS was 12.5 months (range 10.7-20.6 months). Volumetric parameters showed moderate inverse correlation with PFS but there was no significant correlation in the case of SUVmax. The correlation was stronger for first recurrences. By Kaplan-Meier analysis and log-rank test, wbMTV 40%, wbMTV 50% and wbTLG 50% correlated with PFS. However, SUVmax and wbTLG 40% were not statistically significant predictors for PFS. Volumetric parameters wbMTV and wbTLG 50% measured by (18)F-FDG PET/CT appear to be useful prognostic predictors of outcome and may provide valuable information to individualize treatment strategies in patients with recurrent EOC. Copyright © 2015 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

Immunohistochemical and prognostic analysis of apoptosis and proliferation in uveal melanoma.

PubMed Central

Mooy, C. M.; Luyten, G. P.; de Jong, P. T.; Luider, T. M.; Stijnen, T.; van de Ham, F.; van Vroonhoven, C. C.; Bosman, F. T.

1995-01-01

Neoplasia can be defined as deregulated tissue homeostasis caused by an imbalance between proliferation and apoptosis. Many genes are involved in the maintenance of tissue homeostasis, eg, the c-myc oncoprotein, which is an important regulator of cell proliferation and Bcl-2 protein, which is involved in the regulation of apoptosis. We studied retrospectively indices of proliferation, such as mitotic count and the Mib-1 index, on 51 uveal melanomas and compared their prognostic significance with established indicators of prognosis such as cell type and tumor size. Along the same line we investigated the expression of the regulating proteins c-myc and Bcl-2. Of all parameters tested, the largest tumor diameter and mitotic count were most strongly associated with tumor-related death (P < 0.001 and P = 0.005, respectively). In addition, cell type, the presence of epithelioid cells, the Mib-1 index, and the percentage of cytoplasmic c-myc-positive cells were significant predictive factors. Multivariate analysis showed that the Mib-1 index, largest tumor diameter, and the percentage of cytoplasmic c-myc-positive cells were independent prognostic parameters. Bcl-2 expression did not correlate with clinical outcome. The Mib-1 index correlated with the presence of epithelioid cells (P < 0.03) and the presence of apoptotic bodies (P < 0.001) and c-myc. A strong inverse relationship was found between (nuclear and cytoplasmic) c-myc and Bcl-2 (P < 0.00004 and P < 0.006, respectively), suggesting that Bcl-2 cooperates with c-myc to immortalize uveal melanoma cells. Images Figure 1 Figure 2 PMID:7573354

Novel, improved grading system(s) for IDH-mutant astrocytic gliomas.

PubMed

Shirahata, Mitsuaki; Ono, Takahiro; Stichel, Damian; Schrimpf, Daniel; Reuss, David E; Sahm, Felix; Koelsche, Christian; Wefers, Annika; Reinhardt, Annekathrin; Huang, Kristin; Sievers, Philipp; Shimizu, Hiroaki; Nanjo, Hiroshi; Kobayashi, Yusuke; Miyake, Yohei; Suzuki, Tomonari; Adachi, Jun-Ichi; Mishima, Kazuhiko; Sasaki, Atsushi; Nishikawa, Ryo; Bewerunge-Hudler, Melanie; Ryzhova, Marina; Absalyamova, Oksana; Golanov, Andrey; Sinn, Peter; Platten, Michael; Jungk, Christine; Winkler, Frank; Wick, Antje; Hänggi, Daniel; Unterberg, Andreas; Pfister, Stefan M; Jones, David T W; van den Bent, Martin; Hegi, Monika; French, Pim; Baumert, Brigitta G; Stupp, Roger; Gorlia, Thierry; Weller, Michael; Capper, David; Korshunov, Andrey; Herold-Mende, Christel; Wick, Wolfgang; Louis, David N; von Deimling, Andreas

2018-04-23

According to the 2016 World Health Organization Classification of Tumors of the Central Nervous System (2016 CNS WHO), IDH-mutant astrocytic gliomas comprised WHO grade II diffuse astrocytoma, IDH-mutant (AII IDHmut ), WHO grade III anaplastic astrocytoma, IDH-mutant (AAIII IDHmut ), and WHO grade IV glioblastoma, IDH-mutant (GBM IDHmut ). Notably, IDH gene status has been made the major criterion for classification while the manner of grading has remained unchanged: it is based on histological criteria that arose from studies which antedated knowledge of the importance of IDH status in diffuse astrocytic tumor prognostic assessment. Several studies have now demonstrated that the anticipated differences in survival between the newly defined AII IDHmut and AAIII IDHmut have lost their significance. In contrast, GBM IDHmut still exhibits a significantly worse outcome than its lower grade IDH-mutant counterparts. To address the problem of establishing prognostically significant grading for IDH-mutant astrocytic gliomas in the IDH era, we undertook a comprehensive study that included assessment of histological and genetic approaches to prognosis in these tumors. A discovery cohort of 211 IDH-mutant astrocytic gliomas with an extended observation was subjected to histological review, image analysis, and DNA methylation studies. Tumor group-specific methylation profiles and copy number variation (CNV) profiles were established for all gliomas. Algorithms for automated CNV analysis were developed. All tumors exhibiting 1p/19q codeletion were excluded from the series. We developed algorithms for grading, based on molecular, morphological and clinical data. Performance of these algorithms was compared with that of WHO grading. Three independent cohorts of 108, 154 and 224 IDH-mutant astrocytic gliomas were used to validate this approach. In the discovery cohort several molecular and clinical parameters were of prognostic relevance. Most relevant for overall survival (OS) was CDKN2A/B homozygous deletion. Other parameters with major influence were necrosis and the total number of CNV. Proliferation as assessed by mitotic count, which is a key parameter in 2016 CNS WHO grading, was of only minor influence. Employing the parameters most relevant for OS in our discovery set, we developed two models for grading these tumors. These models performed significantly better than WHO grading in both the discovery and the validation sets. Our novel algorithms for grading IDH-mutant astrocytic gliomas overcome the challenges caused by introduction of IDH status into the WHO classification of diffuse astrocytic tumors. We propose that these revised approaches be used for grading of these tumors and incorporated into future WHO criteria.

Expression of plakophilin 3 in diffuse malignant pleural mesothelioma.

PubMed

Mašić, Silvija; Brčić, Luka; Krušlin, Božo; Šepac, Ana; Pigac, Biserka; Stančić-Rokotov, Dinko; Jakopović, Marko; Seiwerth, Sven

2018-05-03

Diffuse malignant pleural mesothelioma (DMPM) is the most common primary malignant pleural neoplasm still posing major diagnostic, prognostic and therapeutic challenges. Plakophilins are structural proteins considered to be important for cell stability and adhesion in both tumor and normal tissues. Plakophilin 3 is a protein present in desmosomes of stratified and simple epithelia of normal tissues with presence in malignant cells of various tumors where it participates in the process of tumorigenesis. The aim of this study was to investigate the expression of plakophilin 3 protein in DMPM, but also to study its prognostic significance and relation to histologically accessible parameters of aggressive growth. Archival samples of tissue with established diagnosis of DMPM and samples of normal pleural tissue were used. Tumor samples were classified into three histological types of DMPM (epithelioid, sarcomatoid and biphasic). Additional subclassification of epithelioid mesotheliomas into nine patterns based on the prevalent histological component of the tumor was then performed. After immunohistochemical staining, cytoplasmic and membrane immunopositivity of tumor cells was assesed by scoring the intensity of the staining from 0 (no staining) to 4 (very strong staining). Prognostic value and expression of plakophilin 3 with consideration to histologically estimated aggression in tumor growth were then statistically analyzed using non- parametric tests. The results demonstrated higher level of plakophilin 3 expression in tumor samples with histologically more aggressive tumor growth, but no significant prognostic value. According to our study, plakophilin 3 appears to be involved in tumor invasion in malignant mesothelioma.

Prognostic value of fluorine-18 fludeoxyglucose positron emission tomography parameters differs according to primary tumour location in small-cell lung cancer.

PubMed

Nobashi, Tomomi; Koyasu, Sho; Nakamoto, Yuji; Kubo, Takeshi; Ishimori, Takayoshi; Kim, Young H; Yoshizawa, Akihiko; Togashi, Kaori

2016-01-01

To investigate the prognostic value of fluorine-18 fludeoxyglucose (FDG) positron emission tomography (PET) parameters for small-cell lung cancer (SCLC), according to the primary tumour location, adjusted by conventional prognostic factors. From 2008 to 2013, we enrolled consecutive patients with histologically proven SCLC, who had undergone FDG-PET/CT prior to initial therapy. The primary tumour location was categorized into central or peripheral types. PET parameters and clinical variables were evaluated using univariate and multivariate analysis. A total of 69 patients were enrolled in this study; 28 of these patients were categorized as having the central type and 41 patients as having the peripheral type. In univariate analysis, stage, serum neuron-specific enolase, whole-body metabolic tumour volume (WB-MTV) and whole-body total lesion glycolysis (WB-TLG) were found to be significant in both types of patients. In multivariate analysis, the independent prognostic factor was found to be stage in the central type, but WB-MTV and WB-TLG in the peripheral type. Kaplan-Meier analysis demonstrated that patients with peripheral type with limited disease and low WB-MTV or WB-TLG showed significantly better overall survival than all of the other groups (p < 0.0083). The FDG-PET volumetric parameters were demonstrated to be significant and independent prognostic factors in patients with peripheral type of SCLC, while stage was the only independent prognostic factor in patients with central type of SCLC. FDG-PET is a non-invasive method that could potentially be used to estimate the prognosis of patients, especially those with peripheral-type SCLC.

Predictive value of pretreatment positron emission tomography/computed tomography in patients with newly diagnosed extranodal natural killer/T-cell lymphoma.

PubMed

Bai, Bing; Huang, Hui-Qiang; Cai, Qi-Chun; Fan, Wei; Wang, Xiao-Xiao; Zhang, Xu; Lin, Ze-Xiao; Gao, Yan; Xia, Yun-Fei; Guo, Ying; Cai, Qing-Qing; Jiang, Wen-Qi; Lin, Tong-Yu

2013-03-01

The role of (18)Fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) in extranodal natural killer/T-cell lymphoma (ENKL) is not well established. This study aimed to investigate the prognostic role of the pretreatment maximum standardized uptake value (SUV(max)) on PET/CT in patients with newly diagnosed ENKL. Among 364 consecutive patients with newly diagnosed ENKL, 81 patients were included and reviewed. The impact of SUV(max) on survival and the relationship between SUV(max) and other clinicopathological parameters were analyzed. The median SUV(max) was 14.6 (range 2.0-45.4). The optimal cutoff value of SUV(max) to predict overall survival (OS) was 15. Patients with high SUV(max) (SUVmax >15) were associated with bulky disease (P < 0.001), local invasion (P = 0.030), high score of Korean Prognostic Index (KPI, P = 0.046), resistance to primary treatment (P = 0.014), poor OS (P < 0.001), and unfavorable progression-free survival (P < 0.001). With a median follow-up of 25.0 months, the median OS was 63.0 months (range 2.0-99.0 months). Multivariate analyses revealed the following independent prognostic factors for OS: age >60 years (P = 0.001), stage III-IV (P = 0.023), SUV(max) >15 (P = 0.020), and bulky disease (>5 cm) (P = 0.002). By using the SUV(max), patients in most subgroups stratified by the KPI or the International Prognostic Index (IPI) were further discriminated in OS with significant statistical difference. Our results suggest the pretreatment SUV(max) is predictive of prognosis in patients with newly diagnosed ENKL. The SUV(max) may provide additional prognostic information for IPI and KPI.

Bimodality of intratumor Ki67 expression is an independent prognostic factor of overall survival in patients with invasive breast carcinoma.

PubMed

Laurinavicius, Arvydas; Plancoulaine, Benoit; Rasmusson, Allan; Besusparis, Justinas; Augulis, Renaldas; Meskauskas, Raimundas; Herlin, Paulette; Laurinaviciene, Aida; Abdelhadi Muftah, Abir A; Miligy, Islam; Aleskandarany, Mohammed; Rakha, Emad A; Green, Andrew R; Ellis, Ian O

2016-04-01

Proliferative activity, assessed by Ki67 immunohistochemistry (IHC), is an established prognostic and predictive biomarker of breast cancer (BC). However, it remains under-utilized due to lack of standardized robust measurement methodologies and significant intratumor heterogeneity of expression. A recently proposed methodology for IHC biomarker assessment in whole slide images (WSI), based on systematic subsampling of tissue information extracted by digital image analysis (DIA) into hexagonal tiling arrays, enables computation of a comprehensive set of Ki67 indicators, including intratumor variability. In this study, the tiling methodology was applied to assess Ki67 expression in WSI of 152 surgically removed Ki67-stained (on full-face sections) BC specimens and to test which, if any, Ki67 indicators can predict overall survival (OS). Visual Ki67 IHC estimates and conventional clinico-pathologic parameters were also included in the study. Analysis revealed linearly independent intrinsic factors of the Ki67 IHC variance: proliferation (level of expression), disordered texture (entropy), tumor size and Nottingham Prognostic Index, bimodality, and correlation. All visual and DIA-generated indicators of the level of Ki67 expression provided significant cutoff values as single predictors of OS. However, only bimodality indicators (Ashman's D, in particular) were independent predictors of OS in the context of hormone receptor and HER2 status. From this, we conclude that spatial heterogeneity of proliferative tumor activity, measured by DIA of Ki67 IHC expression and analyzed by the hexagonal tiling approach, can serve as an independent prognostic indicator of OS in BC patients that outperforms the prognostic power of the level of proliferative activity.

Heart failure and anemia: Effects on prognostic variables.

PubMed

Cattadori, Gaia; Agostoni, Piergiuseppe; Corrà, Ugo; Sinagra, Gianfranco; Veglia, Fabrizio; Salvioni, Elisabetta; Bonomi, Alice; La Gioia, Rocco; Scardovi, Angela B; Ferraironi, Alessandro; Emdin, Michele; Metra, Marco; Di Lenarda, Andrea; Limongelli, Giuseppe; Raimondo, Rosa; Re, Federica; Guazzi, Marco; Belardinelli, Romualdo; Parati, Gianfranco; Caravita, Sergio; Magrì, Damiano; Lombardi, Carlo; Frigerio, Maria; Oliva, Fabrizio; Girola, Davide; Mezzani, Alessandro; Farina, Stefania; Mapelli, Massimo; Scrutinio, Domenico; Pacileo, Giuseppe; Apostolo, Anna; Iorio, AnnaMaria; Paolillo, Stefania; Filardi, Pasquale Perrone; Gargiulo, Paola; Bussotti, Maurizio; Marchese, Giovanni; Correale, Michele; Badagliacca, Roberto; Sciomer, Susanna; Palermo, Pietro; Contini, Mauro; Giannuzzi, Pantaleo; Battaia, Elisa; Cicoira, Mariantonietta; Clemenza, Francesco; Minà, Chiara; Binno, Simone; Passino, Claudio; Piepoli, Massimo F

2017-01-01

Anemia is frequent in heart failure (HF), and it is associated with higher mortality. The predictive power of established HF prognostic parameters in anemic HF patients is unknown. Clinical, laboratory, echocardiographic and cardiopulmonary-exercise-test (CPET) data were analyzed in 3913 HF patients grouped according to hemoglobin (Hb) values. 248 (6%), 857 (22%), 2160 (55%) and 648 (17%) patients had very low (<11g/dL), low (11-12 for females, 11-13 for males), normal (12-15 for females, 13-15 for males) and high (>15) Hb, respectively. Median follow-up was 1363days (606-1883). CPETs were always performed safely. Hb was related to prognosis (Hazard ratio (HR)=0.864). No prognostic difference was observed between normal and high Hb groups. Peak oxygen consumption (VO 2 ), ventilatory efficiency (VE/VCO 2 slope), plasma sodium concentration, ejection fraction (LVEF), kidney function and Hb were independently related to prognosis in the entire population. Considering Hb groups separately, peakVO 2 (very low Hb HR=0.549, low Hb HR=0.613, normal Hb HR=0.618, high Hb HR=0.542) and LVEF (very low Hb HR=0.49, low Hb HR=0.692, normal Hb HR=0.697, high Hb HR=0.694) maintained their prognostic roles. High VE/VCO 2 slope was associated with poor prognosis only in patients with low and normal Hb. Anemic HF patients have a worse prognosis, but CPET can be safely performed. PeakVO 2 and LVEF, but not VE/VCO 2 slope, maintain their prognostic power also in HF patients with Hb<11g/dL, suggesting CPET use and a multiparametric approach in HF patients with low Hb. However, the prognostic effect of an anemia-oriented follow-up is unknown. Copyright © 2016 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Prognostic factors for acute myeloid leukaemia in adults--biological significance and clinical use.

PubMed

Liersch, Ruediger; Müller-Tidow, Carsten; Berdel, Wolfgang E; Krug, Utz

2014-04-01

Acute myeloid leukaemia (AML) is a heterogeneous disease. Prognosis of AML is influenced both by patient-specific as well as disease-specific factors. Age is the most prominent patient-specific risk factor, while chromosomal aberrations are the strongest disease-specific risk factors. For patients with cytogenetically normal AML, prognosis can be specified by mutational status of the genes NPM1, FLT3 and CEBPA. A growing number of recurrent mutations in additional genes have recently been identified, for which the prognostic effect yet has to be determined. Performance status, geriatric assessment, secondary leukaemia following myelodysplastic syndrome or cytotoxic treatment, common laboratory parameters, leukaemic stem cell frequency, bone marrow microenvironment, gene expression levels, epigenetic changes, micro-RNA's as well as kinetics and depth of response to treatment influence prognosis of AML patients. Despite the high number of established risk factors, only few predictive markers exist which can truly aid therapy decisions in patients with AML. © 2014 John Wiley & Sons Ltd.

Prognostics of slurry pumps based on a moving-average wear degradation index and a general sequential Monte Carlo method

NASA Astrophysics Data System (ADS)

Wang, Dong; Tse, Peter W.

2015-05-01

Slurry pumps are commonly used in oil-sand mining for pumping mixtures of abrasive liquids and solids. These operations cause constant wear of slurry pump impellers, which results in the breakdown of the slurry pumps. This paper develops a prognostic method for estimating remaining useful life of slurry pump impellers. First, a moving-average wear degradation index is proposed to assess the performance degradation of the slurry pump impeller. Secondly, the state space model of the proposed health index is constructed. A general sequential Monte Carlo method is employed to derive the parameters of the state space model. The remaining useful life of the slurry pump impeller is estimated by extrapolating the established state space model to a specified alert threshold. Data collected from an industrial oil sand pump were used to validate the developed method. The results show that the accuracy of the developed method improves as more data become available.

Early response to therapy and survival in multiple myeloma.

PubMed

Schaar, C G; Kluin-Nelemans, J C; le Cessie, S; Franck, P F H; te Marvelde, M C; Wijermans, P W

2004-04-01

Whether the response to chemotherapy is a prognosticator in multiple myeloma (MM) is still not known. Therefore, the relationship between survival and the rate of monoclonal protein (M-protein) decrement during the first cycles of therapy was prospectively assessed in 262 patients with newly diagnosed MM that were included in a phase III trial (HOVON-16). M-proteins were collected monthly during melphalan-prednisone therapy (MP: melphalan 0.25 mg/kg, prednisone 1.0 mg/kg orally for 5 d every 4 weeks). Patients with light chain disease (n = 18), immunoglobulin M (IgM)-MM (n = 1) and no immunotyping (n = 1) were excluded. Of the 242 patients studied, 75% had IgG M-protein and 25% IgA; MM stages: I: 1%, II: 35% and III: 64%. The median M-protein decrease after the first cycle of MP was 21% for IgG and 27% for IgA, and declined to < 5% after four cycles. An obvious survival advantage was seen for patients who had an M-protein decrease of at least 30% after the first MP cycle, which became significant when an M-protein decrease of 40% or more was reached. As established prognostic parameters (Salmon & Durie stage, serum creatinine, and haemoglobin) also remained prognostically significant, we concluded that early response to MP predicts for survival in MM.

A new extranodal scoring system based on the prognostically relevant extranodal sites in diffuse large B-cell lymphoma, not otherwise specified treated with chemoimmunotherapy.

PubMed

Hwang, Hee Sang; Yoon, Dok Hyun; Suh, Cheolwon; Huh, Jooryung

2016-08-01

Extranodal involvement is a well-known prognostic factor in patients with diffuse large B-cell lymphomas (DLBCL). Nevertheless, the prognostic impact of the extranodal scoring system included in the conventional international prognostic index (IPI) has been questioned in an era where rituximab treatment has become widespread. We investigated the prognostic impacts of individual sites of extranodal involvement in 761 patients with DLBCL who received rituximab-based chemoimmunotherapy. Subsequently, we established a new extranodal scoring system based on extranodal sites, showing significant prognostic correlation, and compared this system with conventional scoring systems, such as the IPI and the National Comprehensive Cancer Network-IPI (NCCN-IPI). An internal validation procedure, using bootstrapped samples, was also performed for both univariate and multivariate models. Using multivariate analysis with a backward variable selection, we found nine extranodal sites (the liver, lung, spleen, central nervous system, bone marrow, kidney, skin, adrenal glands, and peritoneum) that remained significant for use in the final model. Our newly established extranodal scoring system, based on these sites, was better correlated with patient survival than standard scoring systems, such as the IPI and the NCCN-IPI. Internal validation by bootstrapping demonstrated an improvement in model performance of our modified extranodal scoring system. Our new extranodal scoring system, based on the prognostically relevant sites, may improve the performance of conventional prognostic models of DLBCL in the rituximab era and warrants further external validation using large study populations.

Establishment and Validation of GV-SAPS II Scoring System for Non-Diabetic Critically Ill Patients

PubMed Central

Liu, Wen-Yue; Lin, Shi-Gang; Zhu, Gui-Qi; Poucke, Sven Van; Braddock, Martin; Zhang, Zhongheng; Mao, Zhi; Shen, Fei-Xia

2016-01-01

Background and Aims Recently, glucose variability (GV) has been reported as an independent risk factor for mortality in non-diabetic critically ill patients. However, GV is not incorporated in any severity scoring system for critically ill patients currently. The aim of this study was to establish and validate a modified Simplified Acute Physiology Score II scoring system (SAPS II), integrated with GV parameters and named GV-SAPS II, specifically for non-diabetic critically ill patients to predict short-term and long-term mortality. Methods Training and validation cohorts were exacted from the Multiparameter Intelligent Monitoring in Intensive Care database III version 1.3 (MIMIC-III v1.3). The GV-SAPS II score was constructed by Cox proportional hazard regression analysis and compared with the original SAPS II, Sepsis-related Organ Failure Assessment Score (SOFA) and Elixhauser scoring systems using area under the curve of the receiver operator characteristic (auROC) curve. Results 4,895 and 5,048 eligible individuals were included in the training and validation cohorts, respectively. The GV-SAPS II score was established with four independent risk factors, including hyperglycemia, hypoglycemia, standard deviation of blood glucose levels (GluSD), and SAPS II score. In the validation cohort, the auROC values of the new scoring system were 0.824 (95% CI: 0.813–0.834, P< 0.001) and 0.738 (95% CI: 0.725–0.750, P< 0.001), respectively for 30 days and 9 months, which were significantly higher than other models used in our study (all P < 0.001). Moreover, Kaplan-Meier plots demonstrated significantly worse outcomes in higher GV-SAPS II score groups both for 30-day and 9-month mortality endpoints (all P< 0.001). Conclusions We established and validated a modified prognostic scoring system that integrated glucose variability for non-diabetic critically ill patients, named GV-SAPS II. It demonstrated a superior prognostic capability and may be an optimal scoring system for prognostic evaluation in this patient group. PMID:27824941

A novel prediction method about single components of analog circuits based on complex field modeling.

PubMed

Zhou, Jingyu; Tian, Shulin; Yang, Chenglin

2014-01-01

Few researches pay attention to prediction about analog circuits. The few methods lack the correlation with circuit analysis during extracting and calculating features so that FI (fault indicator) calculation often lack rationality, thus affecting prognostic performance. To solve the above problem, this paper proposes a novel prediction method about single components of analog circuits based on complex field modeling. Aiming at the feature that faults of single components hold the largest number in analog circuits, the method starts with circuit structure, analyzes transfer function of circuits, and implements complex field modeling. Then, by an established parameter scanning model related to complex field, it analyzes the relationship between parameter variation and degeneration of single components in the model in order to obtain a more reasonable FI feature set via calculation. According to the obtained FI feature set, it establishes a novel model about degeneration trend of analog circuits' single components. At last, it uses particle filter (PF) to update parameters for the model and predicts remaining useful performance (RUP) of analog circuits' single components. Since calculation about the FI feature set is more reasonable, accuracy of prediction is improved to some extent. Finally, the foregoing conclusions are verified by experiments.

Beta-blockers influence the short-term and long-term prognostic information of natriuretic peptides and catecholamines in chronic heart failure independent from specific agents.

PubMed

Frankenstein, Lutz; Nelles, Manfred; Slavutsky, Maxim; Schellberg, Dieter; Doesch, Andreas; Katus, Hugo; Remppis, Andrew; Zugck, Christian

2007-10-01

In chronic heart failure (CHF), the physiologic effects of natriuretic peptides and catecholamines are interdependent. Furthermore, reports state an agent-dependent effect of individual beta-blockers on biomarkers. Data on the short-term and long-term predictive power comparing these biomarkers as well as accounting for the influence of beta-blocker treatment both on the marker or the resultant prognostic information are scarce. We included 513 consecutive patients with systolic CHF, measured atrial natriuretic peptide (ANP), N-terminal prohormone brain natriuretic peptide (NTproBNP), noradrenaline, and adrenaline, and monitored them for 90 +/- 25 months. Death or the combination of death and cardiac transplantation at 1 year, 5 years, and overall follow-up were considered end points. Compared with patients not taking beta-blockers, patients taking beta-blockers had significantly lower levels of catecholamines but not natriuretic peptides. Only for adrenaline was the amount of this effect related to the specific beta-blocker chosen. Receiver operating characteristic curves demonstrated superior prognostic accuracy for NTproBNP both at the 1- and 5-year follow-up compared with ANP, noradrenaline, and adrenaline. In multivariate analysis including established risk markers (New York Heart Association functional class, left ventricular ejection fraction, peak oxygen uptake, and 6-minute walk test), of all neurohumoral parameters, only NTproBNP remained an independent predictor for both end points. Long-term beta-blocker therapy is associated with decreased levels of plasma catecholamines but not natriuretic peptides. This effect is independent from the actual beta-blocker chosen for natriuretic peptides and noradrenaline. In multivariate analysis, both for short-term and long-term prediction of mortality or the combined end point of death and cardiac transplantation, only NTproBNP remained independent from established clinical risk markers.

Multiple Damage Progression Paths in Model-Based Prognostics

NASA Technical Reports Server (NTRS)

Daigle, Matthew; Goebel, Kai Frank

2011-01-01

Model-based prognostics approaches employ domain knowledge about a system, its components, and how they fail through the use of physics-based models. Component wear is driven by several different degradation phenomena, each resulting in their own damage progression path, overlapping to contribute to the overall degradation of the component. We develop a model-based prognostics methodology using particle filters, in which the problem of characterizing multiple damage progression paths is cast as a joint state-parameter estimation problem. The estimate is represented as a probability distribution, allowing the prediction of end of life and remaining useful life within a probabilistic framework that supports uncertainty management. We also develop a novel variance control mechanism that maintains an uncertainty bound around the hidden parameters to limit the amount of estimation uncertainty and, consequently, reduce prediction uncertainty. We construct a detailed physics-based model of a centrifugal pump, to which we apply our model-based prognostics algorithms. We illustrate the operation of the prognostic solution with a number of simulation-based experiments and demonstrate the performance of the chosen approach when multiple damage mechanisms are active

Bayesian Framework Approach for Prognostic Studies in Electrolytic Capacitor under Thermal Overstress Conditions

DTIC Science & Technology

2012-09-01

make end of life ( EOL ) and remaining useful life (RUL) estimations. Model-based prognostics approaches perform these tasks with the help of first...in parameters Degradation Modeling Parameter estimation Prediction Thermal / Electrical Stress Experimental Data State Space model RUL EOL ...distribution at given single time point kP , and use this for multi-step predictions to EOL . There are several methods which exits for selecting the sigma

Rectal cancer delivery of radiotherapy in adequate time and with adequate dose is influenced by treatment center, treatment schedule, and gender and is prognostic parameter for local control: Results of study CAO/ARO/AIO-94

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fietkau, Rainer; Roedel, Claus; Hohenberger, Werner

2007-03-15

Purpose: The impact of the delivery of radiotherapy (RT) on treatment results in rectal cancer patients is unknown. Methods and Materials: The data from 788 patients with rectal cancer treated within the German CAO/AIO/ARO-94 phase III trial were analyzed concerning the impact of the delivery of RT (adequate RT: minimal radiation RT dose delivered, 4300 cGy for neoadjuvant RT or 4700 cGy for adjuvant RT; completion of RT in <44 days for neoadjuvant RT or <49 days for adjuvant RT) in different centers on the locoregional recurrence rate (LRR) and disease-free survival (DFS) at 5 years. The LRR, DFS, andmore » delivery of RT were analyzed as endpoints in multivariate analysis. Results: A significant difference was found between the centers and the delivery of RT. The overall delivery of RT was a prognostic factor for the LRR (no RT, 29.6% {+-} 7.8%; inadequate RT, 21.2% {+-} 5.6%; adequate RT, 6.8% {+-} 1.4%; p = 0.0001) and DFS (no RT, 55.1% {+-} 9.1%; inadequate RT, 57.4% {+-} 6.3%; adequate RT, 69.1% {+-} 2.3%; p = 0.02). Postoperatively, delivery of RT was a prognostic factor for LRR on multivariate analysis (together with pathologic stage) but not for DFS (independent parameters, pathologic stage and age). Preoperatively, on multivariate analysis, pathologic stage, but not delivery of RT, was an independent prognostic parameter for LRR and DFS (together with adequate chemotherapy). On multivariate analysis, the treatment center, treatment schedule (neoadjuvant vs. adjuvant RT), and gender were prognostic parameters for adequate RT. Conclusion: Delivery of RT should be regarded as a prognostic factor for LRR in rectal cancer and is influenced by the treatment center, treatment schedule, and patient gender.« less

A novel gene expression-based prognostic scoring system to predict survival in gastric cancer

DOE PAGES

Wang, Pin; Wang, Yunshan; Hang, Bo; ...

2016-07-11

Analysis of gene expression patterns in gastric cancer (GC) can help to identify a comprehensive panel of gene biomarkers for predicting clinical outcomes and to discover potential new therapeutic targets. Here, a multi-step bioinformatics analytic approach was developed to establish a novel prognostic scoring system for GC. We first identified 276 genes that were robustly differentially expressed between normal and GC tissues, of which, 249 were found to be significantly associated with overall survival (OS) by univariate Cox regression analysis. The biological functions of 249 genes are related to cell cycle, RNA/ncRNA process, acetylation and extracellular matrix organization. A networkmore » was generated for view of the gene expression architecture of 249 genes in 265 GCs. Finally, we applied a canonical discriminant analysis approach to identify a 53-gene signature and a prognostic scoring system was established based on a canonical discriminant function of 53 genes. The prognostic scores strongly predicted patients with GC to have either a poor or good OS. Our study raises the prospect that the practicality of GC patient prognosis can be assessed by this prognostic scoring system.« less

A novel gene expression-based prognostic scoring system to predict survival in gastric cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Pin; Wang, Yunshan; Hang, Bo

Analysis of gene expression patterns in gastric cancer (GC) can help to identify a comprehensive panel of gene biomarkers for predicting clinical outcomes and to discover potential new therapeutic targets. Here, a multi-step bioinformatics analytic approach was developed to establish a novel prognostic scoring system for GC. We first identified 276 genes that were robustly differentially expressed between normal and GC tissues, of which, 249 were found to be significantly associated with overall survival (OS) by univariate Cox regression analysis. The biological functions of 249 genes are related to cell cycle, RNA/ncRNA process, acetylation and extracellular matrix organization. A networkmore » was generated for view of the gene expression architecture of 249 genes in 265 GCs. Finally, we applied a canonical discriminant analysis approach to identify a 53-gene signature and a prognostic scoring system was established based on a canonical discriminant function of 53 genes. The prognostic scores strongly predicted patients with GC to have either a poor or good OS. Our study raises the prospect that the practicality of GC patient prognosis can be assessed by this prognostic scoring system.« less

Gastric lymphomas in Turkey. Analysis of prognostic factors with special emphasis on flow cytometric DNA content.

PubMed

Aydin, Z D; Barista, I; Canpinar, H; Sungur, A; Tekuzman, G

2000-07-01

In contrast to DNA ploidy, to the authors' knowledge the prognostic significance of S-phase fraction (SPF) in gastric lymphomas has not been determined. In the current study, the prognostic significance of various parameters including SPF and DNA aneuploidy were analyzed and some distinct epidemiologic and biologic features of gastric lymphomas in Turkey were found. A series of 78 gastric lymphoma patients followed at Hacettepe University is reported. DNA flow cytometry was performed for 34 patients. The influence of various parameters on survival was investigated with the log rank test. The Cox proportional hazards model was fitted to identify independent prognostic factors. The median age of the patients was 50 years. There was no correlation between patient age and tumor grade. DNA content analysis revealed 4 of the 34 cases to be aneuploid with DNA index values < 1.0. The mean SPF was 33.5%. In the univariate analysis, surgical resection of the tumor, modified Ann Arbor stage, performance status, response to first-line chemotherapy, lactate dehydrogenase (LDH) level, and SPF were important prognostic factors for disease free survival (DFS). The same parameters, excluding LDH level, were important for determining overall survival (OS). In the multivariate analysis, surgical resection of the tumor, disease stage, performance status, and age were found to be important prognostic factors for OS. To the authors' knowledge the current study is the first to demonstrate the prognostic significance of SPF in gastric lymphomas. The distinguishing features of Turkish gastric lymphoma patients are 1) DNA indices of aneuploid cases that all are < 1.0, which is a unique feature; 2) a lower percentage of aneuploid cases; 3) a higher SPF; 4) a younger age distribution; and 5) lack of an age-grade correlation. The authors conclude that gastric lymphomas in Turkey have distinct biologic and epidemiologic characteristics. Copyright 2000 American Cancer Society.

Incorporation of p-53 mutation status and Ki-67 proliferating index in classifying Her2-neu positive gastric adenocarcinoma.

PubMed

Ahmed, Ayesha; Al-Tamimi, Dalal M

2018-12-01

Her2-neu overexpression has a pathogenetic, therapeutic and a controversial prognostic role in gastric cancer. p-53 mutation status and Ki-67 proliferation index are established prognostic markers in many tumors. In this study we evaluated p-53 and Ki-67 in relation to Her2-neu positive and negative gastric adenocarcinoma (GA). This cross-sectional study was carried out at King Fahd Hospital of Imam Abdulrahman bin Faisal University. Fifty cases of GA were retrieved from pathology archives. Clinico-pathological parameters were evaluated. Immunohistochemical protein analysis for Her2-neu, Ki-67 and p-53 was carried out. Fluorescent in situ hybridization (FISH) analysis was done for Her2-neu positive cases showing 2+ immunoexpression. Frequency of Ki-67 and p-53 positivity in Her2-neu positive cases was calculated and compared with those in Her2-neu negative cases. Correlation of clinicopatological parameters with Her2 positive and negative cases, p-53 mutation status and Ki-67 proliferation index was carried out. Her2-neu overexpression was present in 12% (n = 6) cases. A high Ki-67 was seen predominantly in Her2-neu positive cases (83%, n = 5). Her2-neu negative cases (n = 44) showed moderate (31.88%, n = 14) to low (34%, n = 15) Ki-67. Diffuse p-53 positivity was seen predominantly in Her2-neu positive cases (33.33%, n = 2). Focal p-53 was seen mainly in Her2-neu negative cases 56.8% (n = 25). Negative p-53 was seen to be independent of Her2-neu status. Her2-neu positivity is strongly associated with diffuse p-53 mutation status and high Ki-67 proliferation. Her 2-neu negative status is associated with focal p-53 positivity and low to moderate Ki-67 proliferation index. Such stratifications in prognostic markers could not only be predictive in patient's prognostics but could also form a basis of molecular classification of gastric cancer.

The prognostic significance of the 2014 International Society of Urological Pathology (ISUP) grading system for prostate cancer.

PubMed

Samaratunga, Hemamali; Delahunt, Brett; Gianduzzo, Troy; Coughlin, Geoff; Duffy, David; LeFevre, Ian; Johannsen, Shulammite; Egevad, Lars; Yaxley, John

2015-10-01

The 2005 International Society of Urological Pathology (ISUP) modified Gleason grading system was further amended in 2014 with the establishment of grade groupings (ISUP grading). This study examined the predictive value of ISUP grading, comparing results with recognised prognostic parameters.Of 3700 men undergoing radical prostatectomy (RP) reported at Aquesta Pathology between 2008 and 2013, 2079 also had a positive needle biopsy available for review. We examined the association between needle biopsy 2014 ISUP grade and 2005 modified Gleason score, tumour volume, pathological stage of the subsequent RP tumour, as well as biochemical recurrence-free survival (BRFS). The median age was 62 (range 32-79 years). Median serum prostate specific antigen was 5.9 (range 0.4-69 ng/mL). For needle biopsies, 280 (13.5%), 1031 (49.6%), 366 (17.6%), 77 (3.7%) and 325 (15.6%) were 2014 ISUP grades 1-5, respectively. Needle biopsy 2014 ISUP grade showed a significant association with RP tumour volume (p < 0.001), TNM pT and N stage (p < 0.001) and BRFS (p < 0.001). Multivariate analysis using Cox proportional hazards regression model showed serum prostate specific antigen (PSA) at the time of diagnosis and ISUP grade >2 to be significantly associated with BRFS.This study provides evidence of the prognostic significance of ISUP grading for thin core needle biopsy of prostate.

Management of heart failure in the new era: the role of scores.

PubMed

Mantegazza, Valentina; Badagliacca, Roberto; Nodari, Savina; Parati, Gianfranco; Lombardi, Carolina; Di Somma, Salvatore; Carluccio, Erberto; Dini, Frank Lloyd; Correale, Michele; Magrì, Damiano; Agostoni, Piergiuseppe

2016-08-01

Heart failure is a widespread syndrome involving several organs, still characterized by high mortality and morbidity, and whose clinical course is heterogeneous and hardly predictable.In this scenario, the assessment of heart failure prognosis represents a fundamental step in clinical practice. A single parameter is always unable to provide a very precise prognosis. Therefore, risk scores based on multiple parameters have been introduced, but their clinical utility is still modest. In this review, we evaluated several prognostic models for acute, right, chronic, and end-stage heart failure based on multiple parameters. In particular, for chronic heart failure we considered risk scores essentially based on clinical evaluation, comorbidities analysis, baroreflex sensitivity, heart rate variability, sleep disorders, laboratory tests, echocardiographic imaging, and cardiopulmonary exercise test parameters. What is at present established is that a single parameter is not sufficient for an accurate prediction of prognosis in heart failure because of the complex nature of the disease. However, none of the scoring systems available is widely used, being in some cases complex, not user-friendly, or based on expensive or not easily available parameters. We believe that multiparametric scores for risk assessment in heart failure are promising but their widespread use needs to be experienced.

A Novel Prediction Method about Single Components of Analog Circuits Based on Complex Field Modeling

PubMed Central

Tian, Shulin; Yang, Chenglin

2014-01-01

Few researches pay attention to prediction about analog circuits. The few methods lack the correlation with circuit analysis during extracting and calculating features so that FI (fault indicator) calculation often lack rationality, thus affecting prognostic performance. To solve the above problem, this paper proposes a novel prediction method about single components of analog circuits based on complex field modeling. Aiming at the feature that faults of single components hold the largest number in analog circuits, the method starts with circuit structure, analyzes transfer function of circuits, and implements complex field modeling. Then, by an established parameter scanning model related to complex field, it analyzes the relationship between parameter variation and degeneration of single components in the model in order to obtain a more reasonable FI feature set via calculation. According to the obtained FI feature set, it establishes a novel model about degeneration trend of analog circuits' single components. At last, it uses particle filter (PF) to update parameters for the model and predicts remaining useful performance (RUP) of analog circuits' single components. Since calculation about the FI feature set is more reasonable, accuracy of prediction is improved to some extent. Finally, the foregoing conclusions are verified by experiments. PMID:25147853

Towards Prognostics of Power MOSFETs: Accelerated Aging and Precursors of Failure

NASA Technical Reports Server (NTRS)

Celaya, Jose R.; Saxena, Abhinav; Wysocki, Philip; Saha, Sankalita; Goebel, Kai

2010-01-01

This paper presents research results dealing with power MOSFETs (metal oxide semiconductor field effect transistor) within the prognostics and health management of electronics. Experimental results are presented for the identification of the on-resistance as a precursor to failure of devices with die-attach degradation as a failure mechanism. Devices are aged under power cycling in order to trigger die-attach damage. In situ measurements of key electrical and thermal parameters are collected throughout the aging process and further used for analysis and computation of the on-resistance parameter. Experimental results show that the devices experience die-attach damage and that the on-resistance captures the degradation process in such a way that it could be used for the development of prognostics algorithms (data-driven or physics-based).

Prognostic Significance of Pre-treatment Serum C-Reactive Protein Level in Patients with Adenocarcinoma of the Uterine Cervix.

PubMed

Bodner-Adler, Barbara; Kimberger, Oliver; Schneidinger, Cora; Kölbl, Heinz; Bodner, Klaus

2016-09-01

To evaluate pre-treatment serum C-reactive protein (CRP) level as a prognostic parameter in patients with adenocarcinoma of the uterine cervix. Pre-treatment CRP levels were analyzed to determine potential associations with clinicopathological parameters and to assess prognostic value in 46 patients with sole adenocarcinoma of the uterine cervix. The mean (±SD) pre-treatment serum CRP level was 5.82 (7.21) mg/l. Serum CRP concentration significantly correlated positively with age at diagnosis (p=0.001), lymphovascular space invasion (p=0.0026), recurrent disease (p=0.0001) and International Federation of Gynecology and Obstetrics (FIGO) stage (p=0.0002). In multivariate Cox regression models with age, FIGO stage, histological grade and lymph node status, elevated CRP and cancer antigen 125 levels were associated with shortened survival (p<0.05). Overall 5-year survival rate of patients with pre-treatment serum CRP level <5.0 mg/l was 100% compared to 46.9% for patients with pre-treatment CRP level ≥5.0 mg/l. Serum CRP level can be seen as an additional independent prognostic parameter in patients with the rare histological subtype adenocarcinoma of the uterine cervix. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Current state of prognostication and risk stratification in myelodysplastic syndromes.

PubMed

Zeidan, Amer M; Gore, Steven D; Padron, Eric; Komrokji, Rami S

2015-03-01

Myelodysplastic syndromes (MDS) are characterized by significant biologic and clinical heterogeneity. Because of the wide outcome variability, accurate prognostication is vital to high-quality risk-adaptive care of MDS patients. In this review, we discuss the current state of prognostic schemes for MDS and overview efforts aimed at utilizing molecular aberrations for prognostication in clinical practice. Several prognostic instruments have been developed and validated with increasing accuracy and complexity. Oncologists should be aware of the inherent limitations of these prognostic tools as they counsel patients and make clinical decisions. As more therapies are becoming available for MDS, the focus of model development is shifting from prognostic to treatment-specific predictive instruments. In addition to providing additional prognostic data beyond traditional clinical and pathologic parameters, the improved understanding of the genetic landscape and pathophysiologic consequences in MDS may allow the construction of treatment-specific predictive instruments. How to best use the results of molecular mutation testing to inform clinical decision making in MDS is still a work in progress. Important steps in this direction include standardization in performance and interpretation of assays and better understanding of the independent prognostic importance of the recurrent mutations, especially the less frequent ones.

The ratio of hemoglobin to red cell distribution width as a novel prognostic parameter in esophageal squamous cell carcinoma: a retrospective study from southern China

PubMed Central

Bi, Xiwen; Yang, Hang; An, Xin; Wang, Fenghua; Jiang, Wenqi

2016-01-01

Background We propose a novel prognostic parameter for esophageal squamous cell carcinoma (ESCC)—hemoglobin/red cell distribution width (HB/RDW) ratio. Its clinical prognostic value and relationship with other clinicopathological characteristics were investigated in ESCC patients. Results The optimal cut-off value was 0.989 for the HB/RDW ratio. The HB/RDW ratio (P= 0.035), tumor depth (P = 0.020) and lymph node status (P<0.001) were identified to be an independent prognostic factors of OS by multivariate analysis, which was validated by bootstrap resampling. Patients with a low HB/RDW ratio had a 1.416 times greater risk of dying during follow-up compared with those with a high HB/RDW (95% CI = 1.024–1.958, P = 0.035). Materials and Methods We retrospectively analyzed 362 patients who underwent curative treatment at a single institution between January 2007 and December 2008. The chi-square test was used to evaluate relationships between the HB/RDW ratio and other clinicopathological variables; the Kaplan–Meier method was used to analyze the 5-year overall survival (OS); and the Cox proportional hazards models were used for univariate and multivariate analyses of variables related to OS. Conclusion A significant association was found between the HB/RDW ratio and clinical characteristics and survival outcomes in ESCC patients. Based on these findings, we believe that the HB/RDW ratio is a novel and promising prognostic parameter for ESCC patients. PMID:27223088

Do the conventional clinicopathologic parameters predict for response and survival in head and neck cancer patients undergoing neoadjuvant chemotherapy?

PubMed

Fonseca, E; Cruz, J J; Dueñas, A; Gómez, A; Sánchez, P; Martín, G; Nieto, A; Soria, P; Muñoz, A; Gómez, J L; Pardal, J L

1996-01-01

Neoadjuvant chemotherapy for head and neck carcinoma is still an important treatment modality. The prognostic value of patient and tumor parameters has been extensively evaluated in several trials, yielding mixed results. We report the prognostic factors emerging from a group of patients undergoing neoadjuvant chemotherapy. From April 1986 to June 1992, 149 consecutive patients received cisplatin-5-fluorouracil-based neoadjuvant chemotherapy. After four courses of chemotherapy, patients underwent local-regional treatment with surgery, radiation or both. A variety of patient and tumor characteristics were evaluated as predictors for response to chemotherapy and survival. The complete response, partial response and no response rates to NAC were 52%, 33% and 15%, respectively. No parameters predicted response to chemotherapy. At a maximum follow-up of 87 months, overall survival was 39% and disease-free survival was 49%. Variables shown to be predictors of survival in univariate analyses were age, performance status, histology, site, T, N, stage, and response to chemotherapy. Using the Cox regression analysis, only complete response to induction chemotherapy (P = 0.0006), performance status (P = 0.03), stage (P = 0.01), age (P = 0.03) and primary tumor site (P = 0.04) emerged as independent prognostic factors for survival. Complete response to chemotherapy was confirmed as the strongest prognostic factor influencing survival. However, conventional clinicopathologic factors did not predict response, hence, potential prognostic biologic and molecular factors for response must be sought. At present, much effort must be made for the improvement of the complete response rate, which seems to be a requisite to prolong survival.

Tumor heterogeneity measured on F-18 fluorodeoxyglucose positron emission tomography/computed tomography combined with plasma Epstein-Barr Virus load predicts prognosis in patients with primary nasopharyngeal carcinoma.

PubMed

Chan, Sheng-Chieh; Chang, Kai-Ping; Fang, Yu-Hua Dean; Tsang, Ngan-Ming; Ng, Shu-Hang; Hsu, Cheng-Lung; Liao, Chun-Ta; Yen, Tzu-Chen

2017-01-01

Plasma Epstein-Barr virus (EBV) DNA concentrations predict prognosis in patients with nasopharyngeal carcinoma (NPC). Recent evidence also indicates that intratumor heterogeneity on F-18 fluorodeoxyglucose positron emission tomography ( 18 F-FDG PET) scans is predictive of treatment outcomes in different solid malignancies. Here, we sought to investigate the prognostic value of heterogeneity parameters in patients with primary NPC. Retrospective cohort study. We examined 101 patients with primary NPC who underwent pretreatment 18 F-FDG PET/computed tomography. Circulating levels of EBV DNA were measured in all participants. The following PET heterogeneity parameters were collected: histogram-based heterogeneity parameters, second-order texture features (uniformity, contrast, entropy, homogeneity, dissimilarity, inverse difference moment), and higher-order (coarseness, contrast, busyness, complexity, strength) texture features. The median follow-up time was 5.14 years. Total lesion glycolysis (TLG), tumor heterogeneity measured by histogram-based parameter skewness, and the majority of second-order or higher-order texture features were significantly associated with overall survival (OS) and/or recurrence-free survival (RFS). In multivariate analysis, age (P =.005), EBV DNA load (P = .0002), and uniformity (P = .001) independently predicted OS. Only skewness retained the independent prognostic significance for RFS. Tumor stage, standardized uptake value, or TLG did not show an independent association with survival endpoints. The combination of uniformity, EBV DNA load, and age resulted in a more reliable prognostic stratification (P < .001). Tumor heterogeneity is superior to traditional PET parameters for predicting outcomes in primary NPC. The combination of uniformity with EBV DNA load can improve prognostic stratification in this clinical entity. 4 Laryngoscope, 127:E22-E28, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

Tissue Doppler Imaging in Coronary Artery Diseases and Heart Failure

PubMed Central

Correale, Michele; Totaro, Antonio; Ieva, Riccardo; Ferraretti, Armando; Musaico, Francesco; Biase, Matteo Di

2012-01-01

Recent studies have explored the prognostic role of TDI-derived parameters in major cardiac diseases, such as coronary artery disease (CAD) and heart failure (HF). In these conditions, myocardial mitral annular systolic (S’) and early diastolic (E’) velocities have been shown to predict mortality or cardiovascular events. In heart failure non invasive assessment of LV diastolic pressure by transmitral to mitral annular early diastolic velocity ratio (E/E’) is a strong prognosticator, especially when E/E’ is > or =15. Moreover, other parameters derived by TDI, as cardiac time intervals and Myocardial Performance Index, might play a role in the prognostic stratification in CAD and HF. Recently, a three-dimensional (3-D) TDI imaging modality, triplane TDI, has become available, and this allows calculation of 3-Dvolumes and LV ejection fraction. We present a brief update of TDI. PMID:22845815

Incorporating prognostic imaging biomarkers into clinical practice

PubMed Central

Miles, Kenneth A.

2013-01-01

Abstract A prognostic imaging biomarker can be defined as an imaging characteristic that is objectively measurable and provides information on the likely outcome of the cancer disease in an untreated individual and should be distinguished from predictive imaging biomarkers and imaging markers of response. A range of tumour characteristics of potential prognostic value can be measured using a variety imaging modalities. However, none has currently been adopted into routine clinical practice. This article considers key examples of emerging prognostic imaging biomarkers and proposes an evaluation framework that aims to demonstrate clinical efficacy and so support their introduction into the clinical arena. With appropriate validation within an established evaluation framework, prognostic imaging biomarkers have the potential to contribute to individualized cancer care, in some cases reducing the financial burden of expensive cancer treatments by facilitating their more rational use. PMID:24060808

Local-Level Prognostics Health Management Systems Framework for Passive AdvSMR Components. Interim Report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ramuhalli, Pradeep; Roy, Surajit; Hirt, Evelyn H.

2014-09-12

This report describes research results to date in support of the integration and demonstration of diagnostics technologies for prototypical AdvSMR passive components (to establish condition indices for monitoring) with model-based prognostics methods. The focus of the PHM methodology and algorithm development in this study is at the localized scale. Multiple localized measurements of material condition (using advanced nondestructive measurement methods), along with available measurements of the stressor environment, enhance the performance of localized diagnostics and prognostics of passive AdvSMR components and systems.

Visit-to-visit blood pressure variability as a prognostic marker in patients with cardiovascular and cerebrovascular diseases--relationships and comparisons with vascular markers of atherosclerosis.

PubMed

Lau, Kui Kai; Wong, Yuen Kwun; Chan, Yap Hang; Teo, Kay Cheong; Chan, Koon Ho; Wai Li, Leonard Sheung; Cheung, Raymond Tak Fai; Siu, Chung Wah; Ho, Shu Leong; Tse, Hung Fat

2014-07-01

Visit-to-visit blood pressure variability (BPV) is a simple surrogate marker for the development of atherosclerotic diseases, cardiovascular and all-cause mortality. Nevertheless, the relative prognostic value of BPV in comparison with other established vascular assessments remain uncertain. We prospectively followed-up 656 high-risk patients with diabetes or established cardiovascular or cerebrovascular diseases for the occurrence of major adverse cardiovascular events (MACEs). Baseline brachial endothelial function, carotid intima-media thickness (IMT) and plaque burden, ankle-brachial index and arterial stiffness were determined. Visit-to-visit BPV were recorded during a mean 18 ± 9 outpatient clinic visits. After a mean 81 ± 12 month's follow-up, 123 patients (19%) developed MACEs. Patients who developed a MACE had significantly higher systolic BPV, more severe endothelial function, arterial stiffness and systemic atherosclerotic burden compared to patients who did not develop a MACE (all P<0.01). BPV significantly correlated with all of the vascular assessments (P<0.01). A high carotid IMT had the greatest prognostic value in predicting development of a MACE (area under receiver operating characteristic curve (AUC) 0.69 ± 0.03, P<0.01). A high BPV also had moderate prognostic value in prediction of MACE (AUC 0.65 ± 0.03, P<0.01). After adjustment of confounding factors, a high BPV remained a significant independent predictor of MACE (hazards ratio 1.67, 95% confidence interval 1.14-2.43, P<0.01). Compared with established surrogate markers of atherosclerosis, visit-to-visit BPV provides similar prognostic information and may represent a new and simple marker for adverse outcomes in patients with vascular diseases. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Localized primary gastrointestinal diffuse large B cell lymphoma received a surgical approach: an analysis of prognostic factors and comparison of staging systems in 101 patients from a single institution.

PubMed

Zhang, Shengting; Wang, Li; Yu, Dong; Shen, Yang; Cheng, Shu; Zhang, Li; Qian, Ying; Shen, Zhixiang; Li, Qinyu; Zhao, Weili

2015-08-15

Diffuse large B cell lymphoma (DLBCL) represents the most common histological subtype of primary gastrointestinal lymphoma and is a heterogeneous group of disease. Prognostic characterization of individual patients is an essential prerequisite for a proper risk-based therapeutic choice. Clinical and pathological prognostic factors were identified, and predictive value of four previously described prognostic systems were assessed in 101 primary gastrointestinal DLBCL (PG-DLBCL) patients with localized disease, including Ann Arbor staging with Musshoff modification, International Prognostic Index (IPI), Lugano classification, and Paris staging system. Univariate factors correlated with inferior survival time were clinical parameters [age>60 years old, multiple extranodal/gastrointestinal involvement, elevated serum lactate dehydrogenase and β2-microglobulin, and decreased serum albumin], as well as pathological parameters (invasion depth beyond serosa, involvement of regional lymph node or adjacent tissue, Ki-67 index, and Bcl-2 expression). Major independent variables of adverse outcome indicated by multivariate analysis were multiple gastrointestinal involvement. In patients unfit for Rituximab but received surgery, radical surgery significantly prolonged the survival time, comparing with alleviative surgery. Addition of Rituximab could overcome the negative prognostic effect of alleviative surgery. Among the four prognostic systems, IPI and Lugano classification clearly separated patients into different risk groups. IPI was able to further stratify the early-stage patients of Lugano classification into groups with distinct prognosis. Radical surgery might be proposed for the patients unfit for Rituximab treatment, and a combination of clinical and pathological staging systems was more helpful to predict the disease outcome of PG-DLBCL patients.

Surgical staging and prognosis in serous borderline ovarian tumours (BOT): A subanalysis of the AGO ROBOT study

PubMed Central

Trillsch, F; Mahner, S; Vettorazzi, E; Woelber, L; Reuss, A; Baumann, K; Keyver-Paik, M-D; Canzler, U; Wollschlaeger, K; Forner, D; Pfisterer, J; Schroeder, W; Muenstedt, K; Richter, B; Fotopoulou, C; Schmalfeldt, B; Burges, A; Ewald-Riegler, N; de Gregorio, N; Hilpert, F; Fehm, T; Meier, W; Hillemanns, P; Hanker, L; Hasenburg, A; Strauss, H-G; Hellriegel, M; Wimberger, P; Kommoss, S; Kommoss, F; Hauptmann, S; du Bois, A

2015-01-01

Background: Incomplete surgical staging is a negative prognostic factor for patients with borderline ovarian tumours (BOT). However, little is known about the prognostic impact of each individual staging procedure. Methods: Clinical parameters of 950 patients with BOT (confirmed by central reference pathology) treated between 1998 and 2008 at 24 German AGO centres were analysed. In 559 patients with serous BOT and adequate ovarian surgery, further recommended staging procedures (omentectomy, peritoneal biopsies, cytology) were evaluated applying Cox regression models with respect to progression-free survival (PFS). Results: For patients with one missing staging procedure, the hazard ratio (HR) for recurrence was 1.25 (95%-CI 0.66–2.39; P=0.497). This risk increased with each additional procedure skipped reaching statistical significance in case of two (HR 1.95; 95%-CI 1.06–3.58; P=0.031) and three missing steps (HR 2.37; 95%-CI 1.22–4.64; P=0.011). The most crucial procedure was omentectomy which retained a statistically significant impact on PFS in multiple analysis (HR 1.91; 95%-CI 1.15–3.19; P=0.013) adjusting for previously established prognostic factors as FIGO stage, tumour residuals, and fertility preservation. Conclusion: Individual surgical staging procedures contribute to the prognosis for patients with serous BOT. In this analysis, recurrence risk increased with each skipped surgical step. This should be considered when re-staging procedures following incomplete primary surgery are discussed. PMID:25562434

Surgical staging and prognosis in serous borderline ovarian tumours (BOT): a subanalysis of the AGO ROBOT study.

PubMed

Trillsch, F; Mahner, S; Vettorazzi, E; Woelber, L; Reuss, A; Baumann, K; Keyver-Paik, M-D; Canzler, U; Wollschlaeger, K; Forner, D; Pfisterer, J; Schroeder, W; Muenstedt, K; Richter, B; Fotopoulou, C; Schmalfeldt, B; Burges, A; Ewald-Riegler, N; de Gregorio, N; Hilpert, F; Fehm, T; Meier, W; Hillemanns, P; Hanker, L; Hasenburg, A; Strauss, H-G; Hellriegel, M; Wimberger, P; Kommoss, S; Kommoss, F; Hauptmann, S; du Bois, A

2015-02-17

Incomplete surgical staging is a negative prognostic factor for patients with borderline ovarian tumours (BOT). However, little is known about the prognostic impact of each individual staging procedure. Clinical parameters of 950 patients with BOT (confirmed by central reference pathology) treated between 1998 and 2008 at 24 German AGO centres were analysed. In 559 patients with serous BOT and adequate ovarian surgery, further recommended staging procedures (omentectomy, peritoneal biopsies, cytology) were evaluated applying Cox regression models with respect to progression-free survival (PFS). For patients with one missing staging procedure, the hazard ratio (HR) for recurrence was 1.25 (95%-CI 0.66-2.39; P=0.497). This risk increased with each additional procedure skipped reaching statistical significance in case of two (HR 1.95; 95%-CI 1.06-3.58; P=0.031) and three missing steps (HR 2.37; 95%-CI 1.22-4.64; P=0.011). The most crucial procedure was omentectomy which retained a statistically significant impact on PFS in multiple analysis (HR 1.91; 95%-CI 1.15-3.19; P=0.013) adjusting for previously established prognostic factors as FIGO stage, tumour residuals, and fertility preservation. Individual surgical staging procedures contribute to the prognosis for patients with serous BOT. In this analysis, recurrence risk increased with each skipped surgical step. This should be considered when re-staging procedures following incomplete primary surgery are discussed.

Evidence-Based Diagnostic Algorithm for Glioma: Analysis of the Results of Pathology Panel Review and Molecular Parameters of EORTC 26951 and 26882 Trials.

PubMed

Kros, Johan M; Huizer, Karin; Hernández-Laín, Aurelio; Marucci, Gianluca; Michotte, Alex; Pollo, Bianca; Rushing, Elisabeth J; Ribalta, Teresa; French, Pim; Jaminé, David; Bekka, Nawal; Lacombe, Denis; van den Bent, Martin J; Gorlia, Thierry

2015-06-10

With the rapid discovery of prognostic and predictive molecular parameters for glioma, the status of histopathology in the diagnostic process should be scrutinized. Our project aimed to construct a diagnostic algorithm for gliomas based on molecular and histologic parameters with independent prognostic values. The pathology slides of 636 patients with gliomas who had been included in EORTC 26951 and 26882 trials were reviewed using virtual microscopy by a panel of six neuropathologists who independently scored 18 histologic features and provided an overall diagnosis. The molecular data for IDH1, 1p/19q loss, EGFR amplification, loss of chromosome 10 and chromosome arm 10q, gain of chromosome 7, and hypermethylation of the promoter of MGMT were available for some of the cases. The slides were divided in discovery (n = 426) and validation sets (n = 210). The diagnostic algorithm resulting from analysis of the discovery set was validated in the latter. In 66% of cases, consensus of overall diagnosis was present. A diagnostic algorithm consisting of two molecular markers and one consensus histologic feature was created by conditional inference tree analysis. The order of prognostic significance was: 1p/19q loss, EGFR amplification, and astrocytic morphology, which resulted in the identification of four diagnostic nodes. Validation of the nodes in the validation set confirmed the prognostic value (P < .001). We succeeded in the creation of a timely diagnostic algorithm for anaplastic glioma based on multivariable analysis of consensus histopathology and molecular parameters. © 2015 by American Society of Clinical Oncology.

Initial FDG-PET/CT predicts survival in adults Ewing sarcoma family of tumors

PubMed Central

Jamet, Bastien; Carlier, Thomas; Campion, Loic; Bompas, Emmanuelle; Girault, Sylvie; Borrely, Fanny; Ferrer, Ludovic; Rousseau, Maxime; Venel, Yann; Kraeber-Bodéré, Françoise; Rousseau, Caroline

2017-01-01

Purpose The aim of this retrospective study was to determine, at baseline, the prognostic value of different FDG-PET/CT quantitative parameters in a homogenous Ewing Sarcoma Family of Tumors (ESFT) adult population, compared with clinically relevant prognostic factors. Methods Adult patients from 3 oncological centers, all with proved ESFT, were retrospectively included. Quantitative FDG-PET/CT parameters (SUV (maximum, peak and mean), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) of the primary lesion of each patient were recorded before treatment, as well as usual clinical prognostic factors (stage of disease, location, tumor size, gender and age). Then, their relation with progression free survival (PFS) and overall survival (OS) was evaluated. Results 32 patients were included. Median age was 21 years (range, 15 to 61). Nineteen patients (59%) were initially metastatic. On multivariate analysis, high SUVmax remained independent predictor of worst OS (p=0.02) and PFS (p=0.019), metastatic disease of worst PFS (p=0.01) and high SUVpeak of worst OS (p=0.01). Optimal prognostic cut-off of SUVpeak was found at 12.5 in multivariate analyses for PFS and OS (p=0.0001). Conclusions FDG-PET/CT, recommended at ESFT diagnosis for initial staging, can be a useful tool for predicting long-term adult patients outcome through semi-quantitative parameters. PMID:29100369

From High-Throughput Microarray-Based Screening to Clinical Application: The Development of a Second Generation Multigene Test for Breast Cancer Prognosis

PubMed Central

Brase, Jan C.; Kronenwett, Ralf; Petry, Christoph; Denkert, Carsten; Schmidt, Marcus

2013-01-01

Several multigene tests have been developed for breast cancer patients to predict the individual risk of recurrence. Most of the first generation tests rely on proliferation-associated genes and are commonly carried out in central reference laboratories. Here, we describe the development of a second generation multigene assay, the EndoPredict test, a prognostic multigene expression test for estrogen receptor (ER) positive, human epidermal growth factor receptor (HER2) negative (ER+/HER2−) breast cancer patients. The EndoPredict gene signature was initially established in a large high-throughput microarray-based screening study. The key steps for biomarker identification are discussed in detail, in comparison to the establishment of other multigene signatures. After biomarker selection, genes and algorithms were transferred to a diagnostic platform (reverse transcription quantitative PCR (RT-qPCR)) to allow for assaying formalin-fixed, paraffin-embedded (FFPE) samples. A comprehensive analytical validation was performed and a prospective proficiency testing study with seven pathological laboratories finally proved that EndoPredict can be reliably used in the decentralized setting. Three independent large clinical validation studies (n = 2,257) demonstrated that EndoPredict offers independent prognostic information beyond current clinicopathological parameters and clinical guidelines. The review article summarizes several important steps that should be considered for the development process of a second generation multigene test and offers a means for transferring a microarray signature from the research laboratory to clinical practice. PMID:27605191

Imaging Tumor Response and Tumoral Heterogeneity in Non-Small Cell Lung Cancer Treated With Antiangiogenic Therapy: Comparison of the Prognostic Ability of RECIST 1.1, an Alternate Method (Crabb), and Image Heterogeneity Analysis.

PubMed

Yip, Connie; Tacelli, Nunzia; Remy-Jardin, Martine; Scherpereel, Arnaud; Cortot, Alexis; Lafitte, Jean-Jacques; Wallyn, Frederic; Remy, Jacques; Bassett, Paul; Siddique, Musib; Cook, Gary J R; Landau, David B; Goh, Vicky

2015-09-01

We aimed to assess computed tomography (CT) intratumoral heterogeneity changes, and compared the prognostic ability of the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, an alternate response method (Crabb), and CT heterogeneity in non-small cell lung cancer treated with chemotherapy with and without bevacizumab. Forty patients treated with chemotherapy (group C) or chemotherapy and bevacizumab (group BC) underwent contrast-enhanced CT at baseline and after 1, 3, and 6 cycles of chemotherapy. Radiologic response was assessed using RECIST 1.1 and an alternate method. CT heterogeneity analysis generating global and locoregional parameters depicting tumor image spatial intensity characteristics was performed. Heterogeneity parameters between the 2 groups were compared using the Mann-Whitney U test. Associations between heterogeneity parameters and radiologic response with overall survival were assessed using Cox regression. Global and locoregional heterogeneity parameters changed with treatment, with increased tumor heterogeneity in group BC. Entropy [group C: median -0.2% (interquartile range -2.2, 1.7) vs. group BC: 0.7% (-0.7, 3.5), P=0.10] and busyness [-27.7% (-62.2, -5.0) vs. -11.5% (-29.1, 92.4), P=0.10] showed a greater reduction in group C, whereas uniformity [1.9% (-8.0, 9.8) vs. -5.0% (-13.9, 5.6), P=0.10] showed a relative increase after 1 cycle but did not reach statistical significance. Two (9%) and 1 (6%) additional responders were identified using the alternate method compared with RECIST in group C and group BC, respectively. Heterogeneity parameters were not significant prognostic factors. The alternate response method described by Crabb identified more responders compared with RECIST. However, both criteria and baseline imaging heterogeneity parameters were not prognostic of survival.

[Prognostic parameters in liver cirrhosis, varicose bleeding and sclerosing therapy. Prospective comparison of a prognostic system with the Child classification obtained by discriminant analysis].

PubMed

Sauerbruch, T; Ansari, H; Wotzka, R; Soehendra, N; Köpcke, W

1988-01-08

Prospective prognosis systems for predicting half-year death-rate after bleeding from oesophageal varices and sclerotherapy were tested on 129 patients. The receiver-operating-characteristic curves of three discriminant scores were compared with the Child-Pugh classification. It was found that the latter is still the best for prognosticating the course of the disease. A simplified discriminant score which contains as its only factors bilirubin and the Quick value does, however, give nearly as good information.

Immunological metagene signatures derived from immunogenic cancer cell death associate with improved survival of patients with lung, breast or ovarian malignancies: A large-scale meta-analysis

PubMed Central

Garg, Abhishek D.; De Ruysscher, Dirk; Agostinis, Patrizia

2016-01-01

ABSTRACT The emerging role of the cancer cell-immune cell interface in shaping tumorigenesis/anticancer immunotherapy has increased the need to identify prognostic biomarkers. Henceforth, our primary aim was to identify the immunogenic cell death (ICD)-derived metagene signatures in breast, lung and ovarian cancer that associate with improved patient survival. To this end, we analyzed the prognostic impact of differential gene-expression of 33 pre-clinically-validated ICD-parameters through a large-scale meta-analysis involving 3,983 patients (‘discovery’ dataset) across lung (1,432), breast (1,115) and ovarian (1,436) malignancies. The main results were also substantiated in ‘validation’ datasets consisting of 818 patients of same cancer-types (i.e. 285 breast/274 lung/259 ovarian). The ICD-associated parameters exhibited a highly-clustered and largely cancer type-specific prognostic impact. Interestingly, we delineated ICD-derived consensus-metagene signatures that exhibited a positive prognostic impact that was either cancer type-independent or specific. Importantly, most of these ICD-derived consensus-metagenes (acted as attractor-metagenes and thereby) ‘attracted’ highly co-expressing sets of genes or convergent-metagenes. These convergent-metagenes also exhibited positive prognostic impact in respective cancer types. Remarkably, we found that the cancer type-independent consensus-metagene acted as an ‘attractor’ for cancer-specific convergent-metagenes. This reaffirms that the immunological prognostic landscape of cancer tends to segregate between cancer-independent and cancer-type specific gene signatures. Moreover, this prognostic landscape was largely dominated by the classical T cell activity/infiltration/function-related biomarkers. Interestingly, each cancer type tended to associate with biomarkers representing a specific T cell activity or function rather than pan-T cell biomarkers. Thus, our analysis confirms that ICD can serve as a platform for discovery of novel prognostic metagenes. PMID:27057433

Gender and age related predictive value of walk test in heart failure: do anthropometrics matter in clinical practice?

PubMed

Frankenstein, L; Remppis, A; Graham, J; Schellberg, D; Sigg, C; Nelles, M; Katus, H A; Zugck, C

2008-07-21

The six-minute walk test (6 WT) is a valid and reliable predictor of morbidity and mortality in chronic heart failure (CHF) patients, frequently used as an endpoint or target in clinical trials. As opposed to spiroergometry, improvement of its prognostic accuracy by correction for height, weight, age and gender has not yet been attempted comprehensively despite known influences of these parameters. We recorded the 6 WT of 1035 CHF patients, attending clinic from 1995 to 2005. The 1-year prognostic value of 6 WT was calculated, alone and after correction for height, weight, BMI and/or age. Analysis was performed on the entire cohort, on males and females separately and stratified according to BMI (<25, 25-30 and >30 kg/m(2)). 6 WT weakly correlated with age (r=-0.32; p<0.0001), height (r=0.2; p<0.0001), weight (r=0.11; p<0.001), not with BMI (r=0.01; p=ns). The 6 WT was a strong predictor of 1-year mortality in both genders, both as a single and age corrected parameter. Parameters derived from correction of 6 WT for height, weight or BMI did not improve the prognostic value in univariate analysis for either gender. Comparison of the receiver operated characteristics showed no significant gain in prognostic accuracy from any derived variable, either for males or females. The six-minute walk test is a valid tool for risk prediction in both male and female CHF patients. In both genders, correcting 6 WT distance for height, weight or BMI alone, or adjusting for age, does not increase the prognostic power of this tool.

SENIORLAB: a prospective observational study investigating laboratory parameters and their reference intervals in the elderly.

PubMed

Risch, Martin; Nydegger, Urs; Risch, Lorenz

2017-01-01

In clinical practice, laboratory results are often important for making diagnostic, therapeutic, and prognostic decisions. Interpreting individual results relies on accurate reference intervals and decision limits. Despite the considerable amount of resources in clinical medicine spent on elderly patients, accurate reference intervals for the elderly are rarely available. The SENIORLAB study set out to determine reference intervals in the elderly by investigating a large variety of laboratory parameters in clinical chemistry, hematology, and immunology. The SENIORLAB study is an observational, prospective cohort study. Subjectively healthy residents of Switzerland aged 60 years and older were included for baseline examination (n = 1467), where anthropometric measurements were taken, medical history was reviewed, and a fasting blood sample was drawn under optimal preanalytical conditions. More than 110 laboratory parameters were measured, and a biobank was set up. The study participants are followed up every 3 to 5 years for quality of life, morbidity, and mortality. The primary aim is to evaluate different laboratory parameters at age-related reference intervals. The secondary aims of this study include the following: identify associations between different parameters, identify diagnostic characteristics to diagnose different circumstances, identify the prevalence of occult disease in subjectively healthy individuals, and identify the prognostic factors for the investigated outcomes, including mortality. To obtain better grounds to justify clinical decisions, specific reference intervals for laboratory parameters of the elderly are needed. Reference intervals are obtained from healthy individuals. A major obstacle when obtaining reference intervals in the elderly is the definition of health in seniors because individuals without any medical condition and any medication are rare in older adulthood. Reference intervals obtained from such individuals cannot be considered representative for seniors in a status of age-specific normal health. In addition to the established methods for determining reference intervals, this longitudinal study utilizes a unique approach, in that survival and long-term well-being are taken as indicators of health in seniors. This approach is expected to provide robust and representative reference intervals that are obtained from an adequate reference population and not a collective of highly selected individuals. The present study was registered under International Standard Randomized Controlled Trial Number registry: ISRCTN53778569.

A New Prognostic Staging System for Rectal Cancer

PubMed Central

Ueno, Hideki; Price, Ashley B.; Wilkinson, Kay H.; Jass, Jeremy R.; Mochizuki, Hidetaka; Talbot, Ian C.

2004-01-01

Objective: To clarify the appropriateness of tumor “budding,” a quantifiable histologic variable, as 1 parameter in the construction of a new prognostic grading system for rectal cancer. Summary Background Data: Patient division according to an accurate prognostic prediction could enhance the effectiveness of postoperative adjuvant therapy and follow-up. Patients and Methods: Tumor budding was defined as an isolated cancer cell or a cluster composed of fewer than 5 cells in the invasive frontal region, and was divided into 2 grades based on its number within a microscopic field of ×250. We analyzed 2 discrete cohorts comprising 638 and 476 patients undergoing potentially curative surgery. Results: In the first cohort, high-grade budding (10 or more foci in a field) was observed in 30% of patients and was significantly associated with a lower 5-year survival rate (41%) than low-grade budding (84%). Similarly, in the second cohort, the 5-year survival rate was 43% in high-grade budding patients and 83% in low-grade budding patients. In both cohorts, multivariate analyses verified budding to be an independent prognosticator, together with nodal involvement and extramural spread. These 3 variables were given weighted scores, and the score range was divided to provide 5 prognostic groups (97%; 86%; 61%; 39%; 17% 5-year survival). The model was tested on the second cohort, and similar prognostic results were obtained. Conclusions: We propose that because of its relevance to prognosis and its reproducibility, budding is an excellent parameter for use in a grading system to provide a confident prediction of clinical outcome. PMID:15492565

A critical prognostic analysis of neutrophil-lymphocyte ratio for patients undergoing nephroureterectomy due to upper urinary tract urothelial carcinoma.

PubMed

Altan, Mesut; Haberal, Hakan Bahadır; Akdoğan, Bülent; Özen, Haluk

2017-10-01

To determine preoperative serum complete blood count parameters that affects survival of patients who underwent surgery for upper urinary tract urothelial cancer (UUT-UC). Since 1990, 150 patients underwent nephroureterectomy with bladder cuff excision for UUT-UC at Hacettepe University. Patients with a history of muscle-invasive bladder cancer, adjuvant chemotherapy or metastasis at the time of diagnosis were excluded. One hundred and thirteen patients without infective symptoms and with a full set of serum data were evaluated retrospectively. Effects of the neutrophil-lymphocyte ratio (NLR), lymphocyte-monocyte ratio (LMR), platelet-lymphocyte ratio (PLR), and leukocyte count on disease-free survival (DFS) and progression-free survival (PFS) were investigated. Threshold values for each parameter to predict PFS were calculated. The mean age and median follow-up were 63.7 ± 11.1 years and 34 (3-186) months, respectively. Male to female ratio was 86/27. The 5-years PFS (bladder recurrence was excluded) and DFS were 59.6 and 38.4%, respectively. In multivariate analysis, NLR was independent prognostic factor for PFS and DFS (p = 0.006 and p = 0.021, respectively) while LMR was prognostic only for PFS (p = 0.037). For UUT-UC, NLR is a prognostic factor for PFS and DFS, while LMR is a prognostic indicator for PFS in present series.

New breast cancer prognostic factors identified by computer-aided image analysis of HE stained histopathology images

PubMed Central

Chen, Jia-Mei; Qu, Ai-Ping; Wang, Lin-Wei; Yuan, Jing-Ping; Yang, Fang; Xiang, Qing-Ming; Maskey, Ninu; Yang, Gui-Fang; Liu, Juan; Li, Yan

2015-01-01

Computer-aided image analysis (CAI) can help objectively quantify morphologic features of hematoxylin-eosin (HE) histopathology images and provide potentially useful prognostic information on breast cancer. We performed a CAI workflow on 1,150 HE images from 230 patients with invasive ductal carcinoma (IDC) of the breast. We used a pixel-wise support vector machine classifier for tumor nests (TNs)-stroma segmentation, and a marker-controlled watershed algorithm for nuclei segmentation. 730 morphologic parameters were extracted after segmentation, and 12 parameters identified by Kaplan-Meier analysis were significantly associated with 8-year disease free survival (P < 0.05 for all). Moreover, four image features including TNs feature (HR 1.327, 95%CI [1.001 - 1.759], P = 0.049), TNs cell nuclei feature (HR 0.729, 95%CI [0.537 - 0.989], P = 0.042), TNs cell density (HR 1.625, 95%CI [1.177 - 2.244], P = 0.003), and stromal cell structure feature (HR 1.596, 95%CI [1.142 - 2.229], P = 0.006) were identified by multivariate Cox proportional hazards model to be new independent prognostic factors. The results indicated that CAI can assist the pathologist in extracting prognostic information from HE histopathology images for IDC. The TNs feature, TNs cell nuclei feature, TNs cell density, and stromal cell structure feature could be new prognostic factors. PMID:26022540

Prognostic value of S100/CD31 and S100/podoplanin double immunostaining in mucosal malignant melanoma of the head and neck.

PubMed

Wermker, Kai; Brauckmann, Till; Klein, Martin; Haßfeld, Stefan; Schulze, Hans-Joachim; Hallermann, Christian

2015-09-01

In uncommon mucosal melanomas of the head and neck established prognostic factors are rare and controversially discussed. The purpose of this study was to evaluate outcome and value of S100/podoplanin and S100/CD31 double immunostaining in head and neck mucosal melanomas. Retrospectively, patients with head and neck mucosal melanomas treated between 1973 and 2008 were analyzed. S100/podoplanin and S100/CD31 immunostaining were performed to detect lymph vessel invasion (LVI) and blood vessel invasion (BVI). Predictive parameters for disease-specific survival (DSS) were identified using univariate and multivariate statistics. Forty-two patients with head and neck mucosal melanoma were included. Three-year, 5-year, and 10-year DSS rates were 59%, 44%, and 20%, respectively. Age above 70 years, occurrence of distant metastasis, LVI, and BVI were significantly associated with shorter DSS time (p < .05), whereas localization at the conjunctiva showed better outcome. S100/podoplanin and S100/CD31 double immunostaining detect reliable LVI and BVI in head and neck mucosal melanoma and both are associated significantly with worse prognosis. © 2014 Wiley Periodicals, Inc.

Clinicopathological relevance of tumour grading in canine osteosarcoma.

PubMed

Loukopoulos, P; Robinson, W F

2007-01-01

Tumour grading assesses biological aggressiveness and is of prognostic significance in many malignancies. The clinicopathological features of 140 primary canine osteosarcomas and their metastases were analysed, and the interrelations between them and an established grading system and its constituent parameters (mitotic index, necrosis, pleomorphism) were examined. Of these tumours, 35% were grade III (high-grade), 37% grade II and 28% grade I. Primary tumours that had metastasized were of significantly higher grade than non-metastatic osteosarcomas. Osteosarcomas belonging to the osteoblastic minimally productive subtype, but not chondroblastic or telangiectatic subtypes, differed from fibroblastic osteosarcomas in being associated with a significantly higher number of high-grade cases. Dogs younger than 4 years of age had osteosarcomas with higher grade, score and mitotic index than did older animals. Appendicular differed from axial tumours in having a higher mitotic index; distal differed from proximal tumours in being of higher grade; cranial tumours differed from tumours in most other sites in being of lower grade and lower mitotic index. Rib osteosarcomas showed a particularly high degree of necrosis. The mitotic index varied widely between tumour locations. Pleomorphism did not have prognostic merit when examined separately, as most osteosarcomas were highly pleomorphic.

Dynamic Contrast-Enhanced MRI of Cervical Cancers: Temporal Percentile Screening of Contrast Enhancement Identifies Parameters for Prediction of Chemoradioresistance

DOE Office of Scientific and Technical Information (OSTI.GOV)

Andersen, Erlend K.F.; Hole, Knut Hakon; Lund, Kjersti V.

Purpose: To systematically screen the tumor contrast enhancement of locally advanced cervical cancers to assess the prognostic value of two descriptive parameters derived from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Methods and Materials: This study included a prospectively collected cohort of 81 patients who underwent DCE-MRI with gadopentetate dimeglumine before chemoradiotherapy. The following descriptive DCE-MRI parameters were extracted voxel by voxel and presented as histograms for each time point in the dynamic series: normalized relative signal increase (nRSI) and normalized area under the curve (nAUC). The first to 100th percentiles of the histograms were included in a log-rank survival test,more » resulting in p value and relative risk maps of all percentile-time intervals for each DCE-MRI parameter. The maps were used to evaluate the robustness of the individual percentile-time pairs and to construct prognostic parameters. Clinical endpoints were locoregional control and progression-free survival. The study was approved by the institutional ethics committee. Results: The p value maps of nRSI and nAUC showed a large continuous region of percentile-time pairs that were significantly associated with locoregional control (p < 0.05). These parameters had prognostic impact independent of tumor stage, volume, and lymph node status on multivariate analysis. Only a small percentile-time interval of nRSI was associated with progression-free survival. Conclusions: The percentile-time screening identified DCE-MRI parameters that predict long-term locoregional control after chemoradiotherapy of cervical cancer.« less

Prognostic usefulness of derived T2-weighted fetal magnetic resonance imaging measurements in congenital diaphragmatic hernia.

PubMed

Sebastià, C; Gomez, O; Salvador, R; Buñesch, L; Garcia, R; Nicolau, C

2015-01-01

To determine the usefulness of various parameters based on T2-weighted fetal magnetic resonance (MR) imaging measurements of the uninvolved lung for the neonatal prognosis of congenital diaphragmatic hernia (CDH). We used ultrasonography and MR imaging to study 28 fetuses with CDH. We retrospectively analyzed a) on fetal ultrasonography, the observed-to-expected lung to head ratio (O/E LHR) and the position of the liver, and b) on fetal MR imaging, the lung-liver signal ratio (LLSR) and the lungcerebrospinal fluid ratio (L/CSF SR). To determine the prognostic value of these parameters, we compared them with the following postnatal parameters: survival, pulmonary hypertension, need for oxygen supplementation, and need for extracorporeal membrane oxygenation. We found significant differences between O/E LHR and the need for postnatal extracorporeal membrane oxygenation (P=.033) and postnatal survival (P=.01). We also found significant differences in LLSR between fetuses that survived more than 45 days and those that died within 45 days (1.91 vs. 2.56; P=.039). In fetuses with CDH, the LLSR correlates with postnatal survival and can potentially be used as a prognostic parameter in CDH. Copyright © 2013 SERAM. Published by Elsevier España, S.L.U. All rights reserved.

Liver maximum capacity (LiMAx) test as a helpful prognostic tool in acute liver failure with sepsis: a case report.

PubMed

Buechter, Matthias; Gerken, Guido; Hoyer, Dieter P; Bertram, Stefanie; Theysohn, Jens M; Thodou, Viktoria; Kahraman, Alisan

2018-06-20

Acute liver failure (ALF) is a life-threatening entity particularly when infectious complications worsen the clinical course. Urgent liver transplantation (LT) is frequently the only curative treatment. However, in some cases, recovery is observed under conservative treatment. Therefore, prognostic tools for estimating course of the disease are of great clinical interest. Since laboratory parameters sometimes lack sensitivity and specificity, enzymatic liver function measured by liver maximum capacity (LiMAx) test may offer novel and valuable additional information in this setting. We here report the case of a formerly healthy 20-year old male caucasian patient who was admitted to our clinic for ALF of unknown origin in December 2017. Laboratory parameters confirmed the diagnosis with an initial MELD score of 28 points. Likewise, enzymatic liver function was significantly impaired with a value of 147 [> 315] μg/h/kg. Clinical and biochemical analyses for viral-, autoimmune-, or drug-induced hepatitis were negative. Liver synthesis parameters further deteriorated reaching a MELD score of 40 points whilst clinical course was complicated by septic pneumonia leading to severe hepatic encephalopathy grade III-IV, finally resulting in mechanical ventilation of the patient. Interestingly, although clinical course and laboratory data suggested poor outcome, serial LiMAx test revealed improvement of the enzymatic liver function at this time point increasing to 169 μg/h/kg. Clinical condition and laboratory data slowly improved likewise, however with significant time delay of 11 days. Finally, the patient could be dismissed from our clinic after 37 days. Estimating prognosis in patients with ALF is challenging by use of the established scores. In our case, improvement of enzymatic liver function measured by the LiMAx test was the first parameter predicting beneficial outcome in a patient with ALF complicated by sepsis.

Water-Exchange-Modified Kinetic Parameters from Dynamic Contrast-Enhanced MRI as Prognostic Biomarkers of Survival in Advanced Hepatocellular Carcinoma Treated with Antiangiogenic Monotherapy

PubMed Central

Lee, Sang Ho; Hayano, Koichi; Zhu, Andrew X.; Sahani, Dushyant V.; Yoshida, Hiroyuki

2015-01-01

Background To find prognostic biomarkers in pretreatment dynamic contrast-enhanced MRI (DCE-MRI) water-exchange-modified (WX) kinetic parameters for advanced hepatocellular carcinoma (HCC) treated with antiangiogenic monotherapy. Methods Twenty patients with advanced HCC underwent DCE-MRI and were subsequently treated with sunitinib. Pretreatment DCE-MRI data on advanced HCC were analyzed using five different WX kinetic models: the Tofts-Kety (WX-TK), extended TK (WX-ETK), two compartment exchange, adiabatic approximation to tissue homogeneity (WX-AATH), and distributed parameter (WX-DP) models. The total hepatic blood flow, arterial flow fraction (γ), arterial blood flow (BF A), portal blood flow, blood volume, mean transit time, permeability-surface area product, fractional interstitial volume (v I), extraction fraction, mean intracellular water molecule lifetime (τ C), and fractional intracellular volume (v C) were calculated. After receiver operating characteristic analysis with leave-one-out cross-validation, individual parameters for each model were assessed in terms of 1-year-survival (1YS) discrimination using Kaplan-Meier analysis, and association with overall survival (OS) using univariate Cox regression analysis with permutation testing. Results The WX-TK-model-derived γ (P = 0.022) and v I (P = 0.010), and WX-ETK-model-derived τ C (P = 0.023) and v C (P = 0.042) were statistically significant prognostic biomarkers for 1YS. Increase in the WX-DP-model-derived BF A (P = 0.025) and decrease in the WX-TK, WX-ETK, WX-AATH, and WX-DP-model-derived v C (P = 0.034, P = 0.038, P = 0.028, P = 0.041, respectively) were significantly associated with an increase in OS. Conclusions The WX-ETK-model-derived v C was an effective prognostic biomarker for advanced HCC treated with sunitinib. PMID:26366997

Nonlinear-drifted Brownian motion with multiple hidden states for remaining useful life prediction of rechargeable batteries

NASA Astrophysics Data System (ADS)

Wang, Dong; Zhao, Yang; Yang, Fangfang; Tsui, Kwok-Leung

2017-09-01

Brownian motion with adaptive drift has attracted much attention in prognostics because its first hitting time is highly relevant to remaining useful life prediction and it follows the inverse Gaussian distribution. Besides linear degradation modeling, nonlinear-drifted Brownian motion has been developed to model nonlinear degradation. Moreover, the first hitting time distribution of the nonlinear-drifted Brownian motion has been approximated by time-space transformation. In the previous studies, the drift coefficient is the only hidden state used in state space modeling of the nonlinear-drifted Brownian motion. Besides the drift coefficient, parameters of a nonlinear function used in the nonlinear-drifted Brownian motion should be treated as additional hidden states of state space modeling to make the nonlinear-drifted Brownian motion more flexible. In this paper, a prognostic method based on nonlinear-drifted Brownian motion with multiple hidden states is proposed and then it is applied to predict remaining useful life of rechargeable batteries. 26 sets of rechargeable battery degradation samples are analyzed to validate the effectiveness of the proposed prognostic method. Moreover, some comparisons with a standard particle filter based prognostic method, a spherical cubature particle filter based prognostic method and two classic Bayesian prognostic methods are conducted to highlight the superiority of the proposed prognostic method. Results show that the proposed prognostic method has lower average prediction errors than the particle filter based prognostic methods and the classic Bayesian prognostic methods for battery remaining useful life prediction.

Evaluation of an inflammation-based prognostic score in patients with metastatic renal cancer.

PubMed

Ramsey, Sara; Lamb, Gavin W A; Aitchison, Michael; Graham, John; McMillan, Donald C

2007-01-15

Recently, it was shown that an inflammation-based prognostic score, the Glasgow Prognostic Score (GPS), provides additional prognostic information in patients with advanced cancer. The objective of the current study was to examine the value of the GPS compared with established scoring systems in predicting cancer-specific survival in patients with metastatic renal cancer. One hundred nineteen patients who underwent immunotherapy for metastatic renal cancer were recruited. The Memorial Sloan-Kettering Cancer Center (MSKCC) score and the Metastatic Renal Carcinoma Comprehensive Prognostic System (MRCCPS) score were calculated as described previously. Patients who had both an elevated C-reactive protein level (>10 mg/L) and hypoalbuminemia (<35 g/L) were allocated a GPS of 2. Patients who had only 1 of those 2 biochemical abnormalities were allocated a GPS of 1. Patients who had neither abnormality were allocated a GPS of 0. On multivariate analysis of significant individual factors, only calcium (hazard ratio [HR], 3.21; 95% confidence interval [95% CI], 1.51-6.83; P = .002), white cell count (HR, 1.66; 95% CI, 1.17-2.35; P = .004), albumin (HR, 2.63; 95% CI, 1.38-5.03; P = .003), and C-reactive protein (HR, 2.85; 95% CI; 1.49-5.45; P = .002) were associated independently with cancer-specific survival. On multivariate analysis of the different scoring systems, the MSKCC (HR, 1.88; 95% CI, 1.22-2.88; P = .004), the MRCCPS (HR, 1.42; 95% CI, 0.97-2.09; P = .071), and the GPS (HR, 2.35; 95% CI, 1.51-3.67; P < .001) were associated independently with cancer-specific survival. An inflammation-based prognostic score (GPS) predicted survival independent of established scoring systems in patients with metastatic renal cancer.

Prediction of overall survival for metastatic pancreatic cancer: Development and validation of a prognostic nomogram with data from open clinical trial and real-world study.

PubMed

Hang, Junjie; Wu, Lixia; Zhu, Lina; Sun, Zhiqiang; Wang, Ge; Pan, Jingjing; Zheng, Suhua; Xu, Kequn; Du, Jiadi; Jiang, Hua

2018-06-01

It is necessary to develop prognostic tools of metastatic pancreatic cancer (MPC) for optimizing therapeutic strategies. Thus, we tried to develop and validate a prognostic nomogram of MPC. Data from 3 clinical trials (NCT00844649, NCT01124786, and NCT00574275) and 133 Chinese MPC patients were used for analysis. The former 2 trials were taken as the training cohort while NCT00574275 was used as the validation cohort. In addition, 133 MPC patients treated in China were taken as the testing cohort. Cox regression model was used to investigate prognostic factors in the training cohort. With these factors, we established a nomogram and verified it by Harrell's concordance index (C-index) and calibration plots. Furthermore, the nomogram was externally validated in the validation cohort and testing cohort. In the training cohort (n = 445), performance status, liver metastasis, Carbohydrate antigen 19-9 (CA19-9) log-value, absolute neutrophil count (ANC), and albumin were independent prognostic factors for overall survival (OS). A nomogram was established with these factors to predict OS and survival probabilities. The nomogram showed an acceptable discrimination ability (C-index: .683) and good calibration, and was further externally validated in the validation cohort (n = 273, C-index: .699) and testing cohort (n = 133, C-index: .653).The nomogram total points (NTP) had the potential to stratify patients into 3-risk groups with median OS of 11.7, 7.0 and 3.7 months (P < .001), respectively. In conclusion, the prognostic nomogram with NTP can predict OS for patients with MPC with considerable accuracy. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Prognostic Modeling in Pathologic N1 Breast Cancer Without Elective Nodal Irradiation After Current Standard Systemic Management.

PubMed

Yu, Jeong Il; Park, Won; Choi, Doo Ho; Huh, Seung Jae; Nam, Seok Jin; Kim, Seok Won; Lee, Jeong Eon; Kil, Won Ho; Im, Young-Hyuck; Ahn, Jin Seok; Park, Yeon Hee; Cho, Eun Yoon

2015-08-01

This study was conducted to establish a prognostic model in patients with pathologic N1 (pN1) breast cancer who have not undergone elective nodal irradiation (ENI) under the current standard management and to suggest possible indications for ENI. We performed a retrospective study with patients with pN1 breast cancer who received the standard local and preferred adjuvant chemotherapy treatment without neoadjuvant chemotherapy and ENI from January 2005 to June 2011. Most of the indicated patients received endocrine and trastuzumab therapy. In 735 enrolled patients, the median follow-up period was 58.4 months (range, 7.2-111.3 months). Overall, 55 recurrences (7.4%) developed, and locoregional recurrence was present in 27 patients (3.8%). Recurrence-free survival was significantly related to lymphovascular invasion (P = .04, hazard ratio [HR], 1.83; 95% confidence interval [CI], 1.03-2.88), histologic grade (P = .03, HR, 2.57; 95% CI, 1.05-6.26), and nonluminal A subtype (P = .02, HR, 3.04; 95% CI, 1.23-7.49) in multivariate analysis. The prognostic model was established by these 3 prognostic factors. Recurrence-free survival was less than 90% at 5 years in cases with 2 or 3 factors. The prognostic model has stratified risk groups in pN1 breast cancer without ENI. Patients with 2 or more factors should be considered for ENI. Copyright © 2015 Elsevier Inc. All rights reserved.

Development and Validation of a Lifecycle-based Prognostics Architecture with Test Bed Validation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hines, J. Wesley; Upadhyaya, Belle; Sharp, Michael

On-line monitoring and tracking of nuclear plant system and component degradation is being investigated as a method for improving the safety, reliability, and maintainability of aging nuclear power plants. Accurate prediction of the current degradation state of system components and structures is important for accurate estimates of their remaining useful life (RUL). The correct quantification and propagation of both the measurement uncertainty and model uncertainty is necessary for quantifying the uncertainty of the RUL prediction. This research project developed and validated methods to perform RUL estimation throughout the lifecycle of plant components. Prognostic methods should seamlessly operate from beginning ofmore » component life (BOL) to end of component life (EOL). We term this "Lifecycle Prognostics." When a component is put into use, the only information available may be past failure times of similar components used in similar conditions, and the predicted failure distribution can be estimated with reliability methods such as Weibull Analysis (Type I Prognostics). As the component operates, it begins to degrade and consume its available life. This life consumption may be a function of system stresses, and the failure distribution should be updated to account for the system operational stress levels (Type II Prognostics). When degradation becomes apparent, this information can be used to again improve the RUL estimate (Type III Prognostics). This research focused on developing prognostics algorithms for the three types of prognostics, developing uncertainty quantification methods for each of the algorithms, and, most importantly, developing a framework using Bayesian methods to transition between prognostic model types and update failure distribution estimates as new information becomes available. The developed methods were then validated on a range of accelerated degradation test beds. The ultimate goal of prognostics is to provide an accurate assessment for RUL predictions, with as little uncertainty as possible. From a reliability and maintenance standpoint, there would be improved safety by avoiding all failures. Calculated risk would decrease, saving money by avoiding unnecessary maintenance. One major bottleneck for data-driven prognostics is the availability of run-to-failure degradation data. Without enough degradation data leading to failure, prognostic models can yield RUL distributions with large uncertainty or mathematically unsound predictions. To address these issues a "Lifecycle Prognostics" method was developed to create RUL distributions from Beginning of Life (BOL) to End of Life (EOL). This employs established Type I, II, and III prognostic methods, and Bayesian transitioning between each Type. Bayesian methods, as opposed to classical frequency statistics, show how an expected value, a priori, changes with new data to form a posterior distribution. For example, when you purchase a component you have a prior belief, or estimation, of how long it will operate before failing. As you operate it, you may collect information related to its condition that will allow you to update your estimated failure time. Bayesian methods are best used when limited data are available. The use of a prior also means that information is conserved when new data are available. The weightings of the prior belief and information contained in the sampled data are dependent on the variance (uncertainty) of the prior, the variance (uncertainty) of the data, and the amount of measured data (number of samples). If the variance of the prior is small compared to the uncertainty of the data, the prior will be weighed more heavily. However, as more data are collected, the data will be weighted more heavily and will eventually swamp out the prior in calculating the posterior distribution of model parameters. Fundamentally Bayesian analysis updates a prior belief with new data to get a posterior belief. The general approach to applying the Bayesian method to lifecycle prognostics consisted of identifying the prior, which is the RUL estimate and uncertainty from the previous prognostics type, and combining it with observational data related to the newer prognostics type. The resulting lifecycle prognostics algorithm uses all available information throughout the component lifecycle.« less

Zone-size nonuniformity of 18F-FDG PET regional textural features predicts survival in patients with oropharyngeal cancer.

PubMed

Cheng, Nai-Ming; Fang, Yu-Hua Dean; Lee, Li-yu; Chang, Joseph Tung-Chieh; Tsan, Din-Li; Ng, Shu-Hang; Wang, Hung-Ming; Liao, Chun-Ta; Yang, Lan-Yan; Hsu, Ching-Han; Yen, Tzu-Chen

2015-03-01

The question as to whether the regional textural features extracted from PET images predict prognosis in oropharyngeal squamous cell carcinoma (OPSCC) remains open. In this study, we investigated the prognostic impact of regional heterogeneity in patients with T3/T4 OPSCC. We retrospectively reviewed the records of 88 patients with T3 or T4 OPSCC who had completed primary therapy. Progression-free survival (PFS) and disease-specific survival (DSS) were the main outcome measures. In an exploratory analysis, a standardized uptake value of 2.5 (SUV 2.5) was taken as the cut-off value for the detection of tumour boundaries. A fixed threshold at 42 % of the maximum SUV (SUVmax 42 %) and an adaptive threshold method were then used for validation. Regional textural features were extracted from pretreatment (18)F-FDG PET/CT images using the grey-level run length encoding method and grey-level size zone matrix. The prognostic significance of PET textural features was examined using receiver operating characteristic (ROC) curves and Cox regression analysis. Zone-size nonuniformity (ZSNU) was identified as an independent predictor of PFS and DSS. Its prognostic impact was confirmed using both the SUVmax 42 % and the adaptive threshold segmentation methods. Based on (1) total lesion glycolysis, (2) uniformity (a local scale texture parameter), and (3) ZSNU, we devised a prognostic stratification system that allowed the identification of four distinct risk groups. The model combining the three prognostic parameters showed a higher predictive value than each variable alone. ZSNU is an independent predictor of outcome in patients with advanced T-stage OPSCC, and may improve their prognostic stratification.

Glasgow Prognostic Score is a predictor of perioperative and long-term outcome in patients with only surgically treated esophageal cancer.

PubMed

Vashist, Yogesh K; Loos, Julian; Dedow, Josephine; Tachezy, Michael; Uzunoglu, Guentac; Kutup, Asad; Yekebas, Emre F; Izbicki, Jakob R

2011-04-01

Systemic inflammation (SI) plays a pivotal role in cancer. C-reactive protein (CRP) and albumin as parameters of SI form the Glasgow Prognostic Score (GPS). The purpose of the study was to evaluate the potential prognostic role of GPS in a homogeneous population of esophageal cancer (EC) patients undergoing only resection. GPS was evaluated on the basis of admission blood sample taken before surgery. Patients with a CRP < 10 mg/L and albumin > 35 g/L were allocated to GPS0 group. If only CRP was increased or albumin decreased patients were allocated to the GPS1 and patients in whom CRP was ≥10 mg/L and albumin level ≤35 g/L were classified as GPS2. GPS was correlated to clinicopathological parameters and clinical outcome. Increasing GPS significantly correlated with more aggressive tumor biology in terms of tumor size (P < 0.001), presence of regional (P = 0.01) and nonregional lymph node metastasis (P = 0.02), and higher tumor recurrence rate (P < 0.001). Furthermore, GPS was identified as an independent prognosticator of perioperative morbidity (odds ratio 1.9; P = 0.03). In addition, a gradual decrease in disease-free and overall survival was evident between the three GPS subgroups. Survival differences between the GPS groups remained apparent even after stratification of the study population to underlying tumor type and nodal status. GPS was identified as a strong prognosticator of tumor recurrence (hazard ratio 2.5; P < 0.001) and survival (hazard ratio 3.0; P < 0.001) in EC. GPS represents a strong prognosticator of perioperative morbidity and long-term outcome in resected EC patients without neoadjuvant or adjuvant treatment.

Diagnostic and Prognostic Value of Long-Axis Strain and Myocardial Contraction Fraction Using Standard Cardiovascular MR Imaging in Patients with Nonischemic Dilated Cardiomyopathies.

PubMed

Arenja, Nisha; Riffel, Johannes H; Fritz, Thomas; André, Florian; Aus dem Siepen, Fabian; Mueller-Hennessen, Matthias; Giannitsis, Evangelos; Katus, Hugo A; Friedrich, Matthias G; Buss, Sebastian J

2017-06-01

Purpose To assess the utility of established functional markers versus two additional functional markers derived from standard cardiovascular magnetic resonance (MR) images for their incremental diagnostic and prognostic information in patients with nonischemic dilated cardiomyopathy (NIDCM). Materials and Methods Approval was obtained from the local ethics committee. MR images from 453 patients with NIDCM and 150 healthy control subjects were included between 2005 and 2013 and were analyzed retrospectively. Myocardial contraction fraction (MCF) was calculated by dividing left ventricular (LV) stroke volume by LV myocardial volume, and long-axis strain (LAS) was calculated from the distances between the epicardial border of the LV apex and the midpoint of a line connecting the origins of the mitral valve leaflets at end systole and end diastole. Receiver operating characteristic curve, Kaplan-Meier method, Cox regression, and classification and regression tree (CART) analyses were performed for diagnostic and prognostic performances. Results LAS (area under the receiver operating characteristic curve [AUC] = 0.93, P < .001) and MCF (AUC = 0.92, P < .001) can be used to discriminate patients with NIDCM from age- and sex-matched control subjects. A total of 97 patients reached the combined end point during a median follow-up of 4.8 years. In multivariate Cox regression analysis, only LV ejection fraction (EF) and LAS independently indicated the combined end point (hazard ratio = 2.8 and 1.9, respectively; P < .001 for both). In a risk stratification approach with classification and regression tree analysis, combined LV EF and LAS cutoff values were used to stratify patients into three risk groups (log-rank test, P < .001). Conclusion Cardiovascular MR-derived MCF and LAS serve as reliable diagnostic and prognostic markers in patients with NIDCM. LAS, as a marker for longitudinal contractile function, is an independent parameter for outcome and offers incremental information beyond LV EF and the presence of myocardial fibrosis. © RSNA, 2017 Online supplemental material is available for this article.

High absolute basophil count is a powerful independent predictor of inferior overall survival in patients with primary myelofibrosis.

PubMed

Lucijanic, Marko; Livun, Ana; Stoos-Veic, Tajana; Pejsa, Vlatko; Jaksic, Ozren; Cicic, David; Lucijanic, Jelena; Romic, Zeljko; Orehovec, Biserka; Aralica, Gorana; Miletic, Marko; Kusec, Rajko

2018-05-01

To investigate the clinical and prognostic significance of absolute basophil count (ABC) in patients with primary myelofibrosis (PMF). We retrospectively investigated 58 patients with PMF treated in our institution in the period from 2006 to 2017. ABC was obtained in addition to other hematological and clinical parameters. Patients were separated into high and low ABC groups using the Receiver operating characteristic curve analysis. ABC was higher in PMF patients than in healthy controls (P < 0.001). Patients with high ABC had higher white blood cells (P < 0.001), higher red cell distribution width (P = 0.035), higher lactate dehydrogenase (P < 0.001), more frequently had circulatory blasts (P < 0.001), constitutional symptoms (P = 0.030) and massive splenomegaly (P = 0.014). ABC was also positively correlated with absolute monocyte count (AMC) (P < 0.001) and other components of differential blood count. There was no difference in ABC regarding driver mutations or degree of bone marrow fibrosis. Univariately, high ABC was significantly associated with inferior overall survival (hazard ratio (HR) 4.79, P < 0.001). This effect remained statistically significant (HR 4.27, P = 0.009) in a multivariate Cox regression model adjusted for age, gender, Dynamic International Prognostic Scoring System (HR 2.6, P = 0.001) and AMC (HR 8.45, P = 0.002). High ABC reflects higher disease activity and stronger proliferative potential of disease. ABC and AMC independently predict survival and therefore seem to reflect different underlying pathophysiologic processes. Hence, both have a potential for improvement of current prognostic scores. Basophils represent a part of malignant clone in PMF and are associated with unfavorable disease features and poor prognosis which is independent of currently established prognostic scoring system and monocytosis.

Characteristics of quantitative perfusion parameters on dynamic contrast‐enhanced MRI in mammographically occult breast cancer

PubMed Central

Ryu, Jung Kyu; Rhee, Sun Jung; Song, Jeong Yoon; Cho, Soo Hyun

2016-01-01

The purpose of this study was to compare the characteristics of quantitative perfusion parameters obtained from dynamic contrast‐enhanced (DCE) magnetic resonance imaging (MRI) in patients with mammographically occult (MO) breast cancers and those with mammographically visible (MV) breast cancers. Quantitative parameters (AUC, Ktrans,kep,ve,vp, and wi) from 13 MO breast cancers and 16 MV breast cancers were mapped after the DCE‐MRI data were acquired. Various prognostic factors, including axillary nodal status, estrogen receptor (ER), progesterone receptor (PR), Ki‐67, p53, E‐cadherin, and human epidermal growth factor receptor 2 (HER2) were obtained in each group. Fisher's exact test was used to compare any differences of the various prognostic factors between the two groups. The Mann‐Whitney U test was applied to compare the quantitative parameters between these two groups. Finally, Spearman's correlation was used to investigate the relationships between perfusion indices and four factors — age, tumor size, Ki‐67, and p53 — for each group. Although age, tumor size, and the prognostic factors were not statistically different between the two groups, the mean values of the quantitative parameters, except wi in the MV group, were higher than those in the MO group without statistical significance (p=0.219). The kep value was significantly different between the two groups (p=0.048), but the other parameters were not. In the MO group, vp with size, ve with p53, and Ktrans and vp with Ki‐67 had significant correlations (p<0.05). However, in the MV group, only kep showed significant correlation with age. The kep value was only the perfusion parameter of statistical significance between MO and MV breast cancers. PACS number(s): 87.19.U‐, 87.61.‐c PMID:27685105

Prognostic Biomarkers Used for Localised Prostate Cancer Management: A Systematic Review.

PubMed

Lamy, Pierre-Jean; Allory, Yves; Gauchez, Anne-Sophie; Asselain, Bernard; Beuzeboc, Philippe; de Cremoux, Patricia; Fontugne, Jacqueline; Georges, Agnès; Hennequin, Christophe; Lehmann-Che, Jacqueline; Massard, Christophe; Millet, Ingrid; Murez, Thibaut; Schlageter, Marie-Hélène; Rouvière, Olivier; Kassab-Chahmi, Diana; Rozet, François; Descotes, Jean-Luc; Rébillard, Xavier

2017-03-07

Prostate cancer stratification is based on tumour size, pretreatment PSA level, and Gleason score, but it remains imperfect. Current research focuses on the discovery and validation of novel prognostic biomarkers to improve the identification of patients at risk of aggressive cancer or of tumour relapse. This systematic review by the Intergroupe Coopérateur Francophone de Recherche en Onco-urologie (ICFuro) analysed new evidence on the analytical validity and clinical validity and utility of six prognostic biomarkers (PHI, 4Kscore, MiPS, GPS, Prolaris, Decipher). All available data for the six biomarkers published between January 2002 and April 2015 were systematically searched and reviewed. The main endpoints were aggressive prostate cancer prediction, additional value compared to classical prognostic parameters, and clinical benefit for patients with localised prostate cancer. The preanalytical and analytical validations were heterogeneous for all tests and often not adequate for the molecular signatures. Each biomarker was studied for specific indications (candidates for a first or second biopsy, and potential candidates for active surveillance, radical prostatectomy, or adjuvant treatment) for which the level of evidence (LOE) was variable. PHI and 4Kscore were the biomarkers with the highest LOE for discriminating aggressive and indolent tumours in different indications. Blood biomarkers (PHI and 4Kscore) have the highest LOE for the prediction of more aggressive prostate cancer and could help clinicians to manage patients with localised prostate cancer. The other biomarkers show a potential prognostic value; however, they should be evaluated in additional studies to confirm their clinical validity. We reviewed studies assessing the value of six prognostic biomarkers for prostate cancer. On the basis of the available evidence, some biomarkers could help in discriminating between aggressive and non-aggressive tumours with an additional value compared to the prognostic parameters currently used by clinicians. Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Towards evidence-based emergency medicine: best BETs from the Manchester Royal Infirmary. BET 4: Prognostic value of B-type natriuretic peptides (BNP and NT-proBNP) in community-acquired pneumonia.

PubMed

Hodgson, David; Nee, Patrick; Sultan, Laith

2012-10-01

A short cut review was carried out to establish the prognostic value of B-type natriuretic peptides (BNP and NT-proBNP) in community acquired pneumonia (CAP). Three cohort studies were directly relevant to the question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these papers are tabulated. The clinical bottom line was that B-type natriuretic peptides have prognostic value in CAP but further prospective studies were needed to assess their application in clinical practice.

Distributed Prognostics based on Structural Model Decomposition

NASA Technical Reports Server (NTRS)

Daigle, Matthew J.; Bregon, Anibal; Roychoudhury, I.

2014-01-01

Within systems health management, prognostics focuses on predicting the remaining useful life of a system. In the model-based prognostics paradigm, physics-based models are constructed that describe the operation of a system and how it fails. Such approaches consist of an estimation phase, in which the health state of the system is first identified, and a prediction phase, in which the health state is projected forward in time to determine the end of life. Centralized solutions to these problems are often computationally expensive, do not scale well as the size of the system grows, and introduce a single point of failure. In this paper, we propose a novel distributed model-based prognostics scheme that formally describes how to decompose both the estimation and prediction problems into independent local subproblems whose solutions may be easily composed into a global solution. The decomposition of the prognostics problem is achieved through structural decomposition of the underlying models. The decomposition algorithm creates from the global system model a set of local submodels suitable for prognostics. Independent local estimation and prediction problems are formed based on these local submodels, resulting in a scalable distributed prognostics approach that allows the local subproblems to be solved in parallel, thus offering increases in computational efficiency. Using a centrifugal pump as a case study, we perform a number of simulation-based experiments to demonstrate the distributed approach, compare the performance with a centralized approach, and establish its scalability. Index Terms-model-based prognostics, distributed prognostics, structural model decomposition ABBREVIATIONS

Clinicopathological factors associated with survival in patients with breast cancer brain metastasis.

PubMed

Li, Rong; Zhang, Kui; Siegal, Gene P; Wei, Shi

2017-06-01

Brain metastasis from breast cancer generally represents a catastrophic event yet demonstrates substantial biological heterogeneity. There have been limited studies solely focusing on the prognosis of patients with such metastasis. In this study, we carried out a comprehensive analysis in 108 consecutive patients with breast cancer brain metastases between 1997 and 2012 to further define clinicopathological factors associated with early onset of brain metastasis and survival outcomes after development of them. We found that lobular carcinoma, higher clinical stages at diagnosis, and lack of coexisting bone metastasis were significantly associated with a worse brain relapse-free survival when compared with brain-only metastasis. High histologic grade, triple-negative breast cancer, and absence of visceral involvement were unfavorable prognostic factors after brain metastasis. Furthermore, high histologic grade, advanced tumor stages, and lack of coexisting bone involvement indicated a worse overall survival. Thus, the previously established prognostic factors in early stage or advanced breast cancers may not entirely apply to patients with brain metastases. Furthermore, the prognostic significance of the clinicopathological factors differed before and after a patient develops brain metastasis. This knowledge might help in establishing an algorithm to further stratify patients with breast cancer into prognostically significant categories for optimal prevention, screening, and treatment of their brain metastasis. Copyright © 2017 Elsevier Inc. All rights reserved.

The Prognostic Influence of BRAF Mutation and other Molecular, Clinical and Laboratory Parameters in Stage IV Colorectal Cancer.

PubMed

Karadima, Maria L; Saetta, Angelica A; Chatziandreou, Ilenia; Lazaris, Andreas C; Patsouris, Efstratios; Tsavaris, Nikolaos

2016-10-01

Our aim was to evaluate the predictive and prognostic influence of BRAF mutation and other molecular, clinical and laboratory parameters in stage IV colorectal cancer (CRC). 60 patients were included in this retrospective analysis, and 17 variables were examined for their relation with treatment response and survival. KRAS mutation was identified in 40.3 % of cases, BRAF and PIK3CA in 8.8 % and 10.5 % respectively. 29.8 % of patients responded to treatment. Median survival time was 14.3 months. Weight loss, fever, abdominal metastases, blood transfusion, hypoalbuminaimia, BRAF and PIK3CA mutations, CRP and DNA Index were associated with survival. In multivariate analysis, male patients had 3.8 times higher probability of response, increased DNA Index was inversely correlated with response and one unit raise of DNA Index augmented 6 times the probability of death. Our findings potentiate the prognostic role of BRAF, PIK3CA mutations and ploidy in advanced CRC.

Glycolytic activity in breast cancer using 18F-FDG PET/CT as prognostic predictor: A molecular phenotype approach.

PubMed

Garcia Vicente, A M; Soriano Castrejón, A; Amo-Salas, M; Lopez Fidalgo, J F; Muñoz Sanchez, M M; Alvarez Cabellos, R; Espinosa Aunion, R; Muñoz Madero, V

2016-01-01

To explore the relationship between basal (18)F-FDG uptake in breast tumors and survival in patients with breast cancer (BC) using a molecular phenotype approach. This prospective and multicentre study included 193 women diagnosed with BC. All patients underwent an (18)F-FDG PET/CT prior to treatment. Maximum standardized uptake value (SUVmax) in tumor (T), lymph nodes (N), and the N/T index was obtained in all the cases. Metabolic stage was established. As regards biological prognostic parameters, tumors were classified into molecular sub-types and risk categories. Overall survival (OS) and disease free survival (DFS) were obtained. An analysis was performed on the relationship between semi-quantitative metabolic parameters with molecular phenotypes and risk categories. The effect of molecular sub-type and risk categories in prognosis was analyzed using Kaplan-Meier and univariate and multivariate tests. Statistical differences were found in both SUVT and SUVN, according to the molecular sub-types and risk classifications, with higher semi-quantitative values in more biologically aggressive tumors. No statistical differences were observed with respect to the N/T index. Kaplan-Meier analysis revealed that risk categories were significantly related to DFS and OS. In the multivariate analysis, metabolic stage and risk phenotype showed a significant association with DFS. High-risk phenotype category showed a worst prognosis with respect to the other categories with higher SUVmax in primary tumor and lymph nodes. Copyright © 2015 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

Metrics for Offline Evaluation of Prognostic Performance

NASA Technical Reports Server (NTRS)

Saxena, Abhinav; Celaya, Jose; Saha, Bhaskar; Saha, Sankalita; Goebel, Kai

2010-01-01

Prognostic performance evaluation has gained significant attention in the past few years. Currently, prognostics concepts lack standard definitions and suffer from ambiguous and inconsistent interpretations. This lack of standards is in part due to the varied end-user requirements for different applications, time scales, available information, domain dynamics, etc. to name a few. The research community has used a variety of metrics largely based on convenience and their respective requirements. Very little attention has been focused on establishing a standardized approach to compare different efforts. This paper presents several new evaluation metrics tailored for prognostics that were recently introduced and were shown to effectively evaluate various algorithms as compared to other conventional metrics. Specifically, this paper presents a detailed discussion on how these metrics should be interpreted and used. These metrics have the capability of incorporating probabilistic uncertainty estimates from prognostic algorithms. In addition to quantitative assessment they also offer a comprehensive visual perspective that can be used in designing the prognostic system. Several methods are suggested to customize these metrics for different applications. Guidelines are provided to help choose one method over another based on distribution characteristics. Various issues faced by prognostics and its performance evaluation are discussed followed by a formal notational framework to help standardize subsequent developments.

Prognostics for Ground Support Systems: Case Study on Pneumatic Valves

NASA Technical Reports Server (NTRS)

Daigle, Matthew; Goebel, Kai

2011-01-01

Prognostics technologies determine the health (or damage) state of a component or sub-system, and make end of life (EOL) and remaining useful life (RUL) predictions. Such information enables system operators to make informed maintenance decisions and streamline operational and mission-level activities. We develop a model-based prognostics methodology for pneumatic valves used in ground support equipment for cryogenic propellant loading operations. These valves are used to control the flow of propellant, so failures may have a significant impact on launch availability. Therefore, correctly predicting when valves will fail enables timely maintenance that avoids launch delays and aborts. The approach utilizes mathematical models describing the underlying physics of valve degradation, and, employing the particle filtering algorithm for joint state-parameter estimation, determines the health state of the valve and the rate of damage progression, from which EOL and RUL predictions are made. We develop a prototype user interface for valve prognostics, and demonstrate the prognostics approach using historical pneumatic valve data from the Space Shuttle refueling system.

Neuroendocrine tumors of colon and rectum: validation of clinical and prognostic values of the World Health Organization 2010 grading classifications and European Neuroendocrine Tumor Society staging systems.

PubMed

Shen, Chaoyong; Yin, Yuan; Chen, Huijiao; Tang, Sumin; Yin, Xiaonan; Zhou, Zongguang; Zhang, Bo; Chen, Zhixin

2017-03-28

This study evaluated and compared the clinical and prognostic values of the grading criteria used by the World Health Organization (WHO) and the European Neuroendocrine Tumors Society (ENETS). Moreover, this work assessed the current best prognostic model for colorectal neuroendocrine tumors (CRNETs). The 2010 WHO classifications and the ENETS systems can both stratify the patients into prognostic groups, although the 2010 WHO criteria is more applicable to CRNET patients. Along with tumor location, the 2010 WHO criteria are important independent prognostic parameters for CRNETs in both univariate and multivariate analyses through Cox regression (P<0.05). Data from 192 consecutive patients histopathologically diagnosed with CRNETs and had undergone surgical resection from January 2009 to May 2016 in a single center were retrospectively analyzed. Findings suggest that the WHO classifications are superior over the ENETS classification system in predicting the prognosis of CRNETs. Additionally, the WHO classifications can be widely used in clinical practice.

Prognostic value of platelet-derived growth factor-A (PDGF-A) in gastric carcinoma.

PubMed Central

Katano, M; Nakamura, M; Fujimoto, K; Miyazaki, K; Morisaki, T

1998-01-01

OBJECTIVE: Because our previous study indicated that PDGF-A mRNA expression in biopsy specimens might identify a subgroup of high-risk patients with gastric carcinoma, in this study we analyzed the prognostic value of platelet-derived growth factor-A (PDGF-A) gene expression in gastric carcinoma biopsy specimens. METHODS: Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to analyze the PDGF-A gene expression in 65 gastric carcinoma endoscopic biopsy specimens. The 65 patients were divided into a PDGF-A-positive group (29 patients) and a PDGF-A-negative group (36 patients). RESULTS: On the basis of 2-year follow-up data, the PDGF-A-positive group demonstrated a shorter overall survival rate compared with the PDGF-A-negative group (p < 0.0001). A similar correlation was found in 34 advanced-stage patients (p = 0.003) and in 24 advanced-stage patients who underwent a curative resection (p = 0.003). Multivariance analysis indicated that the transcription of PDGF-A gene is a potent prognostic factor that is independent of the traditional pathologic parameters. CONCLUSIONS: Expression of PDGF-A mRNA in gastric biopsy specimens may be a new preoperative prognostic parameter in gastric carcinoma. Images Figure 1. Figure 5. PMID:9527059

Whole-tumour diffusion kurtosis MR imaging histogram analysis of rectal adenocarcinoma: Correlation with clinical pathologic prognostic factors.

PubMed

Cui, Yanfen; Yang, Xiaotang; Du, Xiaosong; Zhuo, Zhizheng; Xin, Lei; Cheng, Xintao

2018-04-01

To investigate potential relationships between diffusion kurtosis imaging (DKI)-derived parameters using whole-tumour volume histogram analysis and clinicopathological prognostic factors in patients with rectal adenocarcinoma. 79 consecutive patients who underwent MRI examination with rectal adenocarcinoma were retrospectively evaluated. Parameters D, K and conventional ADC were measured using whole-tumour volume histogram analysis. Student's t-test or Mann-Whitney U-test, receiver operating characteristic curves and Spearman's correlation were used for statistical analysis. Almost all the percentile metrics of K were correlated positively with nodal involvement, higher histological grades, the presence of lymphangiovascular invasion (LVI) and circumferential margin (CRM) (p<0.05), with the exception of between K 10th , K 90th and histological grades. In contrast, significant negative correlations were observed between 25th, 50th percentiles and mean values of ADC and D, as well as ADC 10th , with tumour T stages (p< 0.05). Meanwhile, lower 75th and 90th percentiles of ADC and D values were also correlated inversely with nodal involvement (p< 0.05). K mean showed a relatively higher area under the curve (AUC) and higher specificity than other percentiles for differentiation of lesions with nodal involvement. DKI metrics with whole-tumour volume histogram analysis, especially K parameters, were associated with important prognostic factors of rectal cancer. • K correlated positively with some important prognostic factors of rectal cancer. • K mean showed higher AUC and specificity for differentiation of nodal involvement. • DKI metrics with whole-tumour volume histogram analysis depicted tumour heterogeneity.

The prognostic value of T1 mapping and late gadolinium enhancement cardiovascular magnetic resonance imaging in patients with light chain amyloidosis.

PubMed

Lin, Lu; Li, Xiao; Feng, Jun; Shen, Kai-Ni; Tian, Zhuang; Sun, Jian; Mao, Yue-Ying; Cao, Jian; Jin, Zheng-Yu; Li, Jian; Selvanayagam, Joseph B; Wang, Yi-Ning

2018-01-03

Cardiac impairment is associated with high morbidity and mortality in immunoglobulin light chain (AL) type amyloidosis, for which early identification and risk stratification is vital. For myocardial tissue characterization, late gadolinium enhancement (LGE) is a classic and most commonly performed cardiovascular magnetic resonance (CMR) parameter. T1 mapping with native T1 and extracellular volume (ECV) are recently developed quantitative parameters. We aimed to investigate the prognostic value of native T1, ECV and LGE in patients with AL amyloidosis. Eighty-two patients (55.5 ± 8.5 years; 52 M) and 20 healthy subjects (53.2 ± 11.7 years; 10 M) were prospectively recruited. All subjects underwent CMR with LGE imaging and T1 mapping using a Modified Look-Locker Inversion-recovery (MOLLI) sequence on a 3 T scanner. Native T1 and ECV were measured semi-automatically using a dedicated CMR software. The left ventricular (LV) LGE pattern was classified as none, patchy, and global groups. Global LGE was considered when there was diffuse, transmural LGE in more than half of the short axis images. Follow-up was performed for all-cause mortality using Cox proportional hazards regression analysis and Kaplan-Meier survival curves. The patients demonstrated an increase in native T1 (1438 ± 120 ms vs. 1283 ± 46 ms, P = 0.001) and ECV (43.9 ± 10.9% vs. 27.0 ± 1.7%, P = 0.001) compared to healthy controls. Native T1, ECV and LGE showed significant correlation with Mayo Stage, and ECV and LGE showed significant correlation with echocardiographic E/E' and LV ejection fraction. During the follow-up for a median time of 8 months, 21 deaths occurred. ECV ≥ 44.0% (hazard ratio [HR] 7.249, 95% confidence interval (CI) 1.751-13.179, P = 0.002) and global LGE (HR 4.804, 95% CI 1.971-12.926, P = 0.001) were independently prognostic for mortality over other clinical and imaging parameters. In subgroups with the same LGE pattern, ECV ≥ 44.0% remained prognostic (log rank P = 0.029). Median native T1 (1456 ms) was not prognostic for mortality (Tarone-Ware, P = 0.069). During a short-term follow-up, both ECV and LGE are independently prognostic for mortality in AL amyloidosis. In patients with a similar LGE pattern, ECV remained prognostic. Native T1 was not found to be a prognostic factor.

The prognostic and predictive value of vascular response parameters measured by dynamic contrast-enhanced-CT, -MRI and -US in patients with metastatic renal cell carcinoma receiving sunitinib.

PubMed

Hudson, John M; Bailey, Colleen; Atri, Mostafa; Stanisz, Greg; Milot, Laurent; Williams, Ross; Kiss, Alex; Burns, Peter N; Bjarnason, Georg A

2018-06-01

To identify dynamic contrast-enhanced (DCE) imaging parameters from MRI, CT and US that are prognostic and predictive in patients with metastatic renal cell cancer (mRCC) receiving sunitinib. Thirty-four patients were monitored by DCE imaging on day 0 and 14 of the first course of sunitinib treatment. Additional scans were performed with DCE-US only (day 7 or 28 and 2 weeks after the treatment break). Perfusion parameters that demonstrated a significant correlation (Spearman p < 0.05) with progression-free survival (PFS) and overall survival (OS) were investigated using Cox proportional hazard models/ratios (HR) and Kaplan-Meier survival analysis. A higher baseline and day 14 value for Ktrans (DCE-MRI) and a lower pre-treatment vascular heterogeneity (DCE-US) were significantly associated with a longer PFS (HR, 0.62, 0.37 and 5.5, respectively). A larger per cent decrease in blood volume on day 14 (DCE-US) predicted a longer OS (HR, 1.45). We did not find significant correlations between any of the DCE-CT parameters and PFS/OS, unless a cut-off analysis was used. DCE-MRI, -CT and ultrasound produce complementary parameters that reflect the prognosis of patients receiving sunitinib for mRCC. Blood volume measured by DCE-US was the only parameter whose change during early anti-angiogenic therapy predicted for OS and PFS. • DCE-CT, -MRI and ultrasound are complementary modalities for monitoring anti-angiogenic therapy. • The change in blood volume measured by DCE-US was predictive of OS/PFS. • Baseline vascular heterogeneity by DCE-US has the strongest prognostic value for PFS.

Heart rate variability.

PubMed

Cygankiewicz, Iwona; Zareba, Wojciech

2013-01-01

Heart rate variability (HRV) provides indirect insight into autonomic nervous system tone, and has a well-established role as a marker of cardiovascular risk. Recent decades brought an increasing interest in HRV assessment as a diagnostic tool in detection of autonomic impairment, and prediction of prognosis in several neurological disorders. Both bedside analysis of simple markers of HRV, as well as more sophisticated HRV analyses including time, frequency domain and nonlinear analysis have been proven to detect early autonomic involvement in several neurological disorders. Furthermore, altered HRV parameters were shown to be related with cardiovascular risk, including sudden cardiac risk, in patients with neurological diseases. This chapter aims to review clinical and prognostic application of HRV analysis in diabetes, stroke, multiple sclerosis, muscular dystrophies, Parkinson's disease and epilepsy. © 2013 Elsevier B.V. All rights reserved.

Clinical Utility of Quantitative Gleason Grading in Prostate Biopsies and Prostatectomy Specimens.

PubMed

Sauter, Guido; Steurer, Stefan; Clauditz, Till Sebastian; Krech, Till; Wittmer, Corinna; Lutz, Florian; Lennartz, Maximilian; Janssen, Tim; Hakimi, Nayira; Simon, Ronald; von Petersdorff-Campen, Mareike; Jacobsen, Frank; von Loga, Katharina; Wilczak, Waldemar; Minner, Sarah; Tsourlakis, Maria Christina; Chirico, Viktoria; Haese, Alexander; Heinzer, Hans; Beyer, Burkhard; Graefen, Markus; Michl, Uwe; Salomon, Georg; Steuber, Thomas; Budäus, Lars Henrik; Hekeler, Elena; Malsy-Mink, Julia; Kutzera, Sven; Fraune, Christoph; Göbel, Cosima; Huland, Hartwig; Schlomm, Thorsten

2016-04-01

Gleason grading is the strongest prognostic parameter in prostate cancer. Gleason grading is categorized as Gleason ≤ 6, 3 + 4, 4 + 3, 8, and 9-10, but there is variability within these subgroups. For example, Gleason 4 components may range from 5-45% in a Gleason 3 + 4 = 7 cancer. To assess the clinical relevance of the fractions of Gleason patterns. Prostatectomy specimens from 12823 consecutive patients and of 2971 matched preoperative biopsies for which clinical data with an annual follow-up between 2005 and 2014 were available from the Martini-Klinik database. To evaluate the utility of quantitative grading, the fraction of Gleason 3, 4, and 5 patterns seen in biopsies and prostatectomies were recorded. Gleason grade fractions were compared with prostatectomy findings and prostate-specific antigen recurrence. Our data suggest a striking utility of quantitative Gleason grading. In prostatectomy specimens, there was a continuous increase of the risk of prostate-specific antigen recurrence with increasing percentage of Gleason 4 fractions with remarkably small differences in outcome at clinically important thresholds (0% vs 5%; 40% vs 60% Gleason 4), distinguishing traditionally established prognostic groups. Also, in biopsies, the quantitative Gleason scoring identified various intermediate risk groups with respect to Gleason findings in corresponding prostatectomies. Quantitative grading may also reduce the clinical impact of interobserver variability because borderline findings such as tumors with 5%, 40%, or 60% Gleason 4 fractions and very small Gleason 5 fractions (with pivotal impact on the Gleason score) are disclaimed. Quantitative Gleason pattern data should routinely be provided in addition to Gleason score categories, both in biopsies and in prostatectomy specimens. Gleason score is the most important prognostic parameter in prostate cancer, but prone to interobserver variation. The results of our study show that morphological aspects that define the Gleason grade in prostate cancer represent a continuum. Quantitation of Gleason patterns provides clinically relevant information beyond the traditional Gleason grading categories ≤ 3 + 3, 3 + 4, 4 + 3, 8, 9 -1 0. Quantitative Gleason scoring can help to minimize variations between different pathologists and substantially aid in optimized therapy decision-making. Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Diagnostic and Prognostic Value of CMR T1-Mapping in Patients With Heart Failure and Preserved Ejection Fraction.

PubMed

Rommel, Karl-Philipp; Lücke, Christian; Lurz, Philipp

2017-10-01

Heart failure with preserved ejection fraction (HFpEF) presents a major challenge in modern cardiology. Although this syndrome is of increasing prevalence and is associated with unfavorable outcomes, treatment trials have failed to establish effective therapies. Currently, solutions to this dilemma are being investigated, including categorizing and characterizing patients more diversely to individualize treatment. In this regard, new imaging techniques might provide important information. Diastolic dysfunction is a diagnostic and pathophysiological cornerstone in HFpEF and is believed to be caused by systemic inflammation with the development of interstitial myocardial fibrosis and myocardial stiffening. Cardiac magnetic resonance (CMR) T 1 -mapping is a novel tool, which allows noninvasive quantification of the extracellular space and diffuse myocardial fibrosis. This review provides an overview of the potential of myocardial tissue characterization with CMR T 1 mapping in HFpEF patients, outlining its diagnostic and prognostic implications and discussing future directions. We conclude that CMR T 1 mapping is potentially an effective tool for patient characterization in large-scale epidemiological, diagnostic, and therapeutic HFpEF trials beyond traditional imaging parameters. Copyright © 2017 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

The preoperative plasma fibrinogen level is an independent prognostic factor for overall survival of breast cancer patients who underwent surgical treatment.

PubMed

Wen, Jiahuai; Yang, Yanning; Ye, Feng; Huang, Xiaojia; Li, Shuaijie; Wang, Qiong; Xie, Xiaoming

2015-12-01

Previous studies have suggested that plasma fibrinogen contributes to tumor cell proliferation, progression and metastasis. The current study was performed to evaluate the prognostic relevance of preoperative plasma fibrinogen in breast cancer patients. Data of 2073 consecutive breast cancer patients, who underwent surgery between January 2002 and December 2008 at the Sun Yat-sen University Cancer Center, were retrospectively evaluated. Plasma fibrinogen levels were routinely measured before surgeries. Participants were grouped by the cutoff value estimated by the receiver operating characteristic (ROC) curve analysis. Overall survival (OS) was assessed using Kaplan-Meier analysis, and multivariate Cox proportional hazards regression model was performed to evaluate the independent prognostic value of plasma fibrinogen level. The optimal cutoff value of preoperative plasma fibrinogen was determined to be 2.83 g/L. The Kaplan-Meier analysis showed that patients with high fibrinogen levels had shorter OS than patients with low fibrinogen levels (p < 0.001). Multivariate analysis suggested preoperative plasma fibrinogen as an independent prognostic factor for OS in breast cancer patients (HR = 1.475, 95% confidence interval (CI): 1.177-1.848, p = 0.001). Subgroup analyses revealed that plasma fibrinogen level was an unfavorable prognostic parameter in stage II-III, Luminal subtypes and triple-negative breast cancer patients. Elevated preoperative plasma fibrinogen was independently associated with poor prognosis in breast cancer patients and may serve as a valuable parameter for risk assessment in breast cancer patients. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Expression of p40 (∆Np63) protein in meningiomas, an unexpected finding: immunohistochemical study and evaluation of its possible prognostic role.

PubMed

Guadagno, Elia; Del Basso De Caro, Marialaura; Pignatiello, Sara; Sciammarella, Concetta; Solari, Domenico; Cappabianca, Paolo; Maiuri, Francesco; Dones, Flavia

2016-09-01

According to the 2007 WHO (World Health Organization) Classification, meningiomas are divided into three grades of malignancy, with different recurrence rate, based exclusively on histopathological parameters. Loss/reduction of PgR (Progesterone Receptor) expression and increased Ki67 L.I. (Labeling Index) have been proven as possible prognostic factors able to predict the relapse of the disease. However, they sometimes result unreliable, especially when discordant. p40 is the short form of the p53 homologue gene p63, also named ∆Np63, and its antibody has recently been introduced as a highly specific diagnostic marker of the squamous cell carcinoma of the lung. Nevertheless its expression has been found in many other unconventional sites (e.g. placenta, urotheluim, etc). Herein we assessed the immuno-expression of p40 protein in a series of 72 meningiomas (35 grade I and 37 grade II) and analyzed its correlation with clinicopathological parameters, overall survival and recurrence free interval. We found that a high p40 score correlated with high histological grade, presence of recurrence, increased Ki67 L.I. and loss/reduction of PgR signal. Moreover, a higher expression of p40 was shown to be a significant prognostic factor for the development of recurrences and resulted a prognostic independent variable in multivariate analysis. Overall, for the first time, we investigated the expression of p40 protein in meningiomas and explored its usefulness as prognostic marker in addition to PgR and Ki67 L.I.

Prognostic and clinicopathological significance of long noncoding RNA HOXA11-AS expression in human solid tumors: a meta-analysis.

PubMed

Mu, Shidai; Ai, Lisha; Fan, Fengjuan; Sun, Chunyan; Hu, Yu

2018-01-01

Recent studies have emphasized the important prognostic role of long noncoding RNAs (lncRNAs) in various types of cancers. Here we conducted a meta-analysis to investigate whether lncRNA HOXA11-AS can be served as a prognostic biomarker in human cancers. We systematically searched PubMed, Embase, ISI Web of Science, and SCOPUS for relevant studies, to investigate the prognostic significance of HOXA11-AS expression in cancer patients. Odds ratios (ORs) or hazards ratios (HRs) with corresponding 95% confidence intervals (CIs) are pooled to estimate the association between HOXA11-AS expression and clinicopathological parameters or survival of cancer patients. A total of eight eligible studies with 1320 cancer patients were enrolled in our meta-analysis. The results revealed that increased expression level of HOXA11-AS was significantly associated with clinicopathological parameters including more lymph node metastasis (OR = 2.06, 95% CI 1.31-3.25), advanced tumor stage (OR = 4.22, 95% CI 2.60-6.85), as well as poor tumor differentiation (OR = 2.49, 95 CI 1.47-4.20), but not correlated with age ( p  = 0.101) or gender ( p  = 0.845). In addition, cancer patients with high HOXA11-AS are prognosed to have shorter OS (pooled HR = 1.86, 95% CI 1.39-2.48) and PFS (pooled HR = 2.47, 95% CI 1.29-4.75). HOXA11-AS overexpression might be a convinced unfavorable prognostic factor that helps the clinical decision-making process.

Multivariate meta-analysis of prognostic factor studies with multiple cut-points and/or methods of measurement.

PubMed

Riley, Richard D; Elia, Eleni G; Malin, Gemma; Hemming, Karla; Price, Malcolm P

2015-07-30

A prognostic factor is any measure that is associated with the risk of future health outcomes in those with existing disease. Often, the prognostic ability of a factor is evaluated in multiple studies. However, meta-analysis is difficult because primary studies often use different methods of measurement and/or different cut-points to dichotomise continuous factors into 'high' and 'low' groups; selective reporting is also common. We illustrate how multivariate random effects meta-analysis models can accommodate multiple prognostic effect estimates from the same study, relating to multiple cut-points and/or methods of measurement. The models account for within-study and between-study correlations, which utilises more information and reduces the impact of unreported cut-points and/or measurement methods in some studies. The applicability of the approach is improved with individual participant data and by assuming a functional relationship between prognostic effect and cut-point to reduce the number of unknown parameters. The models provide important inferential results for each cut-point and method of measurement, including the summary prognostic effect, the between-study variance and a 95% prediction interval for the prognostic effect in new populations. Two applications are presented. The first reveals that, in a multivariate meta-analysis using published results, the Apgar score is prognostic of neonatal mortality but effect sizes are smaller at most cut-points than previously thought. In the second, a multivariate meta-analysis of two methods of measurement provides weak evidence that microvessel density is prognostic of mortality in lung cancer, even when individual participant data are available so that a continuous prognostic trend is examined (rather than cut-points). © 2015 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.

Correlation Between Magnetic Resonance Imaging-Based Evaluation of Extramural Vascular Invasion and Prognostic Parameters of T3 Stage Rectal Cancer.

PubMed

Yu, Jing; Huang, Dong-Ya; Xu, Hui-Xin; Li, Yang; Xu, Qing

2016-01-01

The aim of this study was to analyze the correlation between magnetic resonance imaging-based extramural vascular invasion (EMVI) and the prognostic clinical and histological parameters of stage T3 rectal cancers. Eighty-six patients with T3 stage rectal cancer who received surgical resection without neoadjuvant therapy were included. Magnetic resonance imaging-based EMVI scores were determined. Correlations between the scores and pretreatment carcinoembryonic antigen levels, tumor differentiation grade, nodal stage, and vascular endothelial growth factor expression were analyzed using Spearman rank coefficient analysis. Magnetic resonance imaging-based EMVI scores were statistically different (P = 0.001) between histological nodal stages (N0 vs N1 vs N2). Correlations were found between magnetic resonance imaging-based EMVI scores and tumor histological grade (rs = 0.227, P = 0.035), histological nodal stage (rs = 0.524, P < 0.001), and vascular endothelial growth factor expression (rs = 0.422; P = 0.016). Magnetic resonance imaging-based EMVI score is correlated with prognostic parameters of T3 stage rectal cancers and has the potential to become an imaging biomarker of tumor aggressiveness. Magnetic resonance imaging-based EMVI may be useful in helping the multidisciplinary team to stratify T3 rectal cancer patients for neoadjuvant therapies.

The correlation of extranodal invasion with other prognostic parameters in lymph node positive breast cancer.

PubMed

Altinyollar, Hüseyin; Berberoğlu, Uğur; Gülben, Kaptan; Irkin, Fikret

2007-06-01

The presence of extranodal invasion (ENI) in the metastatic lymph nodes is reported to increase the risk of locoregional recurrence while shortening disease-free and overall survival in patients with breast cancer. In this study the relationship between ENI and other prognostic parameters and survival is investigated. Of 650 patients with breast cancer who were treated in Ankara Oncology Teaching and Research Hospital from 1996 to 2003, 368 (56.6%) had lymph node metastasis. The patients with axillary metastasis were separated into two groups as with and without invasion to lymph node capsule and the surrounding adipose tissue. Clinicopathologic features were analyzed by univariate and multivariate logistic regression. Of 368 patients with axillary metastasis, 135 (36.7%) had ENI. Based on multivariate analysis; the number of metastatic lymph nodes, lymphatic invasion, and tumor necrosis were found to be related with ENI. In the group with ENI, 5-year overall survival rate was 74.8%, compared to 82.3% for patients without ENI which was significantly lower (P = 0.04). In lymph node positive breast cancer with presence of ENI, adverse prognostic parameters are more frequently encountered and has a worse overall survival compared to group without ENI. (c) 2007 Wiley-Liss, Inc.

Combined DNA methylation and gene expression profiling in gastrointestinal stromal tumors reveals hypomethylation of SPP1 as an independent prognostic factor.

PubMed

Haller, Florian; Zhang, Jitao David; Moskalev, Evgeny A; Braun, Alexander; Otto, Claudia; Geddert, Helene; Riazalhosseini, Yasser; Ward, Aoife; Balwierz, Aleksandra; Schaefer, Inga-Marie; Cameron, Silke; Ghadimi, B Michael; Agaimy, Abbas; Fletcher, Jonathan A; Hoheisel, Jörg; Hartmann, Arndt; Werner, Martin; Wiemann, Stefan; Sahin, Ozgür

2015-03-01

Gastrointestinal stromal tumors (GISTs) have distinct gene expression patterns according to localization, genotype and aggressiveness. DNA methylation at CpG dinucleotides is an important mechanism for regulation of gene expression. We performed targeted DNA methylation analysis of 1.505 CpG loci in 807 cancer-related genes in a cohort of 76 GISTs, combined with genome-wide mRNA expression analysis in 22 GISTs, to identify signatures associated with clinicopathological parameters and prognosis. Principal component analysis revealed distinct DNA methylation patterns associated with anatomical localization, genotype, mitotic counts and clinical follow-up. Methylation of a single CpG dinucleotide in the non-CpG island promoter of SPP1 was significantly correlated with shorter disease-free survival. Hypomethylation of this CpG was an independent prognostic parameter in a multivariate analysis compared to anatomical localization, genotype, tumor size and mitotic counts in a cohort of 141 GISTs with clinical follow-up. The epigenetic regulation of SPP1 was confirmed in vitro, and the functional impact of SPP1 protein on tumorigenesis-related signaling pathways was demonstrated. In summary, SPP1 promoter methylation is a novel and independent prognostic parameter in GISTs, and might be helpful in estimating the aggressiveness of GISTs from the intermediate-risk category. © 2014 UICC.

Echocardiography and risk prediction in advanced heart failure: incremental value over clinical markers.

PubMed

Agha, Syed A; Kalogeropoulos, Andreas P; Shih, Jeffrey; Georgiopoulou, Vasiliki V; Giamouzis, Grigorios; Anarado, Perry; Mangalat, Deepa; Hussain, Imad; Book, Wendy; Laskar, Sonjoy; Smith, Andrew L; Martin, Randolph; Butler, Javed

2009-09-01

Incremental value of echocardiography over clinical parameters for outcome prediction in advanced heart failure (HF) is not well established. We evaluated 223 patients with advanced HF receiving optimal therapy (91.9% angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, 92.8% beta-blockers, 71.8% biventricular pacemaker, and/or defibrillator use). The Seattle Heart Failure Model (SHFM) was used as the reference clinical risk prediction scheme. The incremental value of echocardiographic parameters for event prediction (death or urgent heart transplantation) was measured by the improvement in fit and discrimination achieved by addition of standard echocardiographic parameters to the SHFM. After a median follow-up of 2.4 years, there were 38 (17.0%) events (35 deaths; 3 urgent transplants). The SHFM had likelihood ratio (LR) chi(2) 32.0 and C statistic 0.756 for event prediction. Left ventricular end-systolic volume, stroke volume, and severe tricuspid regurgitation were independent echocardiographic predictors of events. The addition of these parameters to SHFM improved LR chi(2) to 72.0 and C statistic to 0.866 (P < .001 and P=.019, respectively). Reclassifying the SHFM-predicted risk with use of the echocardiography-added model resulted in improved prognostic separation. Addition of standard echocardiographic variables to the SHFM results in significant improvement in risk prediction for patients with advanced HF.

Overcoming intratumoural heterogeneity for reproducible molecular risk stratification: a case study in advanced kidney cancer.

PubMed

Lubbock, Alexander L R; Stewart, Grant D; O'Mahony, Fiach C; Laird, Alexander; Mullen, Peter; O'Donnell, Marie; Powles, Thomas; Harrison, David J; Overton, Ian M

2017-06-26

Metastatic clear cell renal cell cancer (mccRCC) portends a poor prognosis and urgently requires better clinical tools for prognostication as well as for prediction of response to treatment. Considerable investment in molecular risk stratification has sought to overcome the performance ceiling encountered by methods restricted to traditional clinical parameters. However, replication of results has proven challenging, and intratumoural heterogeneity (ITH) may confound attempts at tissue-based stratification. We investigated the influence of confounding ITH on the performance of a novel molecular prognostic model, enabled by pathologist-guided multiregion sampling (n = 183) of geographically separated mccRCC cohorts from the SuMR trial (development, n = 22) and the SCOTRRCC study (validation, n = 22). Tumour protein levels quantified by reverse phase protein array (RPPA) were investigated alongside clinical variables. Regularised wrapper selection identified features for Cox multivariate analysis with overall survival as the primary endpoint. The optimal subset of variables in the final stratification model consisted of N-cadherin, EPCAM, Age, mTOR (NEAT). Risk groups from NEAT had a markedly different prognosis in the validation cohort (log-rank p = 7.62 × 10 -7 ; hazard ratio (HR) 37.9, 95% confidence interval 4.1-353.8) and 2-year survival rates (accuracy = 82%, Matthews correlation coefficient = 0.62). Comparisons with established clinico-pathological scores suggest favourable performance for NEAT (Net reclassification improvement 7.1% vs International Metastatic Database Consortium score, 25.4% vs Memorial Sloan Kettering Cancer Center score). Limitations include the relatively small cohorts and associated wide confidence intervals on predictive performance. Our multiregion sampling approach enabled investigation of NEAT validation when limiting the number of samples analysed per tumour, which significantly degraded performance. Indeed, sample selection could change risk group assignment for 64% of patients, and prognostication with one sample per patient performed only slightly better than random expectation (median logHR = 0.109). Low grade tissue was associated with 3.5-fold greater variation in predicted risk than high grade (p = 0.044). This case study in mccRCC quantitatively demonstrates the critical importance of tumour sampling for the success of molecular biomarker studies research where ITH is a factor. The NEAT model shows promise for mccRCC prognostication and warrants follow-up in larger cohorts. Our work evidences actionable parameters to guide sample collection (tumour coverage, size, grade) to inform the development of reproducible molecular risk stratification methods.

Prognostic predictive value of preoperative intratumoral 2-deoxy-2-(18F)fluoro-D-glucose uptake heterogeneity in patients with high-grade serous ovarian cancer.

PubMed

Liu, Shuai; Feng, Zheng; Jiang, Zhaoxia; Wen, Hao; Xu, Junyan; Pan, Herong; Deng, Yu; Zhang, Lei; Ju, Xingzhu; Chen, Xiaojun; Wu, Xiaohua

2018-05-16

This study aimed to explore the clinical and prognostic significance of pretreatment positron-emission tomography/computed tomography (PET/CT) parameters, especially 2-deoxy-2-(F)fluoro-D-glucose-based heterogeneity, in high-grade serous ovarian cancer (HGSC). We retrospectively investigated 56 patients with HGSC who underwent PET/CT before primary surgery at our hospital between January 2010 and June 2015. None of these patients received neoadjuvant chemotherapy. PET/CT parameters, including maximum and mean standardized uptake value (SUVmax and SUVmean), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and intratumoral heterogeneity index (HI), were measured for all patients. Differences of each PET/CT parameter between primary tumors (-P) and omental metastatic lesions (-M) were compared by paired t tests. Progression-free survival (PFS) and overall survival were analyzed by the Kaplan-Meier method and log-rank tests in univariate analyses. Cox regression analyses were used for multivariate analysis. SUVmean-P was higher than SUVmean-M (P=0.001). However, there were no statistical differences of SUVmax, MTV, TLG, or HI between primary and omental lesions. Chemosensitive patients tended to have higher levels of SUVmax-P (P=0.011), MTV-P (P=0.014), TLG-P (P=0.035), and HI-P (P=0.002), respectively. In univariate analyses, higher HI-P was associated with better PFS (P=0.007). However, in multivariate analysis, HI-P was not an independent predictor of PFS (P=0.581). Neither HI-P nor HI-M was the prognostic predictor for overall survival (P=0.078 and 0.063, respectively). 2-Deoxy-2-(F)fluoro-D-glucose-based heterogeneity appears to be a predictive and prognostic factor for patients with HGSC. Parameters of primary tumors have predominant value compared with omental metastatic lesions.

Vehicle Integrated Prognostic Reasoner (VIPR) Final Report

NASA Technical Reports Server (NTRS)

Bharadwaj, Raj; Mylaraswamy, Dinkar; Cornhill, Dennis; Biswas, Gautam; Koutsoukos, Xenofon; Mack, Daniel

2013-01-01

A systems view is necessary to detect, diagnose, predict, and mitigate adverse events during the flight of an aircraft. While most aircraft subsystems look for simple threshold exceedances and report them to a central maintenance computer, the vehicle integrated prognostic reasoner (VIPR) proactively generates evidence and takes an active role in aircraft-level health assessment. Establishing the technical feasibility and a design trade-space for this next-generation vehicle-level reasoning system (VLRS) is the focus of our work.

Prognostic Stratification of Patients With Advanced Oral Cavity Squamous Cell Carcinoma.

PubMed

De Paz, Dante; Kao, Huang-Kai; Huang, Yenlin; Chang, Kai-Ping

2017-08-10

Prognosis of advanced oral squamous cell carcinoma remains a challenge for clinicians despite progress in its diagnosis and treatment over the past decades. In this review, we assessed clinicopathological factors and potential biomarkers along with their prognostic relevance in an attempt to develop optimal treatment strategies for these patients. In addition to several pathologic factors that have been proposed to improve prognostic stratification and treatment planning in the eighth edition of the American Joint Committee staging manual on cancer, we reviewed some other imaging and clinicopathological parameters demonstrated to be closely associated with patient prognosis, along with the biomarkers related to novel target or immune therapy. Evaluation of current literature regarding the prognostic stratification used in contemporary clinicopathological studies and progress in the development of targeted or immune therapy may help these patients benefit from tailored and personalized treatment and obtain better oncological results.

Traditional and emerging molecular markers in neuroblastoma prognosis: the good, the bad and the ugly.

PubMed

Poremba, C; Hero, B; Goertz, H G; Scheel, C; Wai, D; Schaefer, K L; Christiansen, H; Berthold, F; Juergens, H; Boecker, W; Dockhorn-Dworniczak, B

2001-01-01

Neuroblastomas (NB) are a heterogeneous group of childhood tumours with a wide range of likelihood for tumour progression. As traditional parameters do not ensure completely accurate prognostic grouping, new molecular markers are needed for assessing the individual patient's prognosis more precisely. 133 NB of all stages were analysed in blind-trial fashion for telomerase activity (TA), expression of surviving, and MYCN status. These data were correlated with other traditional prognostic indicators and disease outcome. TA is a powerful independent prognostic marker for all stages and is capable of differentiating between good and poor outcome in putative "favourable" clinical or biological subgroups of NB patients. High surviving expression is associated with an adverse outcome, but is more difficult to interprete than TA because survivin expression needs to be accurately quantified to be of predictive value. We propose an extended progression model for NB including emerging prognostic markers, with emphasis on telomerase activity.

Re-irradiation of recurrent gliomas: pooled analysis and validation of an established prognostic score-report of the Radiation Oncology Group (ROG) of the German Cancer Consortium (DKTK).

PubMed

Combs, Stephanie E; Niyazi, Maximilian; Adeberg, Sebastian; Bougatf, Nina; Kaul, David; Fleischmann, Daniel F; Gruen, Arne; Fokas, Emmanouil; Rödel, Claus M; Eckert, Franziska; Paulsen, Frank; Oehlke, Oliver; Grosu, Anca-Ligia; Seidlitz, Annekatrin; Lattermann, Annika; Krause, Mechthild; Baumann, Michael; Guberina, Maja; Stuschke, Martin; Budach, Volker; Belka, Claus; Debus, Jürgen; Kessel, Kerstin A

2018-05-01

The heterogeneity of high-grade glioma recurrences remains an ongoing challenge for the interdisciplinary neurooncology team. Response to re-irradiation (re-RT) is heterogeneous, and survival data depend on prognostic factors such as tumor volume, primary histology, age, the possibility of reresection, or time between primary diagnosis and initial RT and re-RT. In the present pooled analysis, we gathered data from radiooncology centers of the DKTK Consortium and used it to validate the established prognostic score by Combs et al. and its modification by Kessel et al. Data consisted of a large independent, multicenter cohort of 565 high-grade glioma patients treated with re-RT from 1997 to 2016 and a median dose of 36 Gy. Primary RT was between 1986 and 2015 with a median dose of 60 Gy. Median age was 54 years; median follow-up was 7.1 months. Median OS after re-RT was 7.5, 9.5, and 13.8 months for WHO IV, III, and I/II gliomas, respectively. All six prognostic factors were tested for their significance on OS. Aside from the time from primary RT to re-RT (P = 0.074) and the reresection status (P = 0.101), all factors (primary histology, age, KPS, and tumor volume) were significant. Both the original and new score showed a highly significant influence on survival with P < 0.001. Both prognostic scores successfully predict survival after re-RT and can easily be applied in the routine clinical workflow. Now, further prognostic features need to be found to even improve treatment decisions regarding neurooncological interventions for recurrent glioma patients. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Clinico-pathological and biological prognostic variables in squamous cell carcinoma of the vulva.

PubMed

Gadducci, Angiolo; Tana, Roberta; Barsotti, Cecilia; Guerrieri, Maria Elena; Genazzani, Andrea Riccardo

2012-07-01

Several clinical-pathological parameters have been related to survival of patients with invasive squamous cell carcinoma of the vulva, whereas few studies have investigated the ability of biological variables to predict the clinical outcome of these patients. The present paper reviews the literature data on the prognostic relevance of lymph node-related parameters, primary tumor-related parameters, FIGO stage, blood variables, and tissue biological variables. Regarding these latter, the paper takes into account the analysis of DNA content, cell cycle-regulatory proteins, apoptosis-related proteins, epidermal growth factor receptor [EGFR], and proteins that are involved in tumor invasiveness, metastasis and angiogenesis. At present, the lymph node status and FIGO stage according to the new 2009 classification system are the main predictors for vulvar squamous cell carcinoma, whereas biological variables do not have yet a clinical relevance and their role is still investigational. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Proposal for a new risk stratification classification for meningioma based on patient age, WHO tumor grade, size, localization, and karyotype

PubMed Central

Domingues, Patrícia Henriques; Sousa, Pablo; Otero, Álvaro; Gonçalves, Jesus Maria; Ruiz, Laura; de Oliveira, Catarina; Lopes, Maria Celeste; Orfao, Alberto; Tabernero, Maria Dolores

2014-01-01

Background Tumor recurrence remains the major clinical complication of meningiomas, the majority of recurrences occurring among WHO grade I/benign tumors. In the present study, we propose a new scoring system for the prognostic stratification of meningioma patients based on analysis of a large series of meningiomas followed for a median of >5 years. Methods Tumor cytogenetics were systematically investigated by interphase fluorescence in situ hybridization in 302 meningioma samples, and the proposed classification was further validated in an independent series of cases (n = 132) analyzed by high-density (500K) single-nucleotide polymorphism (SNP) arrays. Results Overall, we found an adverse impact on patient relapse-free survival (RFS) for males, presence of brain edema, younger patients (<55 years), tumor size >50 mm, tumor localization at intraventricular and anterior cranial base areas, WHO grade II/III meningiomas, and complex karyotypes; the latter 5 variables showed an independent predictive value in multivariate analysis. Based on these parameters, a prognostic score was established for each individual case, and patients were stratified into 4 risk categories with significantly different (P < .001) outcomes. These included a good prognosis group, consisting of approximately 20% of cases, that showed a RFS of 100% ± 0% at 10 years and a very poor-prognosis group with a RFS rate of 0% ± 0% at 10 years. The prognostic impact of the scoring system proposed here was also retained when WHO grade I cases were considered separately (P < .001). Conclusions Based on this risk-stratification classification, different strategies may be adopted for follow-up, and eventually also for treatment, of meningioma patients at different risks for relapse. PMID:24536048

Prognostic factors and treatment outcomes in 444 patients with mucosal melanoma.

PubMed

Heppt, Markus V; Roesch, Alexander; Weide, Benjamin; Gutzmer, Ralf; Meier, Friedegund; Loquai, Carmen; Kähler, Katharina C; Gesierich, Anja; Meissner, Markus; von Bubnoff, Dagmar; Göppner, Daniela; Schlaak, Max; Pföhler, Claudia; Utikal, Jochen; Heinzerling, Lucie; Cosgarea, Ioana; Engel, Jutta; Eckel, Renate; Martens, Alexander; Mirlach, Laura; Satzger, Imke; Schubert-Fritschle, Gabriele; Tietze, Julia K; Berking, Carola

2017-08-01

Mucosal melanoma (MM) is a rare but diverse cancer entity. Prognostic factors are not well established for Caucasians with MM. We analysed the disease course of 444 patients from 15 German skin cancer centres. Disease progression was determined with the cumulative incidence function. Survival times were estimated with the Kaplan-Meier method. Prognostic parameters were identified with multivariate Cox regression analysis. Common anatomic sites of primary tumours were head and neck (MMHN, 37.2%), female genital tract (MMFG, 30.4%) and anorectal region (MMAN, 21.8%). MMAN patients showed the highest vertical tumour thickness (p = 0.001), had a more advanced nodal status (p = 0.014) and a higher percentage of metastatic disease (p = 0.001) at diagnosis. Mutations of NRAS (13.8%), KIT (8.6%) and BRAF (6.4%) were evenly distributed across all tumour site groups. Local relapses were observed in 32.4% and most commonly occurred in the MMHN group (p = 0.016). Male gender (p = 0.047), advanced tumour stage (p = 0.001), nodal disease (p = 0.001) and incomplete resection status (p = 0.001) were independent risk factors for disease progression. Overall survival (OS) was highest in the MMFG group (p = 0.030) and in patients without ulceration (p = 0.004). Multivariate risk factors for OS were M stage at diagnosis (p = 0.002) and incomplete resection of the primary tumour (p = 0.001). In this large series of MM patients in a European population, anorectal MM was associated with the poorest prognosis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Clinicopathological and prognostic significance of cyclin D1 amplification in patients with breast cancer: a meta-analysis.

PubMed

He, Qi; Wu, Jingxun; Liu, Xin-Li; Ma, Yi-Han; Wu, Xiao-Ting; Wang, Wen-Yi; An, Han-Xiang

2017-01-01

Cyclin D1 plays a critical role in tumorigenesis and the regulation of the G1/S transition in the cell cycle. The relationship between cyclin D1 amplification and clinicopathological parameters in patients with breast cancer remains controversial and its impact on survival outcome is not completely clear. We conducted a meta-analysis to investigate the associations between cyclin D1 gene amplification and certain clinicopathological characteristics and the prognosis in breast cancer. Literature search of PubMed (up to August 3, 2016) was performed. We used Stata 12.0 (Stata Corporation, Texas, US) to analyze the correlations between cyclin D1 amplification and clinicopathological features and the prognostic indicator relapse free survival (RFS) and overall survival (OS) in patients with breast cancer. Publication bias analysis and sensitivity analysis were performed. A total of 9,238 breast cancer patients from 21 studies were included. The pooled odds ratios (ORs) indicated that cyclin D1 amplification was significantly associated with estrogen receptor (ER), progesterone receptor (PR), histological grade and lymph node status, but not associated with human epidermal growth factor receptor-2 (HER2) and tumor size. The combined hazard ratios (HRs) for RFS and OS showed that patients with cyclin D1 amplification displayed a 1.31-fold higher risk of recurrence (HR =1.31, 95% confidence interval (95% CI):1.02-1.60, p<0.01), and a risk of mortality 1.22-fold higher times greater than those without cyclin D1 amplification (HR=1.22, 95% CI:0.99- 1.44, p<0.01), respectively. Our meta-analysis indicated that cyclin D1 amplification is significantly associated with established clinicopathological variables and can be used as a poor prognostic indicator for patients with breast cancer.

Heat shock protein 27 as a prognostic and predictive biomarker in pancreatic ductal adenocarcinoma

PubMed Central

Schäfer, Claus; Seeliger, Hendrik; Bader, Dominik C; Assmann, Gerald; Buchner, Denise; Guo, Yang; Ziesch, Andreas; Palagyi, Andreas; Ochs, Stephanie; Laubender, Rüdiger P; Jung, Andreas; De Toni, Enrico N; Kirchner, Thomas; Göke, Burkhard; Bruns, Christiane; Gallmeier, Eike

2012-01-01

Abstract A role of heat shock protein 27 (HSP27) as a potential biomarker has been reported in various tumour entities, but comprehensive studies in pancreatic cancer are lacking. Applying tissue microarray (TMA) analysis, we correlated HSP27 protein expression status with clinicopathologic parameters in pancreatic ductal adenocarcinoma specimens from 86 patients. Complementary, we established HSP27 overexpression and RNA-interference models to assess the impact of HSP27 on chemo- and radiosensitivity directly in pancreatic cancer cells. In the TMA study, HSP27 expression was found in 49% of tumour samples. Applying univariate analyses, a significant correlation was found between HSP27 expression and survival. In the multivariate Cox-regression model, HSP27 expression emerged as an independent prognostic factor. HSP27 expression also correlated inversely with nuclear p53 accumulation, indicating either protein interactions between HSP27 and p53 or TP53 mutation-dependent HSP27-regulation in pancreatic cancer. In the sensitivity studies, HSP27 overexpression rendered HSP27 low-expressing PL5 pancreatic cancer cells more susceptible towards treatment with gemcitabine. Vice versa, HSP27 protein depletion in HSP27 high-expressing AsPC-1 cells caused increased gemcitabine resistance. Importantly, HSP27 expression was inducible in pancreatic cancer cell lines as well as primary cells. Taken together, our study suggests a role for HSP27 as a prognostic and predictive marker in pancreatic cancer. Assessment of HSP27 expression could thus facilitate the identification of specific patient subpopulations that might benefit from individualized treatment options. Additional studies need to clarify whether modulation of HSP27 expression could represent an attractive concept to support the incorporation of hyperthermia in clinical treatment protocols for pancreatic cancer. PMID:22004109

Functional parameters but not heart rate variability correlate with long-term outcomes in St-elevation myocardial infarction patients treated by primary angioplasty.

PubMed

Compostella, Leonida; Lakusic, Nenad; Russo, Nicola; Setzu, Tiziana; Compostella, Caterina; Vettore, Elia; Isabella, Giambattista; Tarantini, Giuseppe; Iliceto, Sabino; Bellotto, Fabio

2016-12-01

Depressed heart rate variability (HRV) is usually considered a negative long-term prognostic factor after acute myocardial infarction. Anyway, most of the supporting research was conducted before the era of immediate reperfusion by percutaneous coronary intervention (PCI). Main aim of this study was to evaluate if HRV still retains prognostic significance in our era of immediate PCI. Two weeks after STEMI treated by primary PCI, time-domain HRV was assessed from 24-h Holter recordings in 186 patients: markedly depressed HRV (SDNN <70ms or <50ms) was present in 16% and in 5% of cases, respectively; patients with left ventricle ejection fraction (LVEF) <40% presented more often SDNN values in the lowest quartile. Physical performance was also assessed, by 6-minute walk tests (6MWT) and by cardiopulmonary exercise test (CPET). After >2years from infarction, occurrence of major clinical events (MCE) was investigated. Cases with or without MCE did not differ by initial HRV parameters; Kaplan-Meier events-free survival curves were similar between patients with lowest quartile SDNN and the remaining ones (χ 2 0.981, p=0.322). By the contrary, events-free survival was worse if patients walked shorter distances at 6MWT (χ 2 6.435, p=0.011), developed poorer ventilatory efficiency at CPET (χ 2 10.060, p=0.002), or presented LVEF <40% (χ 2 7.085, p=0.008). In primary-PCI STEMI patients, markedly abnormal HRV was found in a small percentage of cases. HRV seems to have lost its prognostic significance, while parameters indicating LV function (LVEF and physical performance) could allow better prognostication in primary-PCI STEMI patients. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The Preoperative Composite Physiologic Index May Predict Mortality in Lung Cancer Patients with Combined Pulmonary Fibrosis and Emphysema.

PubMed

Ueno, Fumika; Kitaguchi, Yoshiaki; Shiina, Takayuki; Asaka, Shiho; Miura, Kentaro; Yasuo, Masanori; Wada, Yosuke; Yoshizawa, Akihiko; Hanaoka, Masayuki

2017-01-01

It remains unclear whether the preoperative pulmonary function parameters and prognostic indices that are indicative of nutritional and immunological status are associated with prognosis in lung cancer patients with combined pulmonary fibrosis and emphysema (CPFE) who have undergone surgery. The aim of this study is to identify prognostic determinants in these patients. The medical records of all patients with lung cancer associated with CPFE who had undergone surgery at Shinshu University Hospital were retrospectively reviewed to obtain clinical data, including the results of preoperative pulmonary function tests and laboratory examinations, chest high-resolution computed tomography (HRCT), and survival. Univariate Cox proportional hazards regression analysis showed that a high pathological stage of the lung cancer, a higher preoperative serum carcinoembryonic antigen level, and a higher preoperative composite physiologic index (CPI) were associated with a high risk of death. Multivariate analysis showed that a high pathological stage of the lung cancer (HR: 1.579; p = 0.0305) and a higher preoperative CPI (HR: 1.034; p = 0.0174) were independently associated with a high risk of death. In contrast, the severity of fibrosis or emphysema on chest HRCT, the individual pulmonary function parameters, the prognostic nutritional index, the neutrophil-to-lymphocyte ratio, and the platelet-to-lymphocyte ratio were not associated with prognosis. In the Kaplan-Meier analysis, the log-rank test showed significant differences in survival between the high-CPI and the low-CPI group (p = 0.0234). The preoperative CPI may predict mortality and provide more powerful prognostic information than individual pulmonary function parameters in lung cancer patients with CPFE who have undergone surgery. © 2017 S. Karger AG, Basel.

Histomorphologic parameters and CXCR4 mRNA and protein expression in sentinel node melanoma metastasis are correlated to clinical outcome.

PubMed

Franco, Renato; Cantile, Monica; Scala, Stefania; Catalano, Elisabetta; Cerrone, Margherita; Scognamiglio, Giosuè; Pinto, Antonio; Chiofalo, Maria Grazia; Caracò, Corrado; Anniciello, Anna Maria; Abbruzzese, Alberto; Caraglia, Michele; Botti, Gerardo

2010-03-15

Sentinel lymph node (SLN) biopsy is an important independent prognostic factor for invasive cutaneuos melanoma, although its role is strongly debated. In clinical practice SLN leads to complete lymph node dissection of basin draining melanoma site. However only 7-30% of positive sentinel node patients present additional non SLN metastasis. Melanoma cells diffusion through SLN and extranodal spreading depends upon biological features, such as cell chemokine receptors and adhesion molecules. CXCR4 has been proposed in melanoma patients as prognostic marker. Therefore we have analyzed both histopathological parameters and CXCR4 expression in melanoma infiltrate of SLN, in order to evaluate its potential prognostic role. Micrometastases were detected in 23 cases (48.93%); metastases >2 mm in 23 cases (48.93%) and isolated metastatic cells in one case (2.01%). High CXCR4 expression was observed in 21 nodal metastases. Node metastases in complete dissection were associated to >10% relative tumor area (RTA) in all lymph nodes (p = 0.006). Extranodal invasion (p = 0.006) and >2 mm centripetal metastasis thickness (p = 0.01), while shorter Disease Free Survival (DFS) was significantly associated to high CXCR4 expression (p = 0.02). Forty-seven positive lymph node metastases were collected and analysed for both histopathological parameters and CXCR4 expression. More than 10% RTA in SLN, extranodal invasion and centripetal metastasis thickness all predict additional lymph node metastases in melanoma site draining basins. Moreover, high CXCR4 expression is correlated to shorter DFS and could be used as a prognostic marker in order to stratify melanoma patients at higher progression risk.

A Novel Independent Survival Predictor in Pulmonary Embolism: Prognostic Nutritional Index.

PubMed

Hayıroğlu, Mert İlker; Keskin, Muhammed; Keskin, Taha; Uzun, Ahmet Okan; Altay, Servet; Kaya, Adnan; Öz, Ahmet; Çinier, Göksel; Güvenç, Tolga Sinan; Kozan, Ömer

2018-05-01

The prognostic impact of nutritional status in patients with pulmonary embolism (PE) is poorly understood. A well-accepted nutritional status parameter, prognostic nutritional index (PNI), which was first demonstrated to be valuable in patients with cancer and gastrointestinal surgery, was introduced to patients with PE. Our aim was to evaluate the predictive value of PNI in outcomes of patients with PE. We evaluated the in-hospital and long-term (53.8 ± 5.4 months) prognostic impact of PNI on 251 patients with PE. During a median follow-up of 53.8 ± 5.4 months, 27 (11.6%) patients died in hospital course and 31 (13.4%) died in out-of-hospital course. The patients with lower PNI had significantly higher in-hospital and long-term mortality. The Cox proportional hazard analyses showed that PNI was associated with an increased risk of all-cause death for both unadjusted model and adjusted for all covariates. Our study demonstrated that PNI, calculated based on serum albumin level and lymphocyte count, is an independent prognostic factor for mortality in patients with PE.

Intrinsic Molecular Subtypes of Glioma Are Prognostic and Predict Benefit From Adjuvant Procarbazine, Lomustine, and Vincristine Chemotherapy in Combination With Other Prognostic Factors in Anaplastic Oligodendroglial Brain Tumors: A Report From EORTC Study 26951

PubMed Central

Erdem-Eraslan, Lale; Gravendeel, Lonneke A.; de Rooi, Johan; Eilers, Paul H.C.; Idbaih, Ahmed; Spliet, Wim G.M.; den Dunnen, Wilfred F.A.; Teepen, Johannes L.; Wesseling, Pieter; Sillevis Smitt, Peter A.E.; Kros, Johan M.; Gorlia, Thierry; van den Bent, Martin J.; French, Pim J.

2013-01-01

Purpose Intrinsic glioma subtypes (IGSs) are molecularly similar tumors that can be identified based on unsupervised gene expression analysis. Here, we have evaluated the clinical relevance of these subtypes within European Organisation for Research and Treatment of Cancer (EORTC) 26951, a randomized phase III clinical trial investigating adjuvant procarbazine, lomustine, and vincristine (PCV) chemotherapy in anaplastic oligodendroglial tumors. Our study includes gene expression profiles of formalin-fixed, paraffin-embedded (FFPE) clinical trial samples. Patients and Methods Gene expression profiling was performed in 140 samples, 47 fresh frozen samples and 93 FFPE samples, on HU133_Plus_2.0 and HuEx_1.0_st arrays, respectively. Results All previously identified six IGSs are present in EORTC 26951. This confirms that different molecular subtypes are present within a well-defined histologic subtype. Intrinsic subtypes are highly prognostic for overall survival (OS) and progression-free survival (PFS). They are prognostic for PFS independent of clinical (age, performance status, and tumor location), molecular (1p/19q loss of heterozygosity [LOH], IDH1 mutation, and MGMT methylation), and histologic parameters. Combining known molecular (1p/19q LOH, IDH1) prognostic parameters with intrinsic subtypes improves outcome prediction (proportion of explained variation, 30% v 23% for each individual group of factors). Specific genetic changes (IDH1, 1p/19q LOH, and EGFR amplification) segregate into different subtypes. We identified one subtype, IGS-9 (characterized by a high percentage of 1p/19q LOH and IDH1 mutations), that especially benefits from PCV chemotherapy. Median OS in this subtype was 5.5 years after radiotherapy (RT) alone versus 12.8 years after RT/PCV (P = .0349; hazard ratio, 2.18; 95% CI, 1.06 to 4.50). Conclusion Intrinsic subtypes are highly prognostic in EORTC 26951 and improve outcome prediction when combined with other prognostic factors. Tumors assigned to IGS-9 benefit from adjuvant PCV. PMID:23269986

Chromosome aberrations detected by conventional karyotyping using novel mitogens in chronic lymphocytic leukemia with "normal" FISH: correlations with clinicobiologic parameters.

PubMed

Rigolin, Gian Matteo; Cibien, Francesca; Martinelli, Sara; Formigaro, Luca; Rizzotto, Lara; Tammiso, Elisa; Saccenti, Elena; Bardi, Antonella; Cavazzini, Francesco; Ciccone, Maria; Nichele, Ilaria; Pizzolo, Giovanni; Zaja, Francesco; Fanin, Renato; Galieni, Piero; Dalsass, Alessia; Mestichelli, Francesca; Testa, Nicoletta; Negrini, Massimo; Cuneo, Antonio

2012-03-08

It is unclear whether karyotype aberrations that occur in regions uncovered by the standard fluorescence in situ hybridization (FISH) panel have prognostic relevance in chronic lymphocytic leukemia (CLL). We evaluated the significance of karyotypic aberrations in a learning cohort (LC; n = 64) and a validation cohort (VC; n = 84) of patients with chronic lymphocytic leukemia with "normal" FISH. An abnormal karyotype was found in 21.5% and 35.7% of cases in the LC and VC, respectively, and was associated with a lower immunophenotypic score (P = .030 in the LC, P = .035 in the VC), advanced stage (P = .040 in the VC), and need for treatment (P = .002 in the LC, P = < .0001 in the VC). The abnormal karyotype correlated with shorter time to first treatment and shorter survival in both the LC and the VC, representing the strongest prognostic parameter. In patients with chronic lymphocytic leukemia with normal FISH, karyotypic aberrations by conventional cytogenetics with novel mitogens identify a subset of cases with adverse prognostic features.

FCG (FLIPI, Charlson comorbidity index, and histological grade) score is superior to FLIPI in advanced follicular lymphoma.

PubMed

Mihaljevic, Biljana; Jelicic, Jelena; Andjelic, Bosko; Antic, Darko; Markovic, Olivera; Petkovic, Ivan; Jovanovic, Maja Perunicic; Trajkovic, Goran; Bila, Jelena; Djurasinovic, Vladislava; Sretenovic, Aleksandra; Vukovic, Vojin; Smiljanic, Mihailo; Balint, Milena Todorovic

2016-12-01

The Follicular Lymphoma International Prognostic Index (FLIPI) is widely used in the identification of risk groups among follicular lymphoma (FL) patients. The aim of the present study was to evaluate the prognostic value of FLIPI combined with the Charlson comorbidity index (CCI) and histological grade of lymphoma. 224 newly diagnosed FL patients (median age 56 years) treated with immunochemotherapy were retrospectively analysed. Low FLIPI had 21.0 % of patients, intermediate 28.1 % and high 46.9 %. 50.9 % of patients had no comorbidities. Only 7.1 % of patients had a high CCI score (≥2), while 25.9 % of patients were histological grade 3. Parameters that influenced overall survival were evaluated using Cox regression analysis, in which CCI, FLIPI and histological grade (p < 0.05) retained prognostic significance. By combining these parameters, we have developed the FCG score, which incorporates FLIPI, CCI, and histological grade. This score defines three risk categories (low: 41.5 %; intermediate: 37.5 %; high: 13.4 %), associated with significantly different survival (p < 0.0001); this consequently improves discriminative power by 9.1 % compared to FLIPI. FCG score represents a possible new prognostic index, highlighting the role of the patient's clinical state and the histological characteristics of disease, as indicated by comorbidity index and histological grade of lymphoma.

Electromechanical actuators affected by multiple failures: Prognostic method based on spectral analysis techniques

NASA Astrophysics Data System (ADS)

Belmonte, D.; Vedova, M. D. L. Dalla; Ferro, C.; Maggiore, P.

2017-06-01

The proposal of prognostic algorithms able to identify precursors of incipient failures of primary flight command electromechanical actuators (EMA) is beneficial for the anticipation of the incoming failure: an early and correct interpretation of the failure degradation pattern, in fact, can trig an early alert of the maintenance crew, who can properly schedule the servomechanism replacement. An innovative prognostic model-based approach, able to recognize the EMA progressive degradations before his anomalous behaviors become critical, is proposed: the Fault Detection and Identification (FDI) of the considered incipient failures is performed analyzing proper system operational parameters, able to put in evidence the corresponding degradation path, by means of a numerical algorithm based on spectral analysis techniques. Subsequently, these operational parameters will be correlated with the actual EMA health condition by means of failure maps created by a reference monitoring model-based algorithm. In this work, the proposed method has been tested in case of EMA affected by combined progressive failures: in particular, partial stator single phase turn to turn short-circuit and rotor static eccentricity are considered. In order to evaluate the prognostic method, a numerical test-bench has been conceived. Results show that the method exhibit adequate robustness and a high degree of confidence in the ability to early identify an eventual malfunctioning, minimizing the risk of fake alarms or unannounced failures.

Tumour functional sphericity from PET images: prognostic value in NSCLC and impact of delineation method.

PubMed

Hatt, Mathieu; Laurent, Baptiste; Fayad, Hadi; Jaouen, Vincent; Visvikis, Dimitris; Le Rest, Catherine Cheze

2018-04-01

Sphericity has been proposed as a parameter for characterizing PET tumour volumes, with complementary prognostic value with respect to SUV and volume in both head and neck cancer and lung cancer. The objective of the present study was to investigate its dependency on tumour delineation and the resulting impact on its prognostic value. Five segmentation methods were considered: two thresholds (40% and 50% of SUV max ), ant colony optimization, fuzzy locally adaptive Bayesian (FLAB), and gradient-aided region-based active contour. The accuracy of each method in extracting sphericity was evaluated using a dataset of 176 simulated, phantom and clinical PET images of tumours with associated ground truth. The prognostic value of sphericity and its complementary value with respect to volume for each segmentation method was evaluated in a cohort of 87 patients with stage II/III lung cancer. Volume and associated sphericity values were dependent on the segmentation method. The correlation between segmentation accuracy and sphericity error was moderate (|ρ| from 0.24 to 0.57). The accuracy in measuring sphericity was not dependent on volume (|ρ| < 0.4). In the patients with lung cancer, sphericity had prognostic value, although lower than that of volume, except for that derived using FLAB for which when combined with volume showed a small improvement over volume alone (hazard ratio 2.67, compared with 2.5). Substantial differences in patient prognosis stratification were observed depending on the segmentation method used. Tumour functional sphericity was found to be dependent on the segmentation method, although the accuracy in retrieving the true sphericity was not dependent on tumour volume. In addition, even accurate segmentation can lead to an inaccurate sphericity value, and vice versa. Sphericity had similar or lower prognostic value than volume alone in the patients with lung cancer, except when determined using the FLAB method for which there was a small improvement in stratification when the parameters were combined.

Molecular markers to complement sentinel node status in predicting survival in patients with high-risk locally invasive melanoma.

PubMed

Rowe, Casey J; Tang, Fiona; Hughes, Maria Celia B; Rodero, Mathieu P; Malt, Maryrose; Lambie, Duncan; Barbour, Andrew; Hayward, Nicholas K; Smithers, B Mark; Green, Adele C; Khosrotehrani, Kiarash

2016-08-01

Sentinel lymph node status is a major prognostic marker in locally invasive cutaneous melanoma. However, this procedure is not always feasible, requires advanced logistics and carries rare but significant morbidity. Previous studies have linked markers of tumour biology to patient survival. In this study, we aimed to combine the predictive value of established biomarkers in addition to clinical parameters as indicators of survival in addition to or instead of sentinel node biopsy in a cohort of high-risk melanoma patients. Patients with locally invasive melanomas undergoing sentinel lymph node biopsy were ascertained and prospectively followed. Information on mortality was validated through the National Death Index. Immunohistochemistry was used to analyse proteins previously reported to be associated with melanoma survival, namely Ki67, p16 and CD163. Evaluation and multivariate analyses according to REMARK criteria were used to generate models to predict disease-free and melanoma-specific survival. A total of 189 patients with available archival material of their primary tumour were analysed. Our study sample was representative of the entire cohort (N = 559). Average Breslow thickness was 2.5 mm. Thirty-two (17%) patients in the study sample died from melanoma during the follow-up period. A prognostic score was developed and was strongly predictive of survival, independent of sentinel node status. The score allowed classification of risk of melanoma death in sentinel node-negative patients. Combining clinicopathological factors and established biomarkers allows prediction of outcome in locally invasive melanoma and might be implemented in addition to or in cases when sentinel node biopsy cannot be performed. © 2016 UICC.

An Overview of Systematic Reviews on Prognostic Factors in Neck Pain: Results from the International Collaboration on Neck Pain (ICON) Project

PubMed Central

Walton, David M; Carroll, Linda J; Kasch, Helge; Sterling, Michele; Verhagen, Arianne P; MacDermid, Joy C; Gross, Anita; Santaguida, P. Lina; Carlesso, Lisa

2013-01-01

Given the challenges of chronic musculoskeletal pain and disability, establishing a clear prognosis in the acute stage has become increasingly recognized as a valuable approach to mitigate chronic problems. Neck pain represents a condition that is common, potentially disabling, and has a high rate of transition to chronic or persistent problems. As a field of research, prognosis in neck pain has stimulated several empirical primary research papers, and a number of systematic reviews. As part of the International Consensus on Neck (ICON) project, we sought to establish the general state of knowledge in the area through a structured, systematic review of systematic reviews (overview). An exhaustive search strategy was created and employed to identify the 13 systematic reviews (SRs) that served as the primary data sources for this overview. A decision algorithm for data synthesis, which incorporated currency of the SR, risk of bias assessment of the SRs using AMSTAR scoring and consistency of findings across SRs, determined the level of confidence in the risk profile of 133 different variables. The results provide high confidence that baseline neck pain intensity and baseline disability have a strong association with outcome, while angular deformities of the neck and parameters of the initiating trauma have no effect on outcome. A vast number of predictors provide low or very low confidence or inconclusive results, suggesting there is still much work to be done in this field. Despite the presence of multiple SR and this overview, there is insufficient evidence to make firm conclusions on many potential prognostic variables. This study demonstrates the challenges in conducting overviews on prognosis where clear synthesis critieria and a lack of specifics of primary data in SR are barriers. PMID:24115971

Next-generation prognostic assessment for diffuse large B-cell lymphoma

PubMed Central

Staton, Ashley D; Kof, Jean L; Chen, Qiushi; Ayer, Turgay; Flowers, Christopher R

2015-01-01

Current standard of care therapy for diffuse large B-cell lymphoma (DLBCL) cures a majority of patients with additional benefit in salvage therapy and autologous stem cell transplant for patients who relapse. The next generation of prognostic models for DLBCL aims to more accurately stratify patients for novel therapies and risk-adapted treatment strategies. This review discusses the significance of host genetic and tumor genomic alterations seen in DLBCL, clinical and epidemiologic factors, and how each can be integrated into risk stratification algorithms. In the future, treatment prediction and prognostic model development and subsequent validation will require data from a large number of DLBCL patients to establish sufficient statistical power to correctly predict outcome. Novel modeling approaches can augment these efforts. PMID:26289217

Next-generation prognostic assessment for diffuse large B-cell lymphoma.

PubMed

Staton, Ashley D; Koff, Jean L; Chen, Qiushi; Ayer, Turgay; Flowers, Christopher R

2015-01-01

Current standard of care therapy for diffuse large B-cell lymphoma (DLBCL) cures a majority of patients with additional benefit in salvage therapy and autologous stem cell transplant for patients who relapse. The next generation of prognostic models for DLBCL aims to more accurately stratify patients for novel therapies and risk-adapted treatment strategies. This review discusses the significance of host genetic and tumor genomic alterations seen in DLBCL, clinical and epidemiologic factors, and how each can be integrated into risk stratification algorithms. In the future, treatment prediction and prognostic model development and subsequent validation will require data from a large number of DLBCL patients to establish sufficient statistical power to correctly predict outcome. Novel modeling approaches can augment these efforts.

Refining prognosis in lung cancer: A report on the quality and relevance of clinical prognostic tools

PubMed Central

Mahar, Alyson L.; Compton, Carolyn; McShane, Lisa M.; Halabi, Susan; Asamura, Hisao; Rami-Porta, Ramon; Groome, Patti A.

2015-01-01

Introduction Accurate, individualized prognostication for lung cancer patients requires the integration of standard patient and pathologic factors, biologic, genetic, and other molecular characteristics of the tumor. Clinical prognostic tools aim to aggregate information on an individual patient to predict disease outcomes such as overall survival, but little is known about their clinical utility and accuracy in lung cancer. Methods A systematic search of the scientific literature for clinical prognostic tools in lung cancer published Jan 1, 1996-Jan 27, 2015 was performed. In addition, web-based resources were searched. A priori criteria determined by the Molecular Modellers Working Group of the American Joint Committee on Cancer were used to investigate the quality and usefulness of tools. Criteria included clinical presentation, model development approaches, validation strategies, and performance metrics. Results Thirty-two prognostic tools were identified. Patients with metastases were the most frequently considered population in non-small cell lung cancer. All tools for small cell lung cancer covered that entire patient population. Included prognostic factors varied considerably across tools. Internal validity was not formally evaluated for most tools and only eleven were evaluated for external validity. Two key considerations were highlighted for tool development: identification of an explicit purpose related to a relevant clinical population and clear decision-points, and prioritized inclusion of established prognostic factors over emerging factors. Conclusions Prognostic tools will contribute more meaningfully to the practice of personalized medicine if better study design and analysis approaches are used in their development and validation. PMID:26313682

Left Ventricular Function Parameters in a Hispanic Population: Comparison of Planar & Tomographic Radionuclide Ventriculography (MUGA).

PubMed

Martin, Ralph J; Santiago, Bartolo

2015-09-01

Left ventricular (LV) function parameters have major diagnostic and prognostic importance in heart disease. Measurement of ventricular function with tomographic (SPECT) radionuclide ventriculography (MUGA) decreases camera time, improves contrast resolution, accuracy of interpretation and the overall reliability of the study as compared to planar MUGA. The relationship between these techniques is well established particularly with LV ejection fraction (LVEF), while there is limited data comparing the diastolic function parameters. Our goal was to validate the LV function parameters in our Hispanic population. Studies from 44 patients, available from 2009-2010, were retrospectively evaluated. LVEF showed a good correlation between the techniques (r=0.94) with an average difference of 3.8%. In terms of categorizing the results as normal or abnormal, this remained unchanged in 95% of the cases (p=0.035). For the peak filling rate, there was a moderate correlation between the techniques (r=0.71), whereas the diagnosis remained unchanged in 89% of cases (p=0.0004). Time to peak filling values only demonstrated a weak correlation (r=0.22). Nevertheless, the diagnosis remained the same in 68% of the cases (p=0.089). Systolic function results in our study were well below the 7-10% difference reported in the literature. Only a weak to moderate correlation was observed with the diastolic function parameters. Comparison with echocardiogram (not available) may be of benefit to evaluate which of these techniques results in more accurate diastolic function parameters.

Validation and Development of a Modified Breast Graded Prognostic Assessment As a Tool for Survival in Patients With Breast Cancer and Brain Metastases.

PubMed

Subbiah, Ishwaria M; Lei, Xiudong; Weinberg, Jeffrey S; Sulman, Erik P; Chavez-MacGregor, Mariana; Tripathy, Debu; Gupta, Rohan; Varma, Ankur; Chouhan, Jay; Guevarra, Richard P; Valero, Vicente; Gilbert, Mark R; Gonzalez-Angulo, Ana M

2015-07-10

Several indices have been developed to predict overall survival (OS) in patients with breast cancer with brain metastases, including the breast graded prognostic assessment (breast-GPA), comprising age, tumor subtype, and Karnofsky performance score. However, number of brain metastases-a highly relevant clinical variable-is less often incorporated into the final model. We sought to validate the existing breast-GPA in an independent larger cohort and refine it integrating number of brain metastases. Data were retrospectively gathered from a prospectively maintained institutional database. Patients with newly diagnosed brain metastases from 1996 to 2013 were identified. After validating the breast-GPA, multivariable Cox regression and recursive partitioning analysis led to the development of the modified breast-GPA. The performances of the breast-GPA and modified breast-GPA were compared using the concordance index. In our cohort of 1,552 patients, the breast-GPA was validated as a prognostic tool for OS (P < .001). In multivariable analysis of the breast-GPA and number of brain metastases (> three v ≤ three), both were independent predictors of OS. We therefore developed the modified breast-GPA integrating a fourth clinical parameter. Recursive partitioning analysis reinforced the prognostic significance of these four factors. Concordance indices were 0.78 (95% CI, 0.77 to 0.80) and 0.84 (95% CI, 0.83 to 0.85) for the breast-GPA and modified breast-GPA, respectively (P < .001). The modified breast-GPA incorporates four simple clinical parameters of high prognostic significance. This index has an immediate role in the clinic as a formative part of the clinician's discussion of prognosis and direction of care and as a potential patient selection tool for clinical trials. © 2015 by American Society of Clinical Oncology.

Measuring the apparent diffusion coefficient in primary rectal tumors: is there a benefit in performing histogram analyses?

PubMed

van Heeswijk, Miriam M; Lambregts, Doenja M J; Maas, Monique; Lahaye, Max J; Ayas, Z; Slenter, Jos M G M; Beets, Geerard L; Bakers, Frans C H; Beets-Tan, Regina G H

2017-06-01

The apparent diffusion coefficient (ADC) is a potential prognostic imaging marker in rectal cancer. Typically, mean ADC values are used, derived from precise manual whole-volume tumor delineations by experts. The aim was first to explore whether non-precise circular delineation combined with histogram analysis can be a less cumbersome alternative to acquire similar ADC measurements and second to explore whether histogram analyses provide additional prognostic information. Thirty-seven patients who underwent a primary staging MRI including diffusion-weighted imaging (DWI; b0, 25, 50, 100, 500, 1000; 1.5 T) were included. Volumes-of-interest (VOIs) were drawn on b1000-DWI: (a) precise delineation, manually tracing tumor boundaries (2 expert readers), and (b) non-precise delineation, drawing circular VOIs with a wide margin around the tumor (2 non-experts). Mean ADC and histogram metrics (mean, min, max, median, SD, skewness, kurtosis, 5th-95th percentiles) were derived from the VOIs and delineation time was recorded. Measurements were compared between the two methods and correlated with prognostic outcome parameters. Median delineation time reduced from 47-165 s (precise) to 21-43 s (non-precise). The 45th percentile of the non-precise delineation showed the best correlation with the mean ADC from the precise delineation as the reference standard (ICC 0.71-0.75). None of the mean ADC or histogram parameters showed significant prognostic value; only the total tumor volume (VOI) was significantly larger in patients with positive clinical N stage and mesorectal fascia involvement. When performing non-precise tumor delineation, histogram analysis (in specific 45th ADC percentile) may be used as an alternative to obtain similar ADC values as with precise whole tumor delineation. Histogram analyses are not beneficial to obtain additional prognostic information.

Hashimoto's thyroiditis predicts outcome in intrathyroidal papillary thyroid cancer.

PubMed

Marotta, Vincenzo; Sciammarella, Concetta; Chiofalo, Maria Grazia; Gambardella, Claudio; Bellevicine, Claudio; Grasso, Marica; Conzo, Giovanni; Docimo, Giovanni; Botti, Gerardo; Losito, Simona; Troncone, Giancarlo; De Palma, Maurizio; Giacomelli, Laura; Pezzullo, Luciano; Colao, Annamaria; Faggiano, Antongiulio

2017-09-01

Hashimoto's thyroiditis (HT) seems to have favourable prognostic impact on papillary thyroid cancer (PTC), but data were obtained analysing all disease stages. Given that HT-related microenvironment involves solely the thyroid, we aimed to assess the relationship between HT, as detected through pathological assessment, and outcome in intrathyroidal PTC. This was a multicentre, retrospective, observational study including 301 PTC with no evidence of extrathyroidal disease. Primary study endpoint was the rate of clinical remission. Auxiliary endpoint was recurrence-free survival (RFS). HT was detected in 42.5% of the cohort and was associated to female gender, smaller tumour size, lower rate of aggressive PTC variants and less frequent post-surgery radio-iodine administration. HT showed relationship with significantly higher rate of clinical remission ( P  < 0.001, OR 4, 95% CI 1.78-8.94). PTCs with concomitant HT had significantly longer RFS, as compared with non-HT tumours ( P  = 0.004). After adjustment for other parameters affecting disease outcome at univariate analysis (age at diagnosis, histology, tumour size and multifocality), prognostic effect of HT remained significant ( P  = 0.006, OR 3.28, 95% CI 1.39-7.72). To verify whether HT could optimise the identification of PTCs with unfavourable outcome, we assessed the accuracy of 'non-HT status' as negative prognostic marker, demonstrating poor capability of identifying patients not maintaining clinical remission until final follow-up (probability of no clinical remission in PTCs without HT: 21.05%, 95% CI 15.20-27.93). In conclusion, our data show that HT represents an independent prognostic parameter in intrathyroidal PTC, but cannot improve prognostic specificity. © 2017 Society for Endocrinology.

Machine Learning Approach to Extract Diagnostic and Prognostic Thresholds: Application in Prognosis of Cardiovascular Mortality

PubMed Central

Mena, Luis J.; Orozco, Eber E.; Felix, Vanessa G.; Ostos, Rodolfo; Melgarejo, Jesus; Maestre, Gladys E.

2012-01-01

Machine learning has become a powerful tool for analysing medical domains, assessing the importance of clinical parameters, and extracting medical knowledge for outcomes research. In this paper, we present a machine learning method for extracting diagnostic and prognostic thresholds, based on a symbolic classification algorithm called REMED. We evaluated the performance of our method by determining new prognostic thresholds for well-known and potential cardiovascular risk factors that are used to support medical decisions in the prognosis of fatal cardiovascular diseases. Our approach predicted 36% of cardiovascular deaths with 80% specificity and 75% general accuracy. The new method provides an innovative approach that might be useful to support decisions about medical diagnoses and prognoses. PMID:22924062

Prognostic model based on nailfold capillaroscopy for identifying Raynaud's phenomenon patients at high risk for the development of a scleroderma spectrum disorder: PRINCE (prognostic index for nailfold capillaroscopic examination).

PubMed

Ingegnoli, Francesca; Boracchi, Patrizia; Gualtierotti, Roberta; Lubatti, Chiara; Meani, Laura; Zahalkova, Lenka; Zeni, Silvana; Fantini, Flavio

2008-07-01

To construct a prognostic index based on nailfold capillaroscopic examinations that is capable of predicting the 5-year transition from isolated Raynaud's phenomenon (RP) to RP secondary to scleroderma spectrum disorders (SSDs). The study involved 104 consecutive adult patients with a clinical history of isolated RP, and the index was externally validated in another cohort of 100 patients with the same characteristics. Both groups were followed up for 1-8 years. Six variables were examined because of their potential prognostic relevance (branching, enlarged and giant loops, capillary disorganization, microhemorrhages, and the number of capillaries). The only factors that played a significant prognostic role were the presence of giant loops (hazard ratio [HR] 2.64, P = 0.008) and microhemorrhages (HR 2.33, P = 0.01), and the number of capillaries (analyzed as a continuous variable). The adjusted prognostic role of these factors was evaluated by means of multivariate regression analysis, and the results were used to construct an algorithm-based prognostic index. The model was internally and externally validated. Our prognostic capillaroscopic index identifies RP patients in whom the risk of developing SSDs is high. This model is a weighted combination of different capillaroscopy parameters that allows physicians to stratify RP patients easily, using a relatively simple diagram to deduce the prognosis. Our results suggest that this index could be used in clinical practice, and its further inclusion in prospective studies will undoubtedly help in exploring its potential in predicting treatment response.

The use of health status questionnaires in the management of chronic obstructive pulmonary disease patients in clinical practice.

PubMed

van der Molen, Thys; Diamant, Zuzana; Kocks, Jan Willem H; Tsiligianni, Ioanna G

2014-08-01

Current guidelines recommend chronic obstructive pulmonary disease (COPD) management based on symptoms or health status assessment and lung function parameters. However, COPD is a complex and heterogeneous disease that needs an individualized approach for proper disease management. A structured consultation including health status assessment tools, such as the Clinical COPD Questionnaire and the COPD Assessment Test should improve the quality of the consultation, providing more information than symptoms alone. Both questionnaires are designed to provide the clinician information enabling a more personalized disease approach and subsequent management. Although both Clinical COPD Questionnaire and COPD Assessment Test have good discriminate properties, their use as prognostic markers of severity and their ability to modify disease management has not yet been fully established. New studies are needed to further determine their value on several disease outcomes.

Introducing a novel highly prognostic grading scheme based on tumour budding and cell nest size for squamous cell carcinoma of the uterine cervix.

PubMed

Jesinghaus, Moritz; Strehl, Johanna; Boxberg, Melanie; Brühl, Frido; Wenzel, Adrian; Konukiewitz, Björn; Schlitter, Anna M; Steiger, Katja; Warth, Arne; Schnelzer, Andreas; Kiechle, Marion; Beckmann, Matthias W; Noske, Aurelia; Hartmann, Arndt; Mehlhorn, Grit; Koch, Martin C; Weichert, Wilko

2018-04-01

A novel histopathological grading system based on tumour budding and cell nest size has recently been shown to outperform conventional (WHO-based) grading algorithms in several tumour entities such as lung, oral, and oesophageal squamous cell carcinoma (SCC) in terms of prognostic patient stratification. Here, we tested the prognostic value of this innovative grading approach in two completely independent cohorts of SCC of the uterine cervix. To improve morphology-based grading, we investigated tumour budding activity and cell nest size as well as several other histomorphological factors (e.g., keratinization, nuclear size, mitotic activity) in a test cohort (n = 125) and an independent validation cohort (n = 122) of cervical SCC. All parameters were correlated with clinicopathological factors and patient outcome. Small cell nest size and high tumour budding activity were strongly associated with a dismal patient prognosis (p < 0.001 for overall survival [OS], disease-specific survival, and disease-free survival; test cohort) in both cohorts of cervical SCC. A novel grading algorithm combining these two parameters proved to be a highly effective, stage-independent prognosticator in both cohorts (OS: p < 0.001, test cohort; p = 0.001, validation cohort). In the test cohort, multivariate statistical analysis of the novel grade revealed that the hazard ratio (HR) for OS was 2.3 for G2 and 5.1 for G3 tumours compared to G1 neoplasms (p = 0.010). In the validation cohort, HR for OS was 3.0 for G2 and 7.2 for G3 tumours (p = 0.012). In conclusion, our novel grading algorithm incorporating cell nest size and tumour budding allows strongly prognostic histopathological grading of cervical SCC superior to WHO-based grading. Therefore, our data can be regarded as a cross-organ validation of previous results demonstrated for oesophageal, lung, and oral SCC. We suggest this grading algorithm as an additional morphology-based parameter for the routine diagnostic assessment of this tumour entity. © 2018 The Authors The Journal of Pathology: Clinical Research published by The Pathological Society of Great Britain and Ireland and John Wiley & Sons Ltd.

EGFR LI and Ki-67 LI are independent prognostic parameters influencing survivals of surgically treated squamous cell lung cancer patients.

PubMed

Niemiec, J; Kolodziejski, L; Dyczek, S

2005-01-01

In literature there are still opinion differences concerning the prognostic significance of epidermal growth factor receptor (EGFR) expression and proliferative potential in patients with non small cell lung cancer (NSCLC). This prompted us to study those parameters. The Ki-67 labeling index (Ki-67 LI), EGFR labeling index (EGFR LI), and mitotic index (MI) were analyzed in the group of 78 consecutive, surgically treated squamous cell lung cancer (SqCLC) patients. The expression of Ki-67 and EGFR protein was visualized on formalin fixed, paraffin embedded sections using immunohistochemistry (IHC). Mitotic index was assessed on formalin fixed, paraffin embedded sections, stained with hematoxylin and eosin using morphological criteria. Mean values of Ki-67 LI and MI were higher for G2+G3 tumors than for G1 tumors. EGFR LI was higher for G1+G2 than for G3 tumors, and for pT3 than for pT1+pT2 tumors. Patients having tumors with Ki-67 < or =28% or (EGFR LI < or =13% or EGFR LI >80%) survived significantly shorter than those having tumors with Ki-67 LI >28% or 13%< EGFR LI < or =80%. In multivariate analysis, 13%> or = EGFR LI <80% and Ki-67 LI < or =28% were independent negative prognostic parameters influencing survivals of SqCLC patients.

Matrix metalloproteinases in cancer: their value as diagnostic and prognostic markers and therapeutic targets.

PubMed

Hadler-Olsen, Elin; Winberg, Jan-Olof; Uhlin-Hansen, Lars

2013-08-01

Biomarkers are used as tools in cancer diagnostics and in treatment stratification. In most cancers, there are increased levels of one or several members of the matrix metalloproteinases (MMPs). This is a family of proteolytic enzymes that are involved in many phases of cancer progression, including angiogenesis, invasiveness, and metastasis. It has therefore been expected that MMPs could serve as both diagnostic and prognostic markers in cancer patients, but despite a huge number of studies, it has been difficult to establish MMPs as cancer biomarkers. In the present paper, we assess some of the challenges associated with MMP research as well as putative reasons for the conflicting data on the value of these enzymes as diagnostic and prognostic markers in cancer patients. We also review the prognostic value of a number of MMPs in patients with lung, colorectal, breast, and prostate cancers. The review also discusses MMPs as potential target molecules for therapeutic agents and new strategies for development of such drugs.

Prognostic Value of the Amount of Bleeding After Aneurysmal Subarachnoid Hemorrhage: A Quantitative Volumetric Study.

PubMed

Lagares, Alfonso; Jiménez-Roldán, Luis; Gomez, Pedro A; Munarriz, Pablo M; Castaño-León, Ana M; Cepeda, Santiago; Alén, José F

2015-12-01

Quantitative estimation of the hemorrhage volume associated with aneurysm rupture is a new tool of assessing prognosis. To determine the prognostic value of the quantitative estimation of the amount of bleeding after aneurysmal subarachnoid hemorrhage, as well the relative importance of this factor related to other prognostic indicators, and to establish a possible cut-off value of volume of bleeding related to poor outcome. A prospective cohort of 206 patients consecutively admitted with the diagnosis of aneurysmal subarachnoid hemorrhage to Hospital 12 de Octubre were included in the study. Subarachnoid, intraventricular, intracerebral, and total bleeding volumes were calculated using analytic software. For assessing factors related to prognosis, univariate and multivariate analysis (logistic regression) were performed. The relative importance of factors in determining prognosis was established by calculating their proportion of explained variation. Maximum Youden index was calculated to determine the optimal cut point for subarachnoid and total bleeding volume. Variables independently related to prognosis were clinical grade at admission, age, and the different bleeding volumes. The proportion of variance explained is higher for subarachnoid bleeding. The optimal cut point related to poor prognosis is a volume of 20 mL both for subarachnoid and total bleeding. Volumetric measurement of subarachnoid or total bleeding volume are both independent prognostic factors in patients with aneurysmal subarachnoid hemorrhage. A volume of more than 20 mL of blood in the initial noncontrast computed tomography is related to a clear increase in poor outcome risk. : aSAH, aneurysmal subarachnoid hemorrhage.

PITX3 promoter methylation is a prognostic biomarker for biochemical recurrence-free survival in prostate cancer patients after radical prostatectomy.

PubMed

Holmes, Emily Eva; Goltz, Diane; Sailer, Verena; Jung, Maria; Meller, Sebastian; Uhl, Barbara; Dietrich, Jörn; Röhler, Magda; Ellinger, Jörg; Kristiansen, Glen; Dietrich, Dimo

2016-01-01

Molecular biomarkers that might help to distinguish between more aggressive and clinically insignificant prostate cancers (PCa) are still urgently needed. Aberrant DNA methylation as a common molecular alteration in PCa seems to be a promising source for such biomarkers. In this study, PITX3 DNA methylation ( mPITX3 ) and its potential role as a prognostic biomarker were investigated. Furthermore, m PITX3 was analyzed in combination with the established PCa methylation biomarker PITX2 ( mPITX2 ). mPITX3 and mPITX2 were assessed by a quantitative real-time PCR and by means of the Infinium HumanMethylation450 BeadChip. BeadChip data were obtained from The Cancer Genome Atlas (TCGA) Research Network. DNA methylation differences between normal adjacent, benign hyperplastic, and carcinomatous prostate tissues were examined in the TCGA dataset as well as in prostatectomy specimens from the University Hospital Bonn. Retrospective analyses of biochemical recurrence (BCR) were conducted in a training cohort ( n  = 498) from the TCGA and an independent validation cohort ( n  = 300) from the University Hospital Bonn. All patients received radical prostatectomy. In PCa tissue, mPITX3 was increased significantly compared to normal and benign hyperplastic tissue. In univariate Cox proportional hazards analyses, mPITX3 showed a significant prognostic value for BCR (training cohort: hazard ratio (HR) = 1.83 (95 % CI 1.07-3.11), p  = 0.027; validation cohort: HR = 2.56 (95 % CI 1.44-4.54), p  = 0.001). A combined evaluation with PITX2 methylation further revealed that hypermethylation of a single PITX gene member (either PITX2 or PITX3 ) identifies an intermediate risk group. PITX3 DNA methylation alone and in combination with PITX2 is a promising biomarker for the risk stratification of PCa patients and adds relevant prognostic information to common clinically implemented parameters. Further studies are required to determine whether the results are transferable to a biopsy-based patient cohort. Trial registration: Patients for this unregistered study were enrolled retrospectively.

The expression level of BAALC-associated microRNA miR-3151 is an independent prognostic factor in younger patients with cytogenetic intermediate-risk acute myeloid leukemia

PubMed Central

Díaz-Beyá, M; Brunet, S; Nomdedéu, J; Cordeiro, A; Tormo, M; Escoda, L; Ribera, J M; Arnan, M; Heras, I; Gallardo, D; Bargay, J; Queipo de Llano, M P; Salamero, O; Martí, J M; Sampol, A; Pedro, C; Hoyos, M; Pratcorona, M; Castellano, J J; Nomdedeu, M; Risueño, R M; Sierra, J; Monzó, M; Navarro, A; Esteve, J

2015-01-01

Acute myeloid leukemia (AML) is a heterogeneous disease whose prognosis is mainly related to the biological risk conferred by cytogenetics and molecular profiling. In elderly patients (⩾60 years) with normal karyotype AML miR-3151 have been identified as a prognostic factor. However, miR-3151 prognostic value has not been examined in younger AML patients. In the present work, we have studied miR-3151 alone and in combination with BAALC, its host gene, in a cohort of 181 younger intermediate-risk AML (IR-AML) patients. Patients with higher expression of miR-3151 had shorter overall survival (P=0.0025), shorter leukemia-free survival (P=0.026) and higher cumulative incidence of relapse (P=0.082). Moreover, in the multivariate analysis miR-3151 emerged as independent prognostic marker in both the overall series and within the unfavorable molecular prognostic category. Interestingly, the combined determination of both miR-3151 and BAALC improved this prognostic stratification, with patients with low levels of both parameters showing a better outcome compared with those patients harboring increased levels of one or both markers (P=0.003). In addition, we studied the microRNA expression profile associated with miR-3151 identifying a six-microRNA signature. In conclusion, the analysis of miR-3151 and BAALC expression may well contribute to an improved prognostic stratification of younger patients with IR-AML. PMID:26430723

Associations Between PET Textural Features and GLUT1 Expression, and the Prognostic Significance of Textural Features in Lung Adenocarcinoma.

PubMed

Koh, Young Wha; Park, Seong Yong; Hyun, Seung Hyup; Lee, Su Jin

2018-02-01

We evaluated the association between positron emission tomography (PET) textural features and glucose transporter 1 (GLUT1) expression level and further investigated the prognostic significance of textural features in lung adenocarcinoma. We evaluated 105 adenocarcinoma patients. We extracted texture-based PET parameters of primary tumors. Conventional PET parameters were also measured. The relationships between PET parameters and GLUT1 expression levels were evaluated. The association between PET parameters and overall survival (OS) was assessed using Cox's proportional hazard regression models. In terms of PET textural features, tumors expressing high levels of GLUT1 exhibited significantly lower coarseness, contrast, complexity, and strength, but significantly higher busyness. On univariate analysis, the metabolic tumor volume, total lesion glycolysis, contrast, busyness, complexity, and strength were significant predictors of OS. Multivariate analysis showed that lower complexity (HR=2.017, 95%CI=1.032-3.942, p=0.040) was independently associated with poorer survival. PET textural features may aid risk stratification in lung adenocarcinoma patients. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

An internally validated new clinical and inflammation-based prognostic score for patients with advanced hepatocellular carcinoma treated with sorafenib.

PubMed

Diaz-Beveridge, R; Bruixola, G; Lorente, D; Caballero, J; Rodrigo, E; Segura, Á; Akhoundova, D; Giménez, A; Aparicio, J

2018-03-01

Sorafenib is a standard treatment for patients (pts) with advanced hepatocellular carcinoma (aHCC), although the clinical benefit is heterogeneous between different pts groups. Among novel prognostic factors, a low baseline neutrophil-to-lymphocyte ratio (bNLR) and early-onset diarrhoea have been linked with a better prognosis. To identify prognostic factors in pts with aHCC treated with 1st-line sorafenib and to develop a new prognostic score to guide management. Retrospective review of 145 pts bNLR, overall toxicity, early toxicity rates and overall survival (OS) were assessed. Univariate and multivariate analysis of prognostic factors for OS was performed. The prognostic score was calculated from the coefficients found in the Cox analysis. ROC curves and pseudoR2 index were used for internal validation. Discrimination ability and calibration were tested by Harrel's c-index (HCI) and Akaike criteria (AIC). The optimal bNLR cut-off for the prediction of OS was 4 (AUC 0.62). Independent prognostic factors in multivariate analysis for OS were performance status (PS) (p < .0001), Child-Pugh (C-P) score (p = 0.005), early-onset diarrhoea (p = 0.006) and BNLR (0.011). The prognostic score based on these four variables was found efficient (HCI = 0.659; AIC = 1.180). Four risk groups for OS could be identified: a very low-risk (median OS = 48.6 months), a low-risk (median OS = 11.6 months), an intermediate-risk (median OS = 8.3 months) and a high-risk group (median OS = 4.4 months). PS and C-P score were the main prognostic factors for OS, followed by early-onset diarrhoea and bNLR. We identified four risk groups for OS depending on these parameters. This prognostic model could be useful for patient stratification, but an external validation is needed.

Primary central nervous system lymphoma in immunocompetent individuals: a single center experience.

PubMed

Aki, Hilal; Uzunaslan, Didem; Saygin, Caner; Batur, Sebnem; Tuzuner, Nukhet; Kafadar, Ali; Ongoren, Seniz; Oz, Buge

2013-01-01

Primary central nervous system lymphoma (PCNSL) is defined as the involvement of brain, leptomeninges, eyes or spinal cord by non-Hodgkin lymphoma. The role of various prognostic markers in predicting adverse outcome is debated. To investigate the clinical and immunohistochemical findings of immunocompetent PCNSL cases (39 cases) diagnosed at the study center, and evaluate the influence of potential prognostic factors on overall survival (OS) of patients. Data regarding patient characteristics, neuroimaging, pathological and immunohistochemical features and follow-up were obtained from patient records. The influence of potential prognostic parameters on OS was investigated by log-rank test and Cox regression analysis. Patients who received combined chemotherapy and radiotherapy had a significantly better OS when compared to chemotherapy alone. Other variables included in this study were not associated with a significant survival advantage. In this study, we failed to demonstrate a relationship between different clinicopathological variables and OS of patients. Prospective studies with large patient series are needed to investigate other potential prognostic factors.

Model Adaptation for Prognostics in a Particle Filtering Framework

NASA Technical Reports Server (NTRS)

Saha, Bhaskar; Goebel, Kai Frank

2011-01-01

One of the key motivating factors for using particle filters for prognostics is the ability to include model parameters as part of the state vector to be estimated. This performs model adaptation in conjunction with state tracking, and thus, produces a tuned model that can used for long term predictions. This feature of particle filters works in most part due to the fact that they are not subject to the "curse of dimensionality", i.e. the exponential growth of computational complexity with state dimension. However, in practice, this property holds for "well-designed" particle filters only as dimensionality increases. This paper explores the notion of wellness of design in the context of predicting remaining useful life for individual discharge cycles of Li-ion batteries. Prognostic metrics are used to analyze the tradeoff between different model designs and prediction performance. Results demonstrate how sensitivity analysis may be used to arrive at a well-designed prognostic model that can take advantage of the model adaptation properties of a particle filter.

Risk stratification in myelodysplastic syndromes: is there a role for gene expression profiling?

PubMed

Zeidan, Amer M; Prebet, Thomas; Saad Aldin, Ehab; Gore, Steven David

2014-04-01

Evaluation of: Pellagatti A, Benner A, Mills KI et al. Identification of gene expression-based prognostic markers in the hematopoietic stem cells of patients with myelodysplastic syndromes. J. Clin. Oncol. 31(28), 3557-3564 (2013). Patients with myelodysplastic syndromes (MDS) exhibit wide heterogeneity in clinical outcomes making accurate risk-stratification an integral part of the risk-adaptive management paradigm. Current prognostic schemes for MDS rely on clinicopathological parameters. Despite the increasing knowledge of the genetic landscape of MDS and the prognostic impact of many newly discovered molecular aberrations, none to date has been incorporated formally into the major risk models. Efforts are ongoing to use data generated from genome-wide high-throughput techniques to improve the 'individualized' outcome prediction for patients. We here discuss an important paper in which gene expression profiling (GEP) technology was applied to marrow CD34(+) cells from 125 MDS patients to generate and validate a standardized GEP-based prognostic signature.

Low Expression of Mucin-4 Predicts Poor Prognosis in Patients With Clear-Cell Renal Cell Carcinoma

PubMed Central

Fu, Hangcheng; Liu, Yidong; Xu, Le; Chang, Yuan; Zhou, Lin; Zhang, Weijuan; Yang, Yuanfeng; Xu, Jiejie

2016-01-01

Abstract Mucin-4 (MUC4), a member of membrane-bound mucins, has been reported to exert a large variety of distinctive roles in tumorigenesis of different cancers. MUC4 is aberrantly expressed in clear-cell renal cell carcinoma (ccRCC) but its prognostic value is still unveiled. This study aims to assess the clinical significance of MUC4 expression in patients with ccRCC. The expression of MUC4 was assessed by immunohistochemistry in 198 patients with ccRCC who underwent nephrectomy retrospectively in 2003 and 2004. Sixty-seven patients died before the last follow-up in the cohort. Kaplan–Meier method with log-rank test was applied to compare survival curves. Univariate and multivariate Cox regression models were applied to evaluate the prognostic value of MUC4 expression in overall survival (OS). The predictive nomogram was constructed based on the independent prognostic factors. The calibration was built to evaluate the predictive accuracy of nomogram. In patients with ccRCC, MUC4 expression, which was determined to be an independent prognostic indicator for OS (hazard ratio [HR] 3.891; P < 0.001), was negatively associated with tumor size (P = 0.036), Fuhrman grade (P = 0.044), and OS (P < 0.001). The prognostic accuracy of TNM stage, UCLA Integrated Scoring System (UISS), and Mayo clinic stage, size, grade, and necrosis score (SSIGN) prognostic models was improved when MUC4 expression was added. The independent prognostic factors, pT stage, distant metastases, Fuhrman grade, sarcomatoid, and MUC4 expression were integrated to establish a predictive nomogram with high predictive accuracy. MUC4 expression is an independent prognostic factor for OS in patients with ccRCC. PMID:27124015

Serum total hCGβ level is an independent prognostic factor in transitional cell carcinoma of the urothelial tract.

PubMed

Douglas, J; Sharp, A; Chau, C; Head, J; Drake, T; Wheater, M; Geldart, T; Mead, G; Crabb, S J

2014-04-02

Serum total human chorionic gonadotrophin β subunit (hCGβ) level might have prognostic value in urothelial transitional cell carcinoma (TCC) but has not been investigated for independence from other prognostic variables. We utilised a clinical database of patients receiving chemotherapy between 2005 and 2011 for urothelial TCC and an independent cohort of radical cystectomy patients for validation purposes. Prognostic variables were tested by univariate Kaplan-Meier analyses and log-rank tests. Statistically significant variables were then assessed by multivariate Cox regression. Total hCGβ level was dichotomised at < vs ≥2 IU l(-1). A total of 235 chemotherapy patients were eligible. For neoadjuvant chemotherapy, established prognostic factors including low ECOG performance status, normal haemoglobin, lower T stage and suitability for cisplatin-based chemotherapy were associated with favourable survival in univariate analyses. In addition, low hCGβ level was favourable when assessed either before (median survival not reached vs 1.86 years, P=0.001) or on completion of chemotherapy (4.27 vs 0.42 years, P=0.000002). This was confirmed in multivariate analyses and in patients receiving first- and second-line palliative chemotherapy, and in a radical cystectomy validation set. Serum total hCGβ level is an independent prognostic factor in patients receiving chemotherapy for urothelial TCC in both curative and palliative settings.

Prognostic value of Child-Turcotte criteria in medically treated cirrhosis.

PubMed

Christensen, E; Schlichting, P; Fauerholdt, L; Gluud, C; Andersen, P K; Juhl, E; Poulsen, H; Tygstrup, N

1984-01-01

The Child- Turcotte criteria (CTC) (based on serum bilirubin and albumin, ascites, neurological disorder and nutrition) are established prognostic factors in patients with cirrhosis having portacaval shunt surgery. The objective of this study was to evaluate the prognostic value of CTC in conservatively treated cirrhosis. Patients (n = 245) with histologically verified cirrhosis from a control group of a controlled clinical trial were studied. Data at entry into the trial were used to classify patients according to CTC. Survival curves for up to 16 years were made, and survival rates were compared using the log-rank test. Survival decreased significantly with increasing degree of abnormality (A----B----C) of albumin (p less than 0.001), ascites (p less than 0.001), bilirubin (p = 0.02) and nutritional status (p = 0.03). Survival was insignificantly influenced by neurological status (p = 0.11) probably because none of the patients had hepatic coma at entry into the trial. The five variables in CTC were combined to a score. With increasing score, the median survival time decreased from 6.4 years (score 5) to 2 months (scores 12 or more). Furthermore, the mortality from hepatic failure, gastrointestinal bleeding or hepatocellular carcinoma increased significantly with increasing score. CTC provide valuable and easily obtainable prognostic information in cirrhosis. However, CTC are inferior to a prognostic index based on multivariate analysis of prognostic factors.

The prognostic reliability of intracranial pressure monitoring and MRI data in severe traumatic brain injury.

PubMed

Woischneck, Dieter; Kapapa, Thomas

2017-02-01

The predictive quality of intracranial pressure (ICP) monitoring has for many years been a matter of debate. We correlate ICP data comparing MRI data with the outcome after severe traumatic brain injury to evaluate their prognostic potency. This study compares the results of ICP monitoring, MRI, coma duration and outcome according to Glasgow Outcome Scale obtained in 32 patients having suffered severe TBI. Level of significance was set to p≤0.05 in statistical tests. The MRI results were closely correlated with coma duration and Glasgow Outcome Scale, but the ICP measurements were not. With the exception of severe, bipontine lesions, there is no other region of the brain in which increased evidence of traumatogenic lesions emerges as the intracranial pressure rises. Just bipontine lesions that proof to be infaust correlate with elevated ICP values. ICP monitoring does not allow individual prognostic conclusions to be made. Implantation of an intracranial pressure sensor alone for making a prognostic estimate is not advisable. The use of intracranial pressure measurements in the retrospective appraisal of disease progress is highly problematic. However, MRI diagnostic in patients with severe TBI improves prognostic potency of clinical parameters. Copyright © 2016 Elsevier Inc. All rights reserved.

Supervised Risk Predictor of Breast Cancer Based on Intrinsic Subtypes

PubMed Central

Parker, Joel S.; Mullins, Michael; Cheang, Maggie C.U.; Leung, Samuel; Voduc, David; Vickery, Tammi; Davies, Sherri; Fauron, Christiane; He, Xiaping; Hu, Zhiyuan; Quackenbush, John F.; Stijleman, Inge J.; Palazzo, Juan; Marron, J.S.; Nobel, Andrew B.; Mardis, Elaine; Nielsen, Torsten O.; Ellis, Matthew J.; Perou, Charles M.; Bernard, Philip S.

2009-01-01

Purpose To improve on current standards for breast cancer prognosis and prediction of chemotherapy benefit by developing a risk model that incorporates the gene expression–based “intrinsic” subtypes luminal A, luminal B, HER2-enriched, and basal-like. Methods A 50-gene subtype predictor was developed using microarray and quantitative reverse transcriptase polymerase chain reaction data from 189 prototype samples. Test sets from 761 patients (no systemic therapy) were evaluated for prognosis, and 133 patients were evaluated for prediction of pathologic complete response (pCR) to a taxane and anthracycline regimen. Results The intrinsic subtypes as discrete entities showed prognostic significance (P = 2.26E-12) and remained significant in multivariable analyses that incorporated standard parameters (estrogen receptor status, histologic grade, tumor size, and node status). A prognostic model for node-negative breast cancer was built using intrinsic subtype and clinical information. The C-index estimate for the combined model (subtype and tumor size) was a significant improvement on either the clinicopathologic model or subtype model alone. The intrinsic subtype model predicted neoadjuvant chemotherapy efficacy with a negative predictive value for pCR of 97%. Conclusion Diagnosis by intrinsic subtype adds significant prognostic and predictive information to standard parameters for patients with breast cancer. The prognostic properties of the continuous risk score will be of value for the management of node-negative breast cancers. The subtypes and risk score can also be used to assess the likelihood of efficacy from neoadjuvant chemotherapy. PMID:19204204

Prevalence and prognostic impact of allelic imbalances associated with leukemic transformation of Philadelphia chromosome–negative myeloproliferative neoplasms

PubMed Central

Krug, Utz O.; Lee, Dhong Hyun Tony; Kawamata, Norihiko; Iwanski, Gabriela B.; Lasho, Terra; Weiss, Tamara; Nowak, Daniel; Koren-Michowitz, Maya; Kato, Motohiro; Sanada, Masashi; Shih, Lee-Yung; Nagler, Arnon; Raynaud, Sophie D.; Müller-Tidow, Carsten; Mesa, Ruben; Haferlach, Torsten; Gilliland, D. Gary; Tefferi, Ayalew; Ogawa, Seishi; Koeffler, H. Phillip

2010-01-01

Philadelphia chromosome–negative myeloproliferative neoplasms (MPNs) including polycythemia vera, essential thrombocythemia, and primary myelofibrosis show an inherent tendency for transformation into leukemia (MPN-blast phase), which is hypothesized to be accompanied by acquisition of additional genomic lesions. We, therefore, examined chromosomal abnormalities by high-resolution single nucleotide polymorphism (SNP) array in 88 MPN patients, as well as 71 cases with MPN-blast phase, and correlated these findings with their clinical parameters. Frequent genomic alterations were found in MPN after leukemic transformation with up to 3-fold more genomic changes per sample compared with samples in chronic phase (P < .001). We identified commonly altered regions involved in disease progression including not only established targets (ETV6, TP53, and RUNX1) but also new candidate genes on 7q, 16q, 19p, and 21q. Moreover, trisomy 8 or amplification of 8q24 (MYC) was almost exclusively detected in JAK2V617F− cases with MPN-blast phase. Remarkably, copy number–neutral loss of heterozygosity (CNN-LOH) on either 7q or 9p including homozygous JAK2V617F was related to decreased survival after leukemic transformation (P = .01 and P = .016, respectively). Our high-density SNP-array analysis of MPN genomes in the chronic compared with leukemic stage identified novel target genes and provided prognostic insights associated with the evolution to leukemia. PMID:20068225

Prognostic significance of DSG3 in rectal adenocarcinoma treated with preoperative chemoradiotherapy.

PubMed

Chao, Tung-Bo; Li, Chien-Feng; Lin, Ching-Yih; Tian, Yu-Feng; Chang, I-Wei; Sheu, Ming-Jen; Lee, Ying-En; Chan, Ti-Chun; He, Hong-Lin

2016-06-01

This study aimed to investigate the prognostic significance of DSG3 and its association with response to neoadjuvant concurrent chemoradiotherapy (CCRT) in rectal cancer. Data mining of a publicly available dataset was performed to find genes associated with CCRT response. Immunohistochemistry was applied to evaluate DSG3 expression. The relationships between DSG3 expression and various clinicopathological parameters and survival were analyzed. The DSG3 gene was significantly associated with CCRT response. The expression of DSG3 negatively correlated with poorer tumor regression (p < 0.001) and had an independent negative impact on disease-specific survival (p = 0.011), local recurrence-free survival (p = 0.031) and metastasis-free survival (p = 0.029). DSG3 was a key prognostic factor and predictor for CCRT response in rectal cancer patients.

[THERMAL STABILITY AS A PROGNOSTIC INDICATOR OF CONSERVATION OF LIVE EMBRYONIC SMALLPOX VACCINE (TEOVAC) DURING STORAGE].

PubMed

Zhukov, V A; Kokorev, S V; Rogozhkina, S V; Melnikov, D G; Terentiev, A I; Kovalchuk, E A; Vakhnov, E Yu; Borisevich, S V

2016-01-01

Determination of values of coefficients of thermal stability of TEOVac for prognosis of conservation of the vaccine (specific biological activity) during the process of warranty period storage. TEOVac (masticatory tablets) in primary packaging was kept at increased temperature (accelerated and stress-tests) and at the conditions established by PAP for the preparation (long-term tests). Biological activity of the vaccine was determined by titration on 12-day chicken embryos. A correlation between the value of coefficients of thermal stability and conservation of the prepared series of the condition preparation at the final date of storage was experimentally established. Coefficients of thermal stability could be used as a prognostic indicator of quality of the produced pelleted formulation of the preparation for evaluation of conservation of the vaccine during warranty period storage.

Investigation of polymer electrolyte membrane fuel cell internal behaviour during long term operation and its use in prognostics

NASA Astrophysics Data System (ADS)

Mao, Lei; Jackson, Lisa; Jackson, Tom

2017-09-01

This paper investigates the polymer electrolyte membrane (PEM) fuel cell internal behaviour variation at different operating condition, with characterization test data taken at predefined inspection times, and uses the determined internal behaviour evolution to predict the future PEM fuel cell performance. For this purpose, a PEM fuel cell behaviour model is used, which can be related to various fuel cell losses. By matching the model to the collected polarization curves from the PEM fuel cell system, the variation of fuel cell internal behaviour can be obtained through the determined model parameters. From the results, the source of PEM fuel cell degradation during its lifetime at different conditions can be better understood. Moreover, with determined fuel cell internal behaviour, the future fuel cell performance can be obtained by predicting the future model parameters. By comparing with prognostic results using adaptive neuro fuzzy inference system (ANFIS), the proposed prognostic analysis can provide better predictions for PEM fuel cell performance at dynamic condition, and with the understanding of variation in PEM fuel cell internal behaviour, mitigation strategies can be designed to extend the fuel cell performance.

Prediction of outcome using pretreatment 18F-FDG PET/CT and MRI radiomics in locally advanced cervical cancer treated with chemoradiotherapy.

PubMed

Lucia, François; Visvikis, Dimitris; Desseroit, Marie-Charlotte; Miranda, Omar; Malhaire, Jean-Pierre; Robin, Philippe; Pradier, Olivier; Hatt, Mathieu; Schick, Ulrike

2018-05-01

The aim of this study is to determine if radiomics features from 18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) and magnetic resonance imaging (MRI) images could contribute to prognoses in cervical cancer. One hundred and two patients (69 for training and 33 for testing) with locally advanced cervical cancer (LACC) receiving chemoradiotherapy (CRT) from 08/2010 to 12/2016 were enrolled in this study. 18 F-FDG PET/CT and MRI examination [T1, T2, T1C, diffusion-weighted imaging (DWI)] were performed for each patient before CRT. Primary tumor volumes were delineated with the fuzzy locally adaptive Bayesian algorithm in the PET images and with 3D Slicer™ in the MRI images. Radiomics features (intensity, shape, and texture) were extracted and their prognostic value was compared with clinical parameters for recurrence-free and locoregional control. In the training cohort, median follow-up was 3.0 years (range, 0.43-6.56 years) and relapse occurred in 36% of patients. In univariate analysis, FIGO stage (I-II vs. III-IV) and metabolic response (complete vs. non-complete) were probably associated with outcome without reaching statistical significance, contrary to several radiomics features from both PET and MRI sequences. Multivariate analysis in training test identified Grey Level Non Uniformity GLRLM in PET and Entropy GLCM in ADC maps from DWI MRI as independent prognostic factors. These had significantly higher prognostic power than clinical parameters, as evaluated in the testing cohort with accuracy of 94% for predicting recurrence and 100% for predicting lack of loco-regional control (versus ~50-60% for clinical parameters). In LACC treated with CRT, radiomics features such as EntropyGLCM and GLNUGLRLM from functional imaging DWI-MRI and PET, respectively, are independent predictors of recurrence and loco-regional control with significantly higher prognostic power than usual clinical parameters. Further research is warranted for their validation, which may justify more aggressive treatment in patients identified with high probability of recurrence.

Human papillomavirus reduces the prognostic value of nodal involvement in tonsillar squamous cell carcinomas.

PubMed

Straetmans, Jos M J A A; Olthof, Nadine; Mooren, Jeroen J; de Jong, Jos; Speel, Ernst-Jan M; Kremer, Bernd

2009-10-01

Assessment of the prognostic value of nodal status in relation to human papillomavirus (HPV) status and the various treatment modalities in tonsillar squamous cell carcinomas (TSCC). Retrospective 5-year survival analysis. A 5-year follow-up of disease-free, disease-specific, and overall survival in a group of 81 patients with TSCC was conducted. The nodal status and integration of HPV-DNA in the genome (detected with fluorescence in situ hybridization) as prognostic indicators were examined while correcting for other clinical parameters (smoking habits, alcohol consumption, treatment modality, differentiation, TNM classification). Of TSCCs, 41% were positive for HPV type 16. In these TSCCs, the primary tumor was significantly smaller when compared to HVP-negative TSCCs (P = .04), whereas the percentage of cases with cervical metastases was identical. In the total population, it was not nodal involvement, but rather HPV manifestation, which was related to patient prognosis. Within the treatment modalities (surgery combined with radiotherapy and radiotherapy alone), neither nodal status nor HPV were prognostic indicators. Since a substantial percentage of TSCCs are HPV-positive and metastasizes to cervical lymph nodes in less advanced primary tumors, the N status is an unreliable prognostic indicator in TSCCs. HPV is only prognostically relevant in the total tumor population, but loses its value within patient groups receiving a single treatment modality. The value of HPV for prognosis of patients with TSCC requires further study.

CD25 expression status improves prognostic risk classification in AML independent of established biomarkers: ECOG phase 3 trial, E1900

PubMed Central

Gönen, Mithat; Sun, Zhuoxin; Figueroa, Maria E.; Patel, Jay P.; Abdel-Wahab, Omar; Racevskis, Janis; Ketterling, Rhett P.; Fernandez, Hugo; Rowe, Jacob M.; Tallman, Martin S.; Melnick, Ari; Levine, Ross L.

2012-01-01

We determined the prognostic relevance of CD25 (IL-2 receptor-α) expression in 657 patients (≤ 60 years) with de novo acute myeloid leukemia (AML) treated in the Eastern Cooperative Oncology Group trial, E1900. We identified CD25POS myeloblasts in 87 patients (13%), of whom 92% had intermediate-risk cytogenetics. CD25 expression correlated with expression of stem cell antigen CD123. In multivariate analysis, controlled for prognostic baseline characteristics and daunorubicin dose, CD25POS patients had inferior complete remission rates (P = .0005) and overall survival (P < .0001) compared with CD25NEG cases. In a subset of 396 patients, we integrated CD25 expression with somatic mutation status to determine whether CD25 impacted outcome independent of prognostic mutations. CD25 was positively correlated with internal tandem duplications in FLT3 (FLT3-ITD), DNMT3A, and NPM1 mutations. The adverse prognostic impact of FLT3-ITDPOS AML was restricted to CD25POS patients. CD25 expression improved AML prognostication independent of integrated, cytogenetic and mutational data, such that it reallocated 11% of patients with intermediate-risk disease to the unfavorable-risk group. Gene expression analysis revealed that CD25POS status correlated with the expression of previously reported leukemia stem cell signatures. We conclude that CD25POS status provides prognostic relevance in AML independent of known biomarkers and is correlated with stem cell gene-expression signatures associated with adverse outcome in AML. PMID:22855599

A Comparison of Systemic Inflammation-Based Prognostic Scores in Patients on Regular Hemodialysis

PubMed Central

Kato, Akihiko; Tsuji, Takayuki; Sakao, Yukitoshi; Ohashi, Naro; Yasuda, Hideo; Fujimoto, Taiki; Takita, Takako; Furuhashi, Mitsuyoshi; Kumagai, Hiromichi

2013-01-01

Background/Aims Systemic inflammation-based prognostic scores have prognostic power in patients with cancer, independently of tumor stage and site. Although inflammatory status is associated with mortality in hemodialysis (HD) patients, it remains to be determined as to whether these composite scores are useful in predicting clinical outcomes. Methods We calculated the 6 prognostic scores [Glasgow prognostic score (GPS), modified GPS (mGPS), neutrophil-lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), prognostic index (PI) and prognostic nutritional index (PNI), which have been established as a useful scoring system in cancer patients. We enrolled 339 patients on regular HD (age: 64 ± 13 years; time on HD: 129 ± 114 months; males/females = 253/85) and followed them for 42 months. The area under the receiver-operating characteristics curve was used to determine which scoring system was more predictive of mortality. Results Elevated GPS, mGPS, NLR, PLR, PI and PNI were all associated with total mortality, independent of covariates. If GPS was raised, mGPS, NLR, PLR and PI were also predictive of all-cause mortality and/or hospitalization. GPS and PNI were associated with poor nutritional status. Using overall mortality as an endpoint, the area under the curve (AUC) was significant for a GPS of 0.701 (95% CI: 0.637-0.765; p < 0.01) and for a PNI of 0.616 (95% CI: 0.553-0.768; p = 0.01). However, AUC for hypoalbuminemia (<3.5 g/dl) was comparable to that of GPS (0.695, 95% CI: 0.632-0.759; p < 0.01). Conclusion GPS, based on serum albumin and highly sensitive C-reactive protein, has the most prognostic power for mortality prediction among the prognostic scores in HD patients. However, as the determination of serum albumin reflects mortality similarly to GPS, other composite combinations are needed to provide additional clinical utility beyond that of albumin alone in HD patients. PMID:24403910

Baseline Metabolic Tumor Volume and Total Lesion Glycolysis Are Associated With Survival Outcomes in Patients With Locally Advanced Pancreatic Cancer Receiving Stereotactic Body Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dholakia, Avani S.; Chaudhry, Muhammad; Leal, Jeffrey P.

2014-07-01

Purpose: Although previous studies have demonstrated the prognostic value of positron emission tomography (PET) parameters in other malignancies, the role of PET in pancreatic cancer has yet to be well established. We analyzed the prognostic utility of PET for patients with locally advanced pancreatic cancer (LAPC) undergoing fractionated stereotactic body radiation therapy (SBRT). Materials and Methods: Thirty-two patients with LAPC in a prospective clinical trial received up to 3 doses of gemcitabine, followed by 33 Gy in 5 fractions of 6.6 Gy, using SBRT. All patients received a baseline PET scan prior to SBRT (pre-SBRT PET). Metabolic tumor volume (MTV), total lesionmore » glycolysis (TLG), and maximum and peak standardized uptake values (SUV{sub max} and SUV{sub peak}) on pre-SBRT PET scans were calculated using custom-designed software. Disease was measured at a threshold based on the liver SUV, using the equation Liver{sub mean} + [2 × Liver{sub sd}]. Median values of PET parameters were used as cutoffs when assessing their prognostic potential through Cox regression analyses. Results: Of the 32 patients, the majority were male (n=19, 59%), 65 years or older (n=21, 66%), and had tumors located in the pancreatic head (n=27, 84%). Twenty-seven patients (84%) received induction gemcitabine prior to SBRT. Median overall survival for the entire cohort was 18.8 months (95% confidence interval [CI], 15.7-22.0). An MTV of 26.8 cm{sup 3} or greater (hazard ratio [HR] 4.46, 95% CI 1.64-5.88, P<.003) and TLG of 70.9 or greater (HR 3.08, 95% CI 1.18-8.02, P<.021) on pre-SBRT PET scan were associated with inferior overall survival on univariate analysis. Both pre-SBRT MTV (HR 5.13, 95% CI 1.19-22.21, P=.029) and TLG (HR 3.34, 95% CI 1.07-10.48, P=.038) remained independently associated with overall survival in separate multivariate analyses. Conclusions: Pre-SBRT MTV and TLG are potential predictive factors for overall survival in patients with LAPC and may assist in tailoring therapy.« less

Current update on established and novel biomarkers in salivary gland carcinoma pathology and the molecular pathways involved.

PubMed

Stenner, Markus; Klussmann, J Peter

2009-03-01

This review aims to take stock of the new information that has accumulated over the past decade on the molecular pathology of salivary gland cancer. Emphasis will be placed on established and novel immunohistochemical markers, the pathways involved, and on findings of prognostic importance as well as new therapeutic concepts. Whenever reasonable, analogies to tumors of better explored, histologically related glandular organs such as pancreas and breast are established.

Lifecycle Prognostics Architecture for Selected High-Cost Active Components

DOE Office of Scientific and Technical Information (OSTI.GOV)

N. Lybeck; B. Pham; M. Tawfik

There are an extensive body of knowledge and some commercial products available for calculating prognostics, remaining useful life, and damage index parameters. The application of these technologies within the nuclear power community is still in its infancy. Online monitoring and condition-based maintenance is seeing increasing acceptance and deployment, and these activities provide the technological bases for expanding to add predictive/prognostics capabilities. In looking to deploy prognostics there are three key aspects of systems that are presented and discussed: (1) component/system/structure selection, (2) prognostic algorithms, and (3) prognostics architectures. Criteria are presented for component selection: feasibility, failure probability, consequences of failure,more » and benefits of the prognostics and health management (PHM) system. The basis and methods commonly used for prognostics algorithms are reviewed and summarized. Criteria for evaluating PHM architectures are presented: open, modular architecture; platform independence; graphical user interface for system development and/or results viewing; web enabled tools; scalability; and standards compatibility. Thirteen software products were identified and discussed in the context of being potentially useful for deployment in a PHM program applied to systems in a nuclear power plant (NPP). These products were evaluated by using information available from company websites, product brochures, fact sheets, scholarly publications, and direct communication with vendors. The thirteen products were classified into four groups of software: (1) research tools, (2) PHM system development tools, (3) deployable architectures, and (4) peripheral tools. Eight software tools fell into the deployable architectures category. Of those eight, only two employ all six modules of a full PHM system. Five systems did not offer prognostic estimates, and one system employed the full health monitoring suite but lacked operations and maintenance support. Each product is briefly described in Appendix A. Selection of the most appropriate software package for a particular application will depend on the chosen component, system, or structure. Ongoing research will determine the most appropriate choices for a successful demonstration of PHM systems in aging NPPs.« less

Primary Neuroendocrine Carcinoma of the Breast: Histopathological Criteria, Prognostic Factors, and Review of the Literature

PubMed Central

Marinova, Lena; Vicheva, Snezhinka

2016-01-01

We present here a case of a 42-year-old woman diagnosed with primary neuroendocrine carcinoma of the breast (NECB). We discuss the importance of histological criteria for primary neuroendocrine mammary carcinoma, established by WHO in 2003 and 2012. After an overview of different cases of primary neuroendocrine carcinoma of the breast published in the literature, we present information about differential diagnosis, prognostic factors, and surgical and adjuvant treatment. Prognosis of NECB is not different from that of other invasive breast carcinomas and the most important prognostic factor is tumor grade (G). There is no standard treatment and patients should be treated similarly to patients with invasive ductal carcinoma, NOS (not otherwise specified), whose choice of therapy depends on tumor's size, degree of differentiation, clinical stage, and hormonal status. PMID:27840759

Parametric response mapping cut-off values that predict survival of hepatocellular carcinoma patients after TACE.

PubMed

Nörthen, Aventinus; Asendorf, Thomas; Shin, Hoen-Oh; Hinrichs, Jan B; Werncke, Thomas; Vogel, Arndt; Kirstein, Martha M; Wacker, Frank K; Rodt, Thomas

2018-04-21

Parametric response mapping (PRM) is a novel image-analysis technique applicable to assess tumor viability and predict intrahepatic recurrence of hepatocellular carcinoma (HCC) patients treated with transarterial chemoembolization (TACE). However, to date, the prognostic value of PRM for prediction of overall survival in HCC patients undergoing TACE is unclear. The objective of this explorative, single-center study was to identify cut-off values for voxel-specific PRM parameters that predict the post TACE overall survival in HCC patients. PRM was applied to biphasic CT data obtained at baseline and following 3 TACE treatments of 20 patients with HCC tumors ≥ 2 cm. The individual portal venous phases were registered to the arterial phases followed by segmentation of the largest lesion, i.e., the region of interest (ROI). Segmented voxels with their respective arterial and portal venous phase density values were displayed as a scatter plot. Voxel-specific PRM parameters were calculated and compared to patients' survival at 1, 2, and 3 years post treatment to identify the maximal predictive parameters. The hypervascularized tissue portion of the ROI was found to represent an independent predictor of the post TACE overall survival. For this parameter, cut-off values of 3650, 2057, and 2057 voxels, respectively, were determined to be optimal to predict overall survival at 1, 2, and 3 years after TACE. Using these cut points, patients were correctly classified as having died with a sensitivity of 80, 92, and 86% and as still being alive with a specificity of 60, 75, and 83%, respectively. The prognostic accuracy measured by area under the curve (AUC) values ranged from 0.73 to 0.87. PRM may have prognostic value to predict post TACE overall survival in HCC patients.

GLUT-1 Expression in Proliferative Endometrium, Endometrial Hyperplasia, Endometrial Adenocarcinoma and the Relationship Between GLUT-1 Expression and Prognostic Parameters in Endometrial Adenocarcinoma.

PubMed

Canpolat, Tuba; Ersöz, Canan; Uğuz, Aysun; Vardar, Mehmet Ali; Altintaş, Aytekin

2016-01-01

Malignant cells show increased glucose uptake in in vitro and in vivo studies. This uptake is mediated by glucose transporter proteins. GLUT-1 is the most common transporter protein, and its expression is reported to be increase in many human cancers. The aim of this study is to determine the GLUT-1 overexpression in benign, hyperplastic, and malignant endometrial tissues, to evaluate the usefulness of GLUT-1 expression in endometrial hyperplasia, and to determine its role in the neoplastic progression to endometrioid type adenocarcinoma. We also aimed to analyze prognostic clinical parameters, predict prognosis, and survival. We examined immunohistochemical expression of GLUT-1 in 91 cases of endometrial hyperplasia, 100 cases of endometrioid type adenocarcinoma, and 10 proliferative endometrial tissues. The percentage of positive cells and staining intensity were assessed in a semi quantitative fashion and scored (1+ to 3+). GLUT-1 immunoreactivity was not present in proliferative endometrium. Twenty-nine (31.9%) of 91 endometrial hyperplasia cases showed positive immunoreactivity, of which only six were cases of hyperplasia without atypia while 23 of them were cases with atypia. We found GLUT-1 positivity of 95% in endometrioid type adenocarcinoma. GLUT-1 overexpression was not significantly correlated with any of the clinicopathological parameters except histological grade in endometrioid adenocarcinoma; the survival was not found to be correlated with GLUT-1 expression. GLUT-1 immunostaining may be useful in distinguishing hyperplasia without atypia from hyperplasia with atypia; GLUT-1 overexpression is a consistent feature of endometrioid adenocarcinoma. A correlation between GLUT -1 expression and tumor grade has been found, although other prognostic parameters and survival has no meaningful correlation.

Skeletal muscle radiodensity is prognostic for survival in patients with advanced non-small cell lung cancer.

PubMed

Sjøblom, Bjørg; Grønberg, Bjørn H; Wentzel-Larsen, Tore; Baracos, Vickie E; Hjermstad, Marianne J; Aass, Nina; Bremnes, Roy M; Fløtten, Øystein; Bye, Asta; Jordhøy, Marit

2016-12-01

Recent research indicates that severe muscular depletion (sarcopenia) is frequent in cancer patients and linked to cachexia and poor survival. Our aim was to investigate if measures of skeletal muscle hold prognostic information in advanced non-small cell lung cancer (NSCLC). We included NSCLC patients with disease stage IIIB/IV, performance status 0-2, enrolled in three randomised trials of first-line chemotherapy (n = 1305). Computed tomography (CT) images obtained before start of treatment were used for body composition analyses at the level of the third lumbar vertebra (L3). Skeletal muscle mass was assessed by measures of the cross sectional muscle area, from which the skeletal muscle index (SMI) was obtained. Skeletal muscle radiodensity (SMD) was measured as the mean Hounsfield unit (HU) of the measured muscle area. A high level of mean HU indicates a high SMD. Complete data were available for 734 patients, mean age 65 years. Both skeletal muscle index (SMI) and muscle radiodensity (SMD) varied largely. Mean SMI and SMD were 47.7 cm 2 /m 2 and 37.4 HU in men (n = 420), 39.6 cm 2 /m 2 and 37.0 HU in women (n = 314). Multivariable Cox regression analyses, adjusted for established prognostic factors, showed that SMD was independently prognostic for survival (Hazard ratio (HR) 0.98, 95% CI 0.97-0.99, p = 0.001), whereas SMI was not (HR 0.99, 95% CI 0.98-1.01, p = 0.329). Low SMD is associated with poorer survival in advanced NSCLC. Further research is warranted to establish whether muscle measures should be integrated into routine practice to improve prognostic accuracy. Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Conditional Disease-Free Survival After Surgical Resection of Gastrointestinal Stromal Tumors

PubMed Central

Bischof, Danielle A.; Kim, Yuhree; Dodson, Rebecca; Jimenez, M. Carolina; Behman, Ramy; Cocieru, Andrei; Fisher, Sarah B.; Groeschl, Ryan T.; Squires, Malcolm H.; Maithel, Shishir K.; Blazer, Dan G.; Kooby, David A.; Gamblin, T. Clark; Bauer, Todd W.; Quereshy, Fayez A.; Karanicolas, Paul J.; Law, Calvin H. L.; Pawlik, Timothy M.

2015-01-01

IMPORTANCE Gastrointestinal stromal tumors (GISTs) are the most commonly diagnosed mesenchymal tumors of the gastrointestinal tract. The risk of recurrence following surgical resection of GISTs is typically reported from the date of surgery. However, disease-free survival (DFS) over time is dynamic and changes based on disease-free time already accumulated following surgery. OBJECTIVES To assess the comparative performance of established GIST recurrence risk prognostic scoring systems and to characterize conditional DFS following surgical resection of GISTs. DESIGN, SETTING, AND PARTICIPANTS A retrospective cohort study of 502 patients who underwent surgery for a primary, nonmetastatic GIST between January 1, 1998, and December 31, 2012, at 7 major academic cancer centers in the United States and Canada. MAIN OUTCOMES AND MEASURES Disease-free survival of the patients was classified according to 5 prognostic scoring systems, including the National Institutes of Health criteria, modified National Institutes of Health criteria, Memorial Sloan Kettering Cancer Center GIST nomogram, and American Joint Committee on Cancer gastric and nongastric categories. The concordance index (also known as the C statistic or the area under the receiver operating curve) of established GIST recurrence risk prognostic scoring systems. Conditional DFS estimates were calculated. RESULTS Overall 1-year, 3-year, and 5-year DFS following resection of GISTs was 95%, 83%, and 74%, respectively. All the prognostic scoring systems had fair prognostic ability. For all tumor sites, the American Joint Committee on Cancer gastric category demonstrated the best discrimination (C = 0.79). Using conditional DFS, the probability of remaining disease free for an additional 3 years given that a patient was disease free at 1 year, 3 years, and 5 years was 82%, 89%, and 92%, respectively. Patients with the highest initial recurrence risk demonstrated the greatest increase in conditional survival as time elapsed. CONCLUSIONS AND RELEVANCE Conditional DFS improves over time following resection of GISTs. This is valuable information about long-term prognosis to communicate to patients who are disease free after a period following surgery. PMID:25671681

[Prognosis in pediatric traumatic brain injury. A dynamic cohort study].

PubMed

Vázquez-Solís, María G; Villa-Manzano, Alberto I; Sánchez-Mosco, Dalia I; Vargas-Lares, José de Jesús; Plascencia-Fernández, Irma

2013-01-01

traumatic brain injury is a main cause of hospital admission and death in children. Our objective was to identify prognostic factors of pediatric traumatic brain injury. this was a dynamic cohort study of traumatic brain injury with 6 months follow-up. The exposition was: mild or moderate/severe traumatic brain injury, searching for prognosis (morbidity-mortality and decreased Glasgow scale). Relative risk and logistic regression was estimated for prognostic factors. we evaluated 440 patients with mild traumatic brain injury and 98 with moderate/severe traumatic brain injury. Morbidity for mild traumatic brain injury was 1 %; for moderate/severe traumatic brain injury, 5 %. There were no deaths. Prognostic factors for moderate/severe traumatic brain injury were associated injuries (RR = 133), fractures (RR = 60), street accidents (RR = 17), night time accidents (RR = 2.3) and weekend accidents (RR = 2). Decreased Glasgow scale was found in 9 %, having as prognostic factors: visible injuries (RR = 3), grown-up supervision (RR = 2.5) and time of progress (RR = 1.6). there should be a prognosis established based on kinetic energy of the injury and not only with Glasgow Scale.

Audiophonological results after cochlear implantation in 40 congenitally deaf patients: preliminary results.

PubMed

Loundon, N; Busquet, D; Roger, G; Moatti, L; Garabedian, E N

2000-11-30

The aim of this study is to evaluate the prognostic factors of audiophonological results in cochlear implant in congenitally deaf patients. Between 1991 and 1996. 40 congenitally deaf children underwent cochlear implantation in our department, at an average age of 7 years (median: 5 years). The results of speech therapy were evaluated with a mean follow-up of 2 years and were classified according to four criteria: perception of sound, speech perception, speech production and the level of oral language. For each criterion, a score was established ranging from zero to four. These scores were weighted according to age such that the results before and after implantation only reflected the changes related to the implantation. The prognostic factors for good results were: a good level of oral communication before implantation, residual hearing, progressive deafness and implantation at a young age. On the other hand, poor prognostic factors were: the presence of behavioral disorders and poor communication skills prior to implantation. Overall, the major prognostic factor for a good outcome appeared to be the preoperative level of oral language, even if this was rudimentary.

Utility of Inflammatory Marker- and Nutritional Status-based Prognostic Factors for Predicting the Prognosis of Stage IV Gastric Cancer Patients Undergoing Non-curative Surgery.

PubMed

Mimatsu, Kenji; Fukino, Nobutada; Ogasawara, Yasuo; Saino, Yoko; Oida, Takatsugu

2017-08-01

The present study aimed to compare the utility of various inflammatory marker- and nutritional status-based prognostic factors, including many previous established prognostic factors, for predicting the prognosis of stage IV gastric cancer patients undergoing non-curative surgery. A total of 33 patients with stage IV gastric cancer who had undergone palliative gastrectomy and gastrojejunostomy were included in the study. Univariate and multivariate analyses were performed to evaluate the relationships between the mGPS, PNI, NLR, PLR, the CONUT, various clinicopathological factors and cancer-specific survival (CS). Among patients who received non-curative surgery, univariate analysis of CS identified the following significant risk factors: chemotherapy, mGPS and NLR, and multivariate analysis revealed that the mGPS was independently associated with CS. The mGPS was a more useful prognostic factor than the PNI, NLR, PLR and CONUT in patients undergoing non-curative surgery for stage IV gastric cancer. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Treatment-Related Predictive and Prognostic Factors in Trimodality Approach in Stage IIIA/N2 Non-Small Cell Lung Cancer.

PubMed

Jeremić, Branislav; Casas, Francesc; Dubinsky, Pavol; Gomez-Caamano, Antonio; Čihorić, Nikola; Videtic, Gregory; Igrutinovic, Ivan

2018-01-01

While there are no established pretreatment predictive and prognostic factors in patients with stage IIIA/pN2 non-small cell lung cancer (NSCLC) indicating a benefit to surgery as a part of trimodality approach, little is known about treatment-related predictive and prognostic factors in this setting. A literature search was conducted to identify possible treatment-related predictive and prognostic factors for patients for whom trimodality approach was reported on. Overall survival was the primary endpoint of this study. Of 30 identified studies, there were two phase II studies, 5 "prospective" studies, and 23 retrospective studies. No study was found which specifically looked at treatment-related predictive factors of improved outcomes in trimodality treatment. Of potential treatment-related prognostic factors, the least frequently analyzed factors among 30 available studies were overall pathologic stage after preoperative treatment and UICC downstaging. Evaluation of treatment response before surgery and by pathologic tumor stage after induction therapy were analyzed in slightly more than 40% of studies and found not to influence survival. More frequently studied factors-resection status, degree of tumor regression, and pathologic nodal stage after induction therapy as well as the most frequently studied factor, the treatment (in almost 75% studies)-showed no discernible impact on survival, due to conflicting results. Currently, it is impossible to identify any treatment-related predictive or prognostic factors for selecting surgery in the treatment of patients with stage IIIA/pN2 NSCLC.

Nottingham Prognostic Index Plus (NPI+): a modern clinical decision making tool in breast cancer.

PubMed

Rakha, E A; Soria, D; Green, A R; Lemetre, C; Powe, D G; Nolan, C C; Garibaldi, J M; Ball, G; Ellis, I O

2014-04-02

Current management of breast cancer (BC) relies on risk stratification based on well-defined clinicopathologic factors. Global gene expression profiling studies have demonstrated that BC comprises distinct molecular classes with clinical relevance. In this study, we hypothesised that molecular features of BC are a key driver of tumour behaviour and when coupled with a novel and bespoke application of established clinicopathologic prognostic variables can predict both clinical outcome and relevant therapeutic options more accurately than existing methods. In the current study, a comprehensive panel of biomarkers with relevance to BC was applied to a large and well-characterised series of BC, using immunohistochemistry and different multivariate clustering techniques, to identify the key molecular classes. Subsequently, each class was further stratified using a set of well-defined prognostic clinicopathologic variables. These variables were combined in formulae to prognostically stratify different molecular classes, collectively known as the Nottingham Prognostic Index Plus (NPI+). The NPI+ was then used to predict outcome in the different molecular classes. Seven core molecular classes were identified using a selective panel of 10 biomarkers. Incorporation of clinicopathologic variables in a second-stage analysis resulted in identification of distinct prognostic groups within each molecular class (NPI+). Outcome analysis showed that using the bespoke NPI formulae for each biological BC class provides improved patient outcome stratification superior to the traditional NPI. This study provides proof-of-principle evidence for the use of NPI+ in supporting improved individualised clinical decision making.

Prediction of clinical behaviour and treatment for cancers.

PubMed

Futschik, Matthias E; Sullivan, Mike; Reeve, Anthony; Kasabov, Nikola

2003-01-01

Prediction of clinical behaviour and treatment for cancers is based on the integration of clinical and pathological parameters. Recent reports have demonstrated that gene expression profiling provides a powerful new approach for determining disease outcome. If clinical and microarray data each contain independent information then it should be possible to combine these datasets to gain more accurate prognostic information. Here, we have used existing clinical information and microarray data to generate a combined prognostic model for outcome prediction for diffuse large B-cell lymphoma (DLBCL). A prediction accuracy of 87.5% was achieved. This constitutes a significant improvement compared to the previously most accurate prognostic model with an accuracy of 77.6%. The model introduced here may be generally applicable to the combination of various types of molecular and clinical data for improving medical decision support systems and individualising patient care.

Variations in institutional infrastructure, physician specialization and experience, and outcome in ovarian cancer: a systematic review.

PubMed

du Bois, Andreas; Rochon, Justine; Pfisterer, Jacobus; Hoskins, William J

2009-02-01

Ovarian cancer outcome varies among different institutions, regions, and countries. This systematic review summarizes the available data evaluating the impact of different physician and hospital characteristics on outcome in ovarian cancer patients. A MEDLINE database search for pertinent publications was conducted and reference lists of each relevant article were screened. Experts in the field were contacted. Selected studies assessed the relationship between physician and/or hospital specialty or volume and at least one of the outcomes of interest. The primary outcome was survival. Additional parameters included surgical outcome (debulking), completeness of staging, and quality of chemotherapy. The authors independently reviewed each article and applied the inclusion/exclusion criteria. The quality of each study was assessed by focusing on strategies to control for important prognostic factors. Forty-four articles met inclusion criteria. Discipline and sub-specialization of the primary treating physician were identified as the most important variable associated with superior outcome. Evidence showing a beneficial impact of institutional factors was weaker, but followed the same trend. Hospital volume was hardly related to any outcome parameter. The limited evidence available showed considerable heterogeneity and has to be interpreted cautiously. Better utilization of knowledge about institutional factors and well-established board certifications may improve outcome in ovarian cancer. Patients and primary-care physicians should select gynecologic oncologists for primary treatment in countries with established sub-specialty training. Policymakers, insurance companies, and lay organizations should support development of respective programs.

Effect of the physicochemical parameters of benzimidazole molecules on their retention by a nonpolar sorbent from an aqueous acetonitrile solution

NASA Astrophysics Data System (ADS)

Shafigulin, R. V.; Safonova, I. A.; Bulanova, A. V.

2015-09-01

The effect of the structure of benzimidazoles on their chromatographic retention on octadecyl silica gel from an aqueous acetonitrile eluent was studied. One- and many-parameter correlation equations were obtained by linear regression analysis, and their prognostic potential in determining the retention factors of benzimidazoles under study was analyzed.

Incremental Prognostic Value of Apparent Diffusion Coefficient Histogram Analysis in Head and Neck Squamous Cell Carcinoma.

PubMed

Li, Xiaoxia; Yuan, Ying; Ren, Jiliang; Shi, Yiqian; Tao, Xiaofeng

2018-03-26

We aimed to investigate the incremental prognostic value of apparent diffusion coefficient (ADC) histogram analysis in patients with head and neck squamous cell carcinoma (HNSCC) and integrate it into a multivariate prognostic model. A retrospective review of magnetic resonance imaging findings was conducted in patients with pathologically confirmed HNSCC between June 2012 and December 2015. For each tumor, six histogram parameters were derived: the 10th, 50th, and 90th percentiles of ADC (ADC 10 , ADC 50 , and ADC 90 ); mean ADC values (ADC mean ); kurtosis; and skewness. The clinical variables included age, sex, smoking status, tumor volume, and tumor node metastasis stage. The association of these histogram and clinical variables with overall survival (OS) was determined. Further validation of the histogram parameters as independent biomarkers was performed using multivariate Cox proportional hazard models combined with clinical variables, which was compared to the clinical model. Models were assessed with C index and receiver operating characteristic curve analyses for the 12- and 36-month OS. Ninety-six patients were eligible for analysis. Median follow-up was 877 days (range, 54-1516 days). A total of 29 patients died during follow-up (30%). Patients with higher ADC values (ADC 10  > 0.958 × 10 -3 mm 2 /s, ADC 50  > 1.089 × 10 -3 mm 2 /s, ADC 90  > 1.152 × 10 -3 mm 2 /s, ADC mean  > 1.047 × 10 -3 mm 2 /s) and lower kurtosis (≤0.967) were significant predictors of poor OS (P < .100 for all). After adjusting for sex and tumor node metastasis stage, the ADC 90 and kurtosis are both significant predictors of OS with hazard ratios = 1.00 (95% confidence interval: 1.001-1.004) and 0.58 (95% confidence interval: 0.37-0.90), respectively. By adding the ADC parameters into the clinical model, the C index and diagnostic accuracies for the 12- and 36-month OS showed significant improvement. ADC histogram analysis has incremental prognostic value in patients with HNSCC and increases the performance of a multivariable prognostic model in addition to clinical variables. Copyright © 2018 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

A new Leukemia Prognostic Scoring System for refractory/relapsed adult acute myelogeneous leukaemia patients: a GOELAMS study.

PubMed

Chevallier, P; Labopin, M; Turlure, P; Prebet, T; Pigneux, A; Hunault, M; Filanovsky, K; Cornillet-Lefebvre, P; Luquet, I; Lode, L; Richebourg, S; Blanchet, O; Gachard, N; Vey, N; Ifrah, N; Milpied, N; Harousseau, J-L; Bene, M-C; Mohty, M; Delaunay, J

2011-06-01

A simplified prognostic score is presented based on the multivariate analysis of 138 refractory/relapsed acute myeloid leukaemia (AML) patients (median age 55 years, range: 19-70) receiving a combination of intensive chemotherapy+Gemtuzumab as salvage regimen. Overall, 2-year event-free survival (EFS) and overall survival (OS) were 29±4% and 36±4%, respectively. Disease status (relapse <12 months, including refractory patients), FLT3-ITD-positive status and high-risk cytogenetics were the three strongest independent adverse prognostic factors for OS and EFS in this series. We then defined three subgroups with striking different outcomes at 2 years: no adverse factor (favourable, N=36): OS 58%, EFS 45%; one adverse factor (intermediate, N=54): OS 37%, EFS 31%; two or three adverse factors (poor, N=43): OS 12%, EFS 12% (P<10(-4), P=0.001). This new simplified Leukemia Prognostic Scoring System was then validated on an independent cohort of 111 refractory/relapsed AML patients. This new simplified prognostic score, using three clinical and biological parameters routinely applied, allow to discriminate around two third of the patients who should benefit from a salvage intensive regimen in the setting of refractory/relapsed AML patients. The other one third of the patients should receive investigational therapy.

Requirements Flowdown for Prognostics and Health Management

NASA Technical Reports Server (NTRS)

Goebel, Kai; Saxena, Abhinav; Roychoudhury, Indranil; Celaya, Jose R.; Saha, Bhaskar; Saha, Sankalita

2012-01-01

Prognostics and Health Management (PHM) principles have considerable promise to change the game of lifecycle cost of engineering systems at high safety levels by providing a reliable estimate of future system states. This estimate is a key for planning and decision making in an operational setting. While technology solutions have made considerable advances, the tie-in into the systems engineering process is lagging behind, which delays fielding of PHM-enabled systems. The derivation of specifications from high level requirements for algorithm performance to ensure quality predictions is not well developed. From an engineering perspective some key parameters driving the requirements for prognostics performance include: (1) maximum allowable Probability of Failure (PoF) of the prognostic system to bound the risk of losing an asset, (2) tolerable limits on proactive maintenance to minimize missed opportunity of asset usage, (3) lead time to specify the amount of advanced warning needed for actionable decisions, and (4) required confidence to specify when prognosis is sufficiently good to be used. This paper takes a systems engineering view towards the requirements specification process and presents a method for the flowdown process. A case study based on an electric Unmanned Aerial Vehicle (e-UAV) scenario demonstrates how top level requirements for performance, cost, and safety flow down to the health management level and specify quantitative requirements for prognostic algorithm performance.

Prognostics of Power Electronics, Methods and Validation Experiments

NASA Technical Reports Server (NTRS)

Kulkarni, Chetan S.; Celaya, Jose R.; Biswas, Gautam; Goebel, Kai

2012-01-01

Abstract Failure of electronic devices is a concern for future electric aircrafts that will see an increase of electronics to drive and control safety-critical equipment throughout the aircraft. As a result, investigation of precursors to failure in electronics and prediction of remaining life of electronic components is of key importance. DC-DC power converters are power electronics systems employed typically as sourcing elements for avionics equipment. Current research efforts in prognostics for these power systems focuses on the identification of failure mechanisms and the development of accelerated aging methodologies and systems to accelerate the aging process of test devices, while continuously measuring key electrical and thermal parameters. Preliminary model-based prognostics algorithms have been developed making use of empirical degradation models and physics-inspired degradation model with focus on key components like electrolytic capacitors and power MOSFETs (metal-oxide-semiconductor-field-effect-transistor). This paper presents current results on the development of validation methods for prognostics algorithms of power electrolytic capacitors. Particularly, in the use of accelerated aging systems for algorithm validation. Validation of prognostics algorithms present difficulties in practice due to the lack of run-to-failure experiments in deployed systems. By using accelerated experiments, we circumvent this problem in order to define initial validation activities.

Whole Blood mRNA Expression-Based Prognosis of Metastatic Renal Cell Carcinoma.

PubMed

Giridhar, Karthik V; Sosa, Carlos P; Hillman, David W; Sanhueza, Cristobal; Dalpiaz, Candace L; Costello, Brian A; Quevedo, Fernando J; Pitot, Henry C; Dronca, Roxana S; Ertz, Donna; Cheville, John C; Donkena, Krishna Vanaja; Kohli, Manish

2017-11-03

The Memorial Sloan Kettering Cancer Center (MSKCC) prognostic score is based on clinical parameters. We analyzed whole blood mRNA expression in metastatic clear cell renal cell carcinoma (mCCRCC) patients and compared it to the MSKCC score for predicting overall survival. In a discovery set of 19 patients with mRCC, we performed whole transcriptome RNA sequencing and selected eighteen candidate genes for further evaluation based on associations with overall survival and statistical significance. In an independent validation of set of 47 patients with mCCRCC, transcript expression of the 18 candidate genes were quantified using a customized NanoString probeset. Cox regression multivariate analysis confirmed that two of the candidate genes were significantly associated with overall survival. Higher expression of BAG1 [hazard ratio (HR) of 0.14, p < 0.0001, 95% confidence interval (CI) 0.04-0.36] and NOP56 (HR 0.13, p < 0.0001, 95% CI 0.05-0.34) were associated with better prognosis. A prognostic model incorporating expression of BAG1 and NOP56 into the MSKCC score improved prognostication significantly over a model using the MSKCC prognostic score only ( p < 0.0001). Prognostic value of using whole blood mRNA gene profiling in mCCRCC is feasible and should be prospectively confirmed in larger studies.

Whole Blood mRNA Expression-Based Prognosis of Metastatic Renal Cell Carcinoma

PubMed Central

Sosa, Carlos P.; Hillman, David W.; Sanhueza, Cristobal; Dalpiaz, Candace L.; Costello, Brian A.; Quevedo, Fernando J.; Pitot, Henry C.; Dronca, Roxana S.; Ertz, Donna; Cheville, John C.; Donkena, Krishna Vanaja; Kohli, Manish

2017-01-01

The Memorial Sloan Kettering Cancer Center (MSKCC) prognostic score is based on clinical parameters. We analyzed whole blood mRNA expression in metastatic clear cell renal cell carcinoma (mCCRCC) patients and compared it to the MSKCC score for predicting overall survival. In a discovery set of 19 patients with mRCC, we performed whole transcriptome RNA sequencing and selected eighteen candidate genes for further evaluation based on associations with overall survival and statistical significance. In an independent validation of set of 47 patients with mCCRCC, transcript expression of the 18 candidate genes were quantified using a customized NanoString probeset. Cox regression multivariate analysis confirmed that two of the candidate genes were significantly associated with overall survival. Higher expression of BAG1 [hazard ratio (HR) of 0.14, p < 0.0001, 95% confidence interval (CI) 0.04–0.36] and NOP56 (HR 0.13, p < 0.0001, 95% CI 0.05–0.34) were associated with better prognosis. A prognostic model incorporating expression of BAG1 and NOP56 into the MSKCC score improved prognostication significantly over a model using the MSKCC prognostic score only (p < 0.0001). Prognostic value of using whole blood mRNA gene profiling in mCCRCC is feasible and should be prospectively confirmed in larger studies. PMID:29099775

Predictive value of seven preoperative prognostic scoring systems for spinal metastases.

PubMed

Leithner, Andreas; Radl, Roman; Gruber, Gerald; Hochegger, Markus; Leithner, Katharina; Welkerling, Heike; Rehak, Peter; Windhager, Reinhard

2008-11-01

Predicting prognosis is the key factor in selecting the proper treatment modality for patients with spinal metastases. Therefore, various assessment systems have been designed in order to provide a basis for deciding the course of treatment. Such systems have been proposed by Tokuhashi, Sioutos, Tomita, Van der Linden, and Bauer. The scores differ greatly in the kind of parameters assessed. The aim of this study was to evaluate the prognostic value of each score. Eight parameters were assessed for 69 patients (37 male, 32 female): location, general condition, number of extraspinal bone metastases, number of spinal metastases, visceral metastases, primary tumour, severity of spinal cord palsy, and pathological fracture. Scores according to Tokuhashi (original and revised), Sioutos, Tomita, Van der Linden, and Bauer were assessed as well as a modified Bauer score without scoring for pathologic fracture. Nineteen patients were still alive as of September 2006 with a minimum follow-up of 12 months. All other patients died after a mean period of 17 months after operation. The mean overall survival period was only 3 months for lung cancer, followed by prostate (7 months), kidney (23 months), breast (35 months), and multiple myeloma (51 months). At univariate survival analysis, primary tumour and visceral metastases were significant parameters, while Karnofsky score was only significant in the group including myeloma patients. In multivariate analysis of all seven parameters assessed, primary tumour and visceral metastases were the only significant parameters. Of all seven scoring systems, the original Bauer score and a Bauer score without scoring for pathologic fracture had the best association with survival (P < 0.001). The data of the present study emphasize that the original Bauer score and a modified Bauer score without scoring for pathologic fracture seem to be practicable and highly predictive preoperative scoring systems for patients with spinal metastases. However, decision for or against surgery should never be based alone on a prognostic score but should take symptoms like pain or neurological compromise into account.

The prognostic impact of sex on surgically resected non-small cell lung cancer depends on clinicopathologic characteristics.

PubMed

Sterlacci, William; Tzankov, Alexandar; Veits, Lothar; Oberaigner, Wilhelm; Schmid, Thomas; Hilbe, Wolfgang; Fiegl, Michael

2011-04-01

The increasing incidence of lung cancer in women and their supposed survival advantage over men requires clarification of the significance of sex. Age, stage, histologic features, differentiation grade, and Ki-67 index were assessed in 405 surgically resected non-small cell lung cancers (NSCLCs) using a standardized tissue microarray platform. Women were associated with well/moderate tumor differentiation, a Ki-67 index of 3% or less, and adenocarcinoma histologic features. Female sex predicted increased survival time only by univariate analysis. Stratified by sex, increased survival was noted for women older than 64 years, with a tumor at postsurgical International Union Against Cancer stage I, with adenocarcinoma histologic features, with well- or moderately differentiated tumors, or with a Ki-67 index of 3% or less. Sex is not an independent prognostic parameter for patients with surgically resected NSCLC. Sex-linked differences are associated with other factors, thus simulating a prognostic impact of sex. This study elucidates sex-specific interactions between patient and tumor characteristics, which are pivotal toward improving prognostic accuracy, individualized therapies, and screening efforts.

Cost-Utility of a Prognostic Test Guiding Adjuvant Chemotherapy Decisions in Early-Stage Non-Small Cell Lung Cancer.

PubMed

Stenehjem, David D; Bellows, Brandon K; Yager, Kraig M; Jones, Joshua; Kaldate, Rajesh; Siebert, Uwe; Brixner, Diana I

2016-02-01

A prognostic test was developed to guide adjuvant chemotherapy (ACT) decisions in early-stage non-small cell lung cancer (NSCLC) adenocarcinomas. The objective of this study was to compare the cost-utility of the prognostic test to the current standard of care (SoC) in patients with early-stage NSCLC. Lifetime costs (2014 U.S. dollars) and effectiveness (quality-adjusted life-years [QALYs]) of ACT treatment decisions were examined using a Markov microsimulation model from a U.S. third-party payer perspective. Cancer stage distribution and probability of receiving ACT with the SoC were based on data from an academic cancer center. The probability of receiving ACT with the prognostic test was estimated from a physician survey. Risk classification was based on the 5-year predicted NSCLC-related mortality. Treatment benefit with ACT was based on the prognostic score. Discounting at a 3% annual rate was applied to costs and QALYs. Deterministic one-way and probabilistic sensitivity analyses examined parameter uncertainty. Lifetime costs and effectiveness were $137,403 and 5.45 QALYs with the prognostic test and $127,359 and 5.17 QALYs with the SoC. The resulting incremental cost-effectiveness ratio for the prognostic test versus the SoC was $35,867/QALY gained. One-way sensitivity analyses indicated the model was most sensitive to the utility of patients without recurrence after ACT and the ACT treatment benefit. Probabilistic sensitivity analysis indicated the prognostic test was cost-effective in 65.5% of simulations at a willingness to pay of $50,000/QALY. The study suggests using a prognostic test to guide ACT decisions in early-stage NSCLC is potentially cost-effective compared with using the SoC based on globally accepted willingness-to-pay thresholds. Providing prognostic information to decision makers may help some patients with high-risk early stage non-small cell lung cancer receive appropriate adjuvant chemotherapy while avoiding the associated toxicities and costs in patients with low-risk disease. This study used an economic model to assess the effectiveness and costs associated with using a prognostic test to guide adjuvant chemotherapy decisions compared with the current standard of care in patients with non-small cell lung cancer. When compared with current standard care, the prognostic test was potentially cost effective at commonly accepted thresholds in the U.S. This study can be used to help inform decision makers who are considering using prognostic tests. ©AlphaMed Press.

Serum amyloid A as a prognostic marker in melanoma identified by proteomic profiling.

PubMed

Findeisen, Peter; Zapatka, Marc; Peccerella, Teresa; Matzk, Heike; Neumaier, Michael; Schadendorf, Dirk; Ugurel, Selma

2009-05-01

Currently known prognostic serum biomarkers of melanoma are powerful in metastatic disease, but weak in early-stage patients. This study was aimed to identify new prognostic biomarkers of melanoma by serum mass spectrometry (MS) proteomic profiling, and to validate candidates compared with established markers. Two independent sets of serum samples from 596 melanoma patients were investigated. The first set (stage I = 102; stage IV = 95) was analyzed by matrix assisted laser desorption and ionization time of flight (MALDI TOF) MS for biomarkers differentiating between stage I and IV. In the second set (stage I = 98; stage II = 91; stage III = 87; stage IV = 103), the serum concentrations of the candidate marker serum amyloid A (SAA) and the known biomarkers S100B, lactate dehydrogenase, and C reactive protein (CRP) were measured using immunoassays. MALDI TOF MS revealed a peak at m/z 11.680 differentiating between stage I and IV, which could be identified as SAA. High peak intensities at m/z 11.680 correlated with poor survival. In univariate analysis, SAA was a strong prognostic marker in stage I to III (P = .043) and stage IV (P = .000083) patients. Combination of SAA and CRP increased the prognostic impact to P = .011 in early-stage (I to III) patients. Multivariate analysis revealed sex, stage, tumor load, S100B, SAA, and CRP as independent prognostic factors, with an interaction between SAA and CRP. In stage I to III patients, SAA combined with CRP was superior to S100B in predicting patients' progression-free and overall survival. SAA combined with CRP might be used as prognostic serological biomarkers in early-stage melanoma patients, helping to discriminate low-risk patients from high-risk patients needing adjuvant treatment.

Time to treatment and acute coronary syndromes: bridging the gap in rapid decision making.

PubMed

Peacock, W Frank

2010-01-01

The role of cardiac biomarkers in the diagnosis, risk stratification, and treatment of patients with chest pain and suspected acute coronary syndromes (ACS) has continued to evolve. Although it is clear that troponin (Tn) measurement provides independent prognostic information in patients with suspected ACS, it is less well established that early B-type natriuretic peptide (BNP) measurement provides additional incremental prognostic information above and beyond electrocardiography and Tn measurement. It is useful to identify patients at high risk for adverse events through measurement of Tn and BNP levels so that timely treatment decisions can be made.

Evaluation of breast cancer using intravoxel incoherent motion (IVIM) histogram analysis: comparison with malignant status, histological subtype, and molecular prognostic factors.

PubMed

Cho, Gene Young; Moy, Linda; Kim, Sungheon G; Baete, Steven H; Moccaldi, Melanie; Babb, James S; Sodickson, Daniel K; Sigmund, Eric E

2016-08-01

To examine heterogeneous breast cancer through intravoxel incoherent motion (IVIM) histogram analysis. This HIPAA-compliant, IRB-approved retrospective study included 62 patients (age 48.44 ± 11.14 years, 50 malignant lesions and 12 benign) who underwent contrast-enhanced 3 T breast MRI and diffusion-weighted imaging. Apparent diffusion coefficient (ADC) and IVIM biomarkers of tissue diffusivity (Dt), perfusion fraction (fp), and pseudo-diffusivity (Dp) were calculated using voxel-based analysis for the whole lesion volume. Histogram analysis was performed to quantify tumour heterogeneity. Comparisons were made using Mann-Whitney tests between benign/malignant status, histological subtype, and molecular prognostic factor status while Spearman's rank correlation was used to characterize the association between imaging biomarkers and prognostic factor expression. The average values of the ADC and IVIM biomarkers, Dt and fp, showed significant differences between benign and malignant lesions. Additional significant differences were found in the histogram parameters among tumour subtypes and molecular prognostic factor status. IVIM histogram metrics, particularly fp and Dp, showed significant correlation with hormonal factor expression. Advanced diffusion imaging biomarkers show relationships with molecular prognostic factors and breast cancer malignancy. This analysis reveals novel diagnostic metrics that may explain some of the observed variability in treatment response among breast cancer patients. • Novel IVIM biomarkers characterize heterogeneous breast cancer. • Histogram analysis enables quantification of tumour heterogeneity. • IVIM biomarkers show relationships with breast cancer malignancy and molecular prognostic factors.

[Expression of BAG3 Gene in Acute Myeloid Leukemia and Its Prognostic Value].

PubMed

Zhu, Hua-Yuan; Fu, Yuan; Wu, Wei; Xu, Jia-Dai; Chen, Ting-Mei; Qiao, Chun; Li, Jian-Yong; Liu, Peng

2015-08-01

To investigate the expression of BAG3 gene in acue myeloid leukemia (AML) and its prognostic value. Real-time quantitative RT-PCR was used to detect the expression of BAG3 mRNA in 88 previously untreated AML patients. The corelation of BAG3 expression level with clinical characteristics and known prognostic markers of AML was analyzed. In 88 patients with AML, the expression of BAG3 mRNA in NPMI mutated AML patients was obviously lower than that in NPMI unmutated patients (P = 0.018). The expression level of BAG3 mRNA did not related to clinical parameters, such as age, sex, FAB subtype, WBC count, extra-modullary presentation, and to prognostic factors including cytogenetics, FLT3-ITD, c-kit and CEBPα mutation status (P > 0.05). The expression level of BAG3 had no obvious effect on complete remission (CR) of patients in first treatment. The expression level of BAG3 in non-M3 patients was higher than that in relapsed patients (P = 0.036). The expression level of BAG3 had no effect on overall survival (OS) of patients. The expression level of BAG3 does not correlated with known-prognostic markers of AML, only the expression level of BAG3 in NPM1 mutated patients is lower than that in NPM1 unmutated patients. The expression level of BAG3 has no effect on OS of AML patients, the BAG3 can not be difined as a prognostic marker in AML.

[Cleft lip, alveolar and palate sequelae. Proposal of new alveolar score by the Alveolar Cleft Score (ACS) classification].

PubMed

Molé, C; Simon, E

2015-06-01

The management of cleft lip, alveolar and palate sequelae remains problematic today. To optimize it, we tried to establish a new clinical index for diagnostic and prognostic purposes. Seven tissue indicators, that we consider to be important in the management of alveolar sequelae, are listed by assigning them individual scores. The final score, obtained by adding together the individual scores, can take a low, high or maximum value. We propose a new classification (ACS: Alveolar Cleft Score) that guides the therapeutic team to a prognosis approach, in terms of the recommended surgical and prosthetic reconstruction, the type of medical care required, and the preventive and supportive therapy to establish. Current studies are often only based on a standard radiological evaluation of the alveolar bone height at the cleft site. However, the gingival, the osseous and the cellular areas bordering the alveolar cleft sequelae induce many clinical parameters, which should be reflected in the morphological diagnosis, to better direct the surgical indications and the future prosthetic requirements, and to best maintain successful long term aesthetic and functional results. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Gene Expression-Based Survival Prediction in Lung Adenocarcinoma: A Multi-Site, Blinded Validation Study

PubMed Central

Shedden, Kerby; Taylor, Jeremy M.G.; Enkemann, Steve A.; Tsao, Ming S.; Yeatman, Timothy J.; Gerald, William L.; Eschrich, Steve; Jurisica, Igor; Venkatraman, Seshan E.; Meyerson, Matthew; Kuick, Rork; Dobbin, Kevin K.; Lively, Tracy; Jacobson, James W.; Beer, David G.; Giordano, Thomas J.; Misek, David E.; Chang, Andrew C.; Zhu, Chang Qi; Strumpf, Dan; Hanash, Samir; Shepherd, Francis A.; Ding, Kuyue; Seymour, Lesley; Naoki, Katsuhiko; Pennell, Nathan; Weir, Barbara; Verhaak, Roel; Ladd-Acosta, Christine; Golub, Todd; Gruidl, Mike; Szoke, Janos; Zakowski, Maureen; Rusch, Valerie; Kris, Mark; Viale, Agnes; Motoi, Noriko; Travis, William; Sharma, Anupama

2009-01-01

Although prognostic gene expression signatures for survival in early stage lung cancer have been proposed, for clinical application it is critical to establish their performance across different subject populations and in different laboratories. Here we report a large, training-testing, multi-site blinded validation study to characterize the performance of several prognostic models based on gene expression for 442 lung adenocarcinomas. The hypotheses proposed examined whether microarray measurements of gene expression either alone or combined with basic clinical covariates (stage, age, sex) can be used to predict overall survival in lung cancer subjects. Several models examined produced risk scores that substantially correlated with actual subject outcome. Most methods performed better with clinical data, supporting the combined use of clinical and molecular information when building prognostic models for early stage lung cancer. This study also provides the largest available set of microarray data with extensive pathological and clinical annotation for lung adenocarcinomas. PMID:18641660

Protein electrophoresis as a diagnostic and prognostic tool in raptor medicine.

PubMed

Tatum, L M; Zaias, J; Mealey, B K; Cray, C; Bossart, G D

2000-12-01

Plasma proteins of 139 healthy adult birds of prey from 10 species were separated by electrophoresis to characterize and document normal reference ranges and species-specific electrophoretic patternsand to evaluate the value of this technique for health screening, disease diagnosis, and prognostic indication. Species studied included bald eagle (Haliaeetus leucocephalus), red-tailed hawk (Buteo jamaicensis), barn owl (Tyto alba), great horned owl (Bubo virginianus), turkey vulture (Cathartes aura), Harris' hawk (Parabuteo unicinctus), Stellar's sea eagle (Haliaeetus pelagicus), barred owl (Strix varia), screech owl (Otus asio), and black vulture (Coragyps atratus). Several clinical cases show the diagnostic/therapeutic value of protein electrophoresis in raptors. This study establishes species-specific reference ranges for several birds of prey and discusses the benefit of electrophoresis as a diagnostic technique in health screens, as a diagnostic aid in conjunction with other tests, and as a prognostic indicator in clinical evaluation of raptors.

The importance of histopathological and clinical variables in predicting the evolution of colon cancer.

PubMed

Diculescu, Mircea; Iacob, Răzvan; Iacob, Speranţa; Croitoru, Adina; Becheanu, Gabriel; Popeneciu, Valentin

2002-09-01

It has been a consensus that prognostic factors should always be taken into account before planning treatment in colorectal cancer. A 5 year prospective study was conducted, in order to assess the importance of several histopathological and clinical prognostic variables in the prediction of evolution in colon cancer. Some of the factors included in the analysis are still subject to dispute by different authors. 46 of 53 screened patients qualified to enter the study and underwent a potentially curative resection of the tumor, followed, when necessary, by adjuvant chemotherapy. Univariate and multivariate analyses were carried out in order to identify independent prognostic indicators. The endpoint of the study was considered the recurrence of the tumor or the detection of metastases. 65.2% of the patients had a good evolution during the follow up period. Multivariate survival analysis performed by Cox proportional hazard model identified 3 independent prognostic factors: Dukes stage (p = 0.00002), the grade of differentiation (p = 0.0009) and the weight loss index, representing the weight loss of the patient divided by the number of months when it was actually lost (p = 0.02). Age under 40 years, sex, microscopic aspect of the tumor, tumor location, anemia degree were not identified by our analysis as having prognostic importance. Histopathological factors continue to be the most valuable source of information regarding the possible evolution of patients with colorectal cancer. Individual clinical symptoms or biological parameters such as erytrocyte sedimentation rate or hemoglobin level are of little or no prognostic value. More research is required relating to the impact of a performance status index (which could include also weight loss index) as another reliable prognostic variable.

[Results of surgical treatment in ampullary and pancreatic carcinoma and its prognostic parameters after R0-resection].

PubMed

Ridwelski, K; Meyer, F; Schmidt, U; Lippert, H

2005-08-01

Resection is currently the only established reasonable therapeutic option with curative potential in pancreatic and ampullary carcinoma. The aim of the study was i) to analyze value and results of surgical therapy and ii) to detect the prognostic parameters, which determine significantly higher survival rates. Two-hundred-twenty patients with pancreatic and ampullary carcinoma (mean age, 61.4 years; 104 females/116 males) underwent surgery. Histologic investigation revealed 19 carcinomas of the papilla of Vater and 201 ductal pancreatic carcinomas. In 126 patients, stage IV a or b tumors were found, in addition, stage I (n =26), II (n = 17) and III (n = 51). Survival-rate was determined according to the method by Kaplan/Meier. Survival was compared using log-rank test. Association of several or multiple parameters with survival was tested using Cox model. Hundred-ten patients underwent tumor resection with primary curative intention (50 %): 96 resections of the pancreatic head, 2 total pancreatectomies and 12 left resections of the pancreas. R0-resection was achieved in 94 patients (42.7 %), whereas intervention was classified R1 in 10 and R2 in 6 cases. In addition, 60 palliative interventions (28 gastroenterostomies, 17 biliodigestive anastomoses, 15 anastomoses at both sites) and 50 explorative laparotomies were performed. In 42.3 % of patients, postoperative complications were found, but only 12/220 individuals died (overall letality, 5.4 %). Postoperative letality of curative pancreatic resections was 3.6 % (palliative intervention, 6.7 %; explorative laparotomy, 8.8 %). Five-year survival-rate of carcinoma of the papilla of Vater and pancreatic carcinoma was 73.3 % and 16.2 %, respectively (median survival time was 66.0 and 14.0 months, respectively). Taken together all other interventions, median survival time ranged between 4.0 (palliative intervention) to 10.0 months (R1-resection). No patient survived 5 years. Therefore, the most relevant prognostic factor was R0-resection. In addition, prognosis after successful R0-resection is determined significantly by tumor site, stage of the tumor (according to UICC), T- and N-category. Resection of pancreatic and ampullary carcinoma according to oncological criteria with tumor-free margins can be considered a treatment option with curative intention and potential. Despite relative high postoperative morbidity, only a low mortality rate was observed. The 5-year survival-rate of 16.2 % in ductal pancreatic carcinoma underlines the demand for the development of effective multimodal therapeutic concepts. Interventions with primary palliative intention or resections with microscopically or macroscopically detectable tumor residual in situ lead to no significant or only marginal prolongation of survival time. Such interventions in patients with pancreatic carcinoma are no reasonable treatment alternative. They are of value only for treatment of tumor-associated complications and problems.

Specific prognostic factors for secondary pancreatic infection in severe acute pancreatitis.

PubMed

Armengol-Carrasco, M; Oller, B; Escudero, L E; Roca, J; Gener, J; Rodríguez, N; del Moral, P; Moreno, P

1999-01-01

The aim of the present study was to investigate whether there are specific prognostic factors to predict the development of secondary pancreatic infection (SPI) in severe acute pancreatitis in order to perform a computed tomography-fine needle aspiration with bacteriological sampling at the right moment and confirm the diagnosis. Twenty-five clinical and laboratory parameters were determined sequentially in 150 patients with severe acute pancreatitis (SAP) and univariate, and multivariate regression analyses were done looking for correlation with the development of SPI. Only APACHE II score and C-reactive protein levels were related to the development of SPI in the multivariate analysis. A regression equation was designed using these two parameters, and empiric cut-off points defined the subgroup of patients at high risk of developing secondary pancreatic infection. The results showed that it is possible to predict SPI during SAP allowing bacteriological confirmation and early treatment of this severe condition.

The Glasgow Prognostic Score. An useful tool to predict survival in patients with advanced esophageal squamous cell carcinoma.

PubMed

Henry, Maria Aparecida Coelho de Arruda; Lerco, Mauro Masson; de Oliveira, Walmar Kerche; Guerra, Anderson Roberto; Rodrigues, Maria Aparecida Marchesan

2015-08-01

To evaluate the usefulness of the Glasgow Prognostic Score (GPS) in patients with esophageal carcinoma (EC). A total of 50 patients with EC were analyzed for GPS, nutritional and clinicopathologic parameters. Patients with CRP ≤ 1.0mg/L and albumin ≥ 3.5mg/L were considered as GPS = 0. Patients with only CRP increased or albumin decreased were classified as GPS = 1 and patients with CRP > 1.0mg/L and albumin < 3.5mg/L were considered as GPS = 2. GPS of 0, 1 and 2 were observed in seven, 23 and 20 patients, respectively. A significant inverse relationship was observed between GPS scores and the survival rate. The survival rate was greatest in patients with GPS = 0 and significantly higher than those from patients with GPS = 1 and GPS = 2. Minimum 12-month survival was observed in 71% patients with GPS = 0 and in 30% patients with GPS = 1. None of the patients with GPS = 2 survived for 12 months. A significant relationship between CRP or albumin individually and the survival rate was observed. No significant relationship among nutritional, clinic pathological parameters and survival was found. Glasgow Prognostic Score is an useful tool to predict survival in patients with esophageal carcinoma.

Pre-treatment red blood cell distribution width provides prognostic information in multiple myeloma.

PubMed

Zhou, Di; Xu, Peipei; Peng, Miaoxin; Shao, Xiaoyan; Wang, Miao; Ouyang, Jian; Chen, Bing

2018-06-01

The red blood cell distribution width (RDW), a credible marker for abnormal erythropoiesis, has recently been studied as a prognostic factor in oncology, but its role in multiple myeloma (MM) hasn't been thoroughly investigated. We performed a retrospective study in 162 patients with multiple myeloma. Categorical parameters were analyzed using Pearson chi-squared test. The Mann-Whitney and Wilcoxon tests were used for group comparisons. Comparisons of repeated samples data were analyzed with the general linear model repeated-measures procedure. The Kaplan-Meier product-limit method was used to determine OS and PFS, and the differences were assessed by the log-rank test. High RDW baseline was significantly associated with indexes including haemoglobin, bone marrow plasma cell infiltration, and cytogenetics risk stratification. After chemotherapy, the overall response rate (ORR) decreased as RDW baseline increased. In 24 patients with high RDW baseline, it was revealed RDW value decreased when patients achieved complete remission (CR), but increased when the disease progressed. The normal-RDW baseline group showed both longer overall survival (OS) and progression-free survival (PFS) than the high-RDW baseline group. Our study suggests pre-treatment RDW level is a prognostic factor in MM and should be regarded as an important parameter for assessment of therapeutic efficiency. Copyright © 2018. Published by Elsevier B.V.

ON THE PROGNOSTIC SIGNIFICANCE OF THE ERYTHROCYTE SEDIMENTATION RATE, THE LEUKOCYTE COUNT, THE HEMOGLOBIN VALUE, AND BODY WEIGHT IN IRRADIATED AND NONIRRADIATED CANCER PATIENTS (in German)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hofmann, D.

1962-06-01

Changes in these parameters were followed in 672 women with genital carcinoma during and after radiotherapy to determine whether any of them could be used to predict the eventual success of the treatment. All of these parameters were found to be of prognostic value in the 394 patients with carcinoma of the uterine cervix of grades I, II, and III. Erythrocyte sedimentation rate (ESR) was initially elevated in these patients, and in those without recurrence, irradiation caused a prompt and progressive drop in ESR. It continued to rise after radiotherapy in those who later showed tumor recurrence. Similar changes inmore » leukocyte count were seen in this group, the counts falling and staying down after successful treatment or rising when the treatment failed. An inverse relation with respect to the hemoglobin level and body wt was seen, both values progressively increasing in cases later shown to be cured and falling in those which were not. These relations did not hold or were of less prognostic value in patients with carcinomas of the body of the uterus, ovary, or vulva. However, in general, a gradual continual fall in ESR and a rapid fall in leukocyte count were favorable signs following irradiation. (BBB)« less

Prognostic Value of Quantitative Stress Perfusion Cardiac Magnetic Resonance.

PubMed

Sammut, Eva C; Villa, Adriana D M; Di Giovine, Gabriella; Dancy, Luke; Bosio, Filippo; Gibbs, Thomas; Jeyabraba, Swarna; Schwenke, Susanne; Williams, Steven E; Marber, Michael; Alfakih, Khaled; Ismail, Tevfik F; Razavi, Reza; Chiribiri, Amedeo

2018-05-01

This study sought to evaluate the prognostic usefulness of visual and quantitative perfusion cardiac magnetic resonance (CMR) ischemic burden in an unselected group of patients and to assess the validity of consensus-based ischemic burden thresholds extrapolated from nuclear studies. There are limited data on the prognostic value of assessing myocardial ischemic burden by CMR, and there are none using quantitative perfusion analysis. Patients with suspected coronary artery disease referred for adenosine-stress perfusion CMR were included (n = 395; 70% male; age 58 ± 13 years). The primary endpoint was a composite of cardiovascular death, nonfatal myocardial infarction, aborted sudden death, and revascularization after 90 days. Perfusion scans were assessed visually and with quantitative analysis. Cross-validated Cox regression analysis and net reclassification improvement were used to assess the incremental prognostic value of visual or quantitative perfusion analysis over a baseline clinical model, initially as continuous covariates, then using accepted thresholds of ≥2 segments or ≥10% myocardium. After a median 460 days (interquartile range: 190 to 869 days) follow-up, 52 patients reached the primary endpoint. At 2 years, the addition of ischemic burden was found to increase prognostic value over a baseline model of age, sex, and late gadolinium enhancement (baseline model area under the curve [AUC]: 0.75; visual AUC: 0.84; quantitative AUC: 0.85). Dichotomized quantitative ischemic burden performed better than visual assessment (net reclassification improvement 0.043 vs. 0.003 against baseline model). This study was the first to address the prognostic benefit of quantitative analysis of perfusion CMR and to support the use of consensus-based ischemic burden thresholds by perfusion CMR for prognostic evaluation of patients with suspected coronary artery disease. Quantitative analysis provided incremental prognostic value to visual assessment and established risk factors, potentially representing an important step forward in the translation of quantitative CMR perfusion analysis to the clinical setting. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Prognostic significance of smoking in addition to established risk factors in patients with Dukes B and C colorectal cancer: a retrospective analysis.

PubMed

Diamantis, N; Xynos, I D; Amptulah, S; Karadima, M; Skopelitis, H; Tsavaris, N

2013-01-01

To investigate the prognostic significance of smoking in addition to established risk factors in patients with Dukes stage B and C colorectal cancer (CRC). 291 consecutive non-selected CRC patients were studied retrospectively. Twenty-three variables were examined using a regression statistical model to identify relevant prognostic factors related to disease free survival (DFS) and overall survival (OS). On multivariate analysis DFS was found to be negatively affected in patients with a smoking history of ≤10 pack-years vs. non-smokers (p<0.016). Additionally, performance status (PS)<90 (p<0.001), Dukes stage C (p<0.001) and elevated tumor markers (p<0.001) at the time of diagnosis were found to adversely affect DFS. Smoking also had a significant association with relapse. Patients with a smoking history of ≤10 pack-years had 2.45 (p<0.018) higher risk of recurrence compared to patients with no smoking history. OS was influenced by Karnofsky performance status (PS), Dukes stage, and elevated tumor markers. In particular patients with PS< 90 had a 4.69-fold higher risk of death (p<0.001) than patients with better PS. Stage C disease was associated with 2.27-fold higher risk of death (p<0.001) than stage B disease, and patients with elevated tumor markers at the time of diagnosis had 2.74-fold higher risk of death (p<0.014) when compared to those whose tumor markers were normal at presentation. Our study associates smoking and relapse incidence in non-clinical- trial CRC patients and reiterates the prognostic significance of PS, stage and tumor markers at the time of diagnosis.

Serum Chloride and Sodium Interplay in Patients With Acute Myocardial Infarction and Heart Failure With Reduced Ejection Fraction: An Analysis From the High-Risk Myocardial Infarction Database Initiative.

PubMed

Ferreira, João Pedro; Girerd, Nicolas; Duarte, Kevin; Coiro, Stefano; McMurray, John J V; Dargie, Henry J; Pitt, Bertram; Dickstein, Kenneth; Testani, Jeffrey M; Zannad, Faiez; Rossignol, Patrick

2017-02-01

Serum chloride levels were recently found to be independently associated with mortality in heart failure (HF). We investigated the relationship between serum chloride and clinical outcomes in 7195 subjects with acute myocardial infarction complicated by reduced left ventricular function and HF. The studied outcomes were all-cause mortality, cardiovascular mortality, and hospitalization for HF. Both chloride and sodium had a nonlinear association with the studied outcomes (P<0.05 for linearity). Patients in the lowest chloride tertile (chloride ≤100) were older, had more comorbidities, and had lower sodium levels (P<0.05 for all). Serum chloride showed a significant interaction with sodium with regard to all studied outcomes (P for interaction <0.05 for all). The lowest chloride tertile (≤100 mmol/L) was associated with increased mortality rates in the context of lower sodium (≤138 mmol/L; adjusted hazard ratio [95% confidence interval] for all-cause mortality=1.42 (1.14-1.77); P=0.002), whereas in the context of higher sodium levels (>141 mmol/L), the association with mortality was lost. Spline-transformed chloride and its interaction with sodium did not add significant prognostic information on top of other well-established prognostic variables (P>0.05 for all outcomes). In post-myocardial infarction with systolic dysfunction and HF, low serum chloride was associated with mortality (but not hospitalization for HF) in the setting of lower sodium. Overall, chloride and its interaction with sodium did not add clinically relevant prognostic information on top of other well-established prognostic variables. Taken together, these data support an integrated and critical consideration of chloride and sodium interplay. © 2017 American Heart Association, Inc.

CD56‐positive haematological neoplasms of the skin: a multicentre study of the Cutaneous Lymphoma Project Group of the European Organisation for Research and Treatment of Cancer

PubMed Central

Assaf, Chalid; Gellrich, Sylke; Whittaker, Sean; Robson, Alistair; Cerroni, Lorenzo; Massone, Cesare; Kerl, Helmut; Rose, Christian; Chott, Andreas; Chimenti, Sergio; Hallermann, Christian; Petrella, Tony; Wechsler, Janine; Bagot, Martine; Hummel, Michael; Bullani‐Kerl, Katrin; Bekkenk, Marcel W; Kempf, Werner; Meijer, Chris J L M; Willemze, Rein; Sterry, Wolfram

2007-01-01

Background Cutaneous lymphomas expressing CD56, a neural cell adhesion molecule, are characterised in most cases by a highly aggressive clinical course and a poor prognosis. However, prognostic subsets within the CD56+ group have been difficult to identify due to the lack of uniform clinicopathological and immunophenotypical criteria. Methods A multicentre study was conducted by the Cutaneous Lymphoma Task Force of the European Organisation for Research and Treatment of Cancer to define prognostic parameters and establish diagnostic and therapeutic guidelines for CD56+ haematological neoplasms presenting primarily in the skin. Results Four different subtypes of lymphoproliferations with CD56 expression were identified: (1) haematodermic neoplasm; (2) skin infiltration as the first manifestation of CD56+ acute myeloid leukaemia; (3) nasal‐type extranodal natural killer/T‐cell lymphoma; and (4) “classical” cases of cutaneous T‐cell lymphoma (CTCL) with co‐expression of the CD56 molecule. Patients in the first three groups had a poor outcome (93% died) with a median survival rate of 11 months (95% CI 2–72 months), whereas all patients with CD56+ CTCL were alive at the last follow‐up. Conclusion Results show that CD56+ cutaneous lymphoproliferative disorders, with the exception of CD56+ CTCL have a very poor prognosis. It is therefore clinically important to separate CD56+ CTCL from the remaining CD56+ haematological disorders. PMID:17018683

Blunted postprandial reaction of portal venous flow in chronic liver disease, assessed with duplex Doppler: significance for prognosis.

PubMed

de Vries, P J; de Hooge, P; Hoekstra, J B; van Hattum, J

1994-12-01

To establish the effects of a meal on portal venous flow and the prognostic value of this parameter, 46 patients with chronic liver disease and 28 healthy subjects were examined with duplex Doppler before and after a meal. The measurements were completed in 40 patients and 21 healthy subjects. Postprandial portal venous diameter, blood velocity and quantitative flow were measured for 60 min. Mean baseline values were: 11.4 mm versus 10.2 mm (p = 0.019), 10.8 cm.s-1 versus 13.4 cm.s-1 (p = 0.015) and 668 ml.min-1 versus 646 ml.min-1 (p = 0.7) respectively. Spleen size was 15.0 cm versus 10.6 cm (p = 0.0001) respectively. Postprandial diameter, velocity and flow increased significantly in patients and controls (p = 0.0001 for all). Mean postprandial flow could best be described by a polynomial equation with a parabolic curve. Patients' curves were more blunted than controls', with significantly different regression constants (p = 0.025 and p = 0.029). All subjects were followed up for survival and variceal haemorrhage. The mean follow-up time was 47 months. Early maximum postprandial velocity (p = 0.041) and large spleen size (p = 0.002) were significantly related to an unfavourable prognosis for survival. Early maximum velocity was also related to increased variceal haemorrhage. This study shows that postprandial portal venous flow is blunted in patients with chronic liver disease. Postprandial portal venous flow may have prognostic significance.

Prognostic marker for liver disease due to alpha1-antitrypsin deficiency.

PubMed

Pferdmenges, D C; Baumann, U; Müller-Heine, A; Framke, T; Pfister, E-D

2013-09-01

Only some Alpha1-antitrypsin deficiency (A1ATD) PiZZ patients develop liver cirrhosis and portal hypertension. Aim of the study was to investigate the course of liver disease associated with PiZZ A1ATD and to determine prognostic factors. We retrospectively reviewed the clinical and laboratory data of all PiZZ children up to 18 years of age admitted to our centre since 1978. 53 patients (age at first visit 2 days to 12 years) met our criteria. The children were divided into 2 groups: group 1 'bad prognosis', meaning the patients which were on the waiting list for liver transplantation (LTx), had a liver transplantation or had died, and group 2 'good prognosis', containing the patients they were living with their own liver. We analysed family history including smoking, gestational age, maternal age at delivery, date of birth, sex, neonatal history, breast-feeding, symptoms at presentation, clinical and laboratory data and date of LTx and/or death. Various anamnesis parameters such as manifestation of neonatal cholestasis showed no prognostic significance. In contrast the laboratory parameters thrombocytes (p=0.008), bilirubin (p<0.001), prothrombin time (p<0.001), choline-sterase (p<0.001), gamma-GT (p=0.001) and GOT (p=0.002) showed a correlation with a liver transplantation and/or death. Prognosis is difficult to determine at an early stage of this disease, but various laboratory parameters can help to predict an outcome. Therefore a regular follow-up is necessary for the children. © Georg Thieme Verlag KG Stuttgart · New York.

Relationship between p53 dysfunction, CD38 expression, and IgV(H) mutation in chronic lymphocytic leukemia.

PubMed

Lin, Ke; Sherrington, Paul D; Dennis, Michael; Matrai, Zoltan; Cawley, John C; Pettitt, Andrew R

2002-08-15

Established adverse prognostic factors in chronic lymphocytic leukemia (CLL) include CD38 expression, relative lack of IgV(H) mutation, and defects of the TP53 gene. However, disruption of the p53 pathway can occur through mechanisms other than TP53 mutation, and we have recently developed a simple screening test that detects p53 dysfunction due to mutation of the genes encoding either p53 or ATM, a kinase that regulates p53. The present study was conducted to examine the predictive value of this test and to establish the relationship between p53 dysfunction, CD38 expression, and IgV(H) mutation. CLL cells from 71 patients were examined for IgV(H) mutation, CD38 expression, and p53 dysfunction (detected as an impaired p53/p21 response to ionizing radiation). Survival data obtained from 69 patients were analyzed according to each of these parameters. Relative lack of IgV(H) mutation (less than 5%; n = 45), CD38 positivity (antigen expressed on more than 20% of malignant cells; n = 19), and p53 dysfunction (n = 19) were independently confirmed as adverse prognostic factors. Intriguingly, all p53-dysfunctional patients and all but one of the CD38(+) patients had less [corrected] than 5% IgV(H) mutation. Moreover, patients with p53 dysfunction and/or CD38 positivity (n = 31) accounted for the short survival of the less mutated group. These findings indicate that the poor outcome associated with having less than 5% IgV(H) mutation may be due to the overrepresentation of high-risk patients with p53 dysfunction and/or CD38 positivity within this group, and that CD38(-) patients with functionally intact p53 may have a prolonged survival regardless of the extent of IgV(H) mutation.

Normal standards for computer-ECG programs for prognostically and diagnostically important ECG variables derived from a large ethnically diverse female cohort: the Women's Health Initiative (WHI).

PubMed

Rautaharju, Pentti M; Zhang, Zhu-ming; Gregg, Richard E; Haisty, Wesley K; Z Vitolins, Mara; Curtis, Anne B; Warren, James; Horaĉek, Milan B; Zhou, Sophia H; Soliman, Elsayed Z

2013-01-01

Substantial new information has emerged recently about the prognostic value for a variety of new ECG variables. The objective of the present study was to establish reference standards for these novel risk predictors in a large, ethnically diverse cohort of healthy women from the Women's Health Initiative (WHI) study. The study population consisted of 36,299 healthy women. Racial differences in rate-adjusted QT end (QT(ea)) and QT peak (QT(pa)) intervals as linear functions of RR were small, leading to the conclusion that 450 and 390 ms are applicable as thresholds for prolonged and shortened QT(ea) and similarly, 365 and 295 ms for prolonged and shortened QT(pa), respectively. As a threshold for increased dispersion of global repolarization (T(peak)T(end) interval), 110 ms was established for white and Hispanic women and 120 ms for African-American and Asian women. ST elevation and depression values for the monitoring leads of each person with limb electrodes at Mason-Likar positions and chest leads at level of V1 and V2 were first computed from standard leads using lead transformation coefficients derived from 892 body surface maps, and subsequently normal standards were determined for the monitoring leads, including vessel-specific bipolar left anterior descending, left circumflex artery and right coronary artery leads. The results support the choice 150 μV as a tentative threshold for abnormal ST-onset elevation for all monitoring leads. Body mass index (BMI) had a profound effect on Cornell voltage and Sokolow-Lyon voltage in all racial groups and their utility for left ventricular hypertrophy classification remains open. Common thresholds for all racial groups are applicable for QT(ea), and QT(pa) intervals and ST elevation. Race-specific normal standards are required for many other ECG parameters. Copyright © 2013 Elsevier Inc. All rights reserved.

P21, COX-2, and E-cadherin are potential prognostic factors for esophageal squamous cell carcinoma.

PubMed

Lin, Yao; Shen, Lu-Yan; Fu, Hao; Dong, Bin; Yang, He-Li; Yan, Wan-Pu; Kang, Xiao-Zheng; Dai, Liang; Zhou, Hai-Tao; Yang, Yong-Bo; Liang, Zhen; Chen, Ke-Neng

2017-02-01

Much research effort has been devoted to identifying prognostic factors for esophageal squamous cell carcinoma (ESCC) by immunohistochemistry; however, no conclusive findings have been reached thus far. We hypothesized that certain molecules identified in previous studies might serve as useful prognostic markers for ESCC. Therefore, the aim of the current study was to validate the most relevant markers showing potential for ESCC prognosis in our prospective esophageal cancer database. A literature search was performed using the PubMed database for papers published between 1980 and 2015 using the following key words: 'esophageal cancer,' 'prognosis,' and 'immunohistochemistry.' Literature selection criteria were established to identify the most widely studied markers, and we further validated the selected markers in a cohort from our single-surgeon team, including 153 esophageal cancer patients treated from 2000 to 2010. A total of 1799 articles were identified, 82 of which met the selection criteria. Twelve markers were found to be the most widely studied, and the validation results indicated that only P21, COX-2, and E-cadherin were independent prognostic factors for ESCC patients in this series. The systemic review and cohort validation suggest that P21, COX-2, and E-cadherin are potential prognostic factors for ESCC, paving the way for more targeted prospective validation in the future. © 2016 International Society for Diseases of the Esophagus.

A framework for quantifying net benefits of alternative prognostic models.

PubMed

Rapsomaniki, Eleni; White, Ian R; Wood, Angela M; Thompson, Simon G

2012-01-30

New prognostic models are traditionally evaluated using measures of discrimination and risk reclassification, but these do not take full account of the clinical and health economic context. We propose a framework for comparing prognostic models by quantifying the public health impact (net benefit) of the treatment decisions they support, assuming a set of predetermined clinical treatment guidelines. The change in net benefit is more clinically interpretable than changes in traditional measures and can be used in full health economic evaluations of prognostic models used for screening and allocating risk reduction interventions. We extend previous work in this area by quantifying net benefits in life years, thus linking prognostic performance to health economic measures; by taking full account of the occurrence of events over time; and by considering estimation and cross-validation in a multiple-study setting. The method is illustrated in the context of cardiovascular disease risk prediction using an individual participant data meta-analysis. We estimate the number of cardiovascular-disease-free life years gained when statin treatment is allocated based on a risk prediction model with five established risk factors instead of a model with just age, gender and region. We explore methodological issues associated with the multistudy design and show that cost-effectiveness comparisons based on the proposed methodology are robust against a range of modelling assumptions, including adjusting for competing risks. Copyright © 2011 John Wiley & Sons, Ltd.

A framework for quantifying net benefits of alternative prognostic models‡

PubMed Central

Rapsomaniki, Eleni; White, Ian R; Wood, Angela M; Thompson, Simon G

2012-01-01

New prognostic models are traditionally evaluated using measures of discrimination and risk reclassification, but these do not take full account of the clinical and health economic context. We propose a framework for comparing prognostic models by quantifying the public health impact (net benefit) of the treatment decisions they support, assuming a set of predetermined clinical treatment guidelines. The change in net benefit is more clinically interpretable than changes in traditional measures and can be used in full health economic evaluations of prognostic models used for screening and allocating risk reduction interventions. We extend previous work in this area by quantifying net benefits in life years, thus linking prognostic performance to health economic measures; by taking full account of the occurrence of events over time; and by considering estimation and cross-validation in a multiple-study setting. The method is illustrated in the context of cardiovascular disease risk prediction using an individual participant data meta-analysis. We estimate the number of cardiovascular-disease-free life years gained when statin treatment is allocated based on a risk prediction model with five established risk factors instead of a model with just age, gender and region. We explore methodological issues associated with the multistudy design and show that cost-effectiveness comparisons based on the proposed methodology are robust against a range of modelling assumptions, including adjusting for competing risks. Copyright © 2011 John Wiley & Sons, Ltd. PMID:21905066

Prognostic modelling options for remaining useful life estimation by industry

NASA Astrophysics Data System (ADS)

Sikorska, J. Z.; Hodkiewicz, M.; Ma, L.

2011-07-01

Over recent years a significant amount of research has been undertaken to develop prognostic models that can be used to predict the remaining useful life of engineering assets. Implementations by industry have only had limited success. By design, models are subject to specific assumptions and approximations, some of which are mathematical, while others relate to practical implementation issues such as the amount of data required to validate and verify a proposed model. Therefore, appropriate model selection for successful practical implementation requires not only a mathematical understanding of each model type, but also an appreciation of how a particular business intends to utilise a model and its outputs. This paper discusses business issues that need to be considered when selecting an appropriate modelling approach for trial. It also presents classification tables and process flow diagrams to assist industry and research personnel select appropriate prognostic models for predicting the remaining useful life of engineering assets within their specific business environment. The paper then explores the strengths and weaknesses of the main prognostics model classes to establish what makes them better suited to certain applications than to others and summarises how each have been applied to engineering prognostics. Consequently, this paper should provide a starting point for young researchers first considering options for remaining useful life prediction. The models described in this paper are Knowledge-based (expert and fuzzy), Life expectancy (stochastic and statistical), Artificial Neural Networks, and Physical models.

Cytogenetic prognostication within medulloblastoma subgroups.

PubMed

Shih, David J H; Northcott, Paul A; Remke, Marc; Korshunov, Andrey; Ramaswamy, Vijay; Kool, Marcel; Luu, Betty; Yao, Yuan; Wang, Xin; Dubuc, Adrian M; Garzia, Livia; Peacock, John; Mack, Stephen C; Wu, Xiaochong; Rolider, Adi; Morrissy, A Sorana; Cavalli, Florence M G; Jones, David T W; Zitterbart, Karel; Faria, Claudia C; Schüller, Ulrich; Kren, Leos; Kumabe, Toshihiro; Tominaga, Teiji; Shin Ra, Young; Garami, Miklós; Hauser, Peter; Chan, Jennifer A; Robinson, Shenandoah; Bognár, László; Klekner, Almos; Saad, Ali G; Liau, Linda M; Albrecht, Steffen; Fontebasso, Adam; Cinalli, Giuseppe; De Antonellis, Pasqualino; Zollo, Massimo; Cooper, Michael K; Thompson, Reid C; Bailey, Simon; Lindsey, Janet C; Di Rocco, Concezio; Massimi, Luca; Michiels, Erna M C; Scherer, Stephen W; Phillips, Joanna J; Gupta, Nalin; Fan, Xing; Muraszko, Karin M; Vibhakar, Rajeev; Eberhart, Charles G; Fouladi, Maryam; Lach, Boleslaw; Jung, Shin; Wechsler-Reya, Robert J; Fèvre-Montange, Michelle; Jouvet, Anne; Jabado, Nada; Pollack, Ian F; Weiss, William A; Lee, Ji-Yeoun; Cho, Byung-Kyu; Kim, Seung-Ki; Wang, Kyu-Chang; Leonard, Jeffrey R; Rubin, Joshua B; de Torres, Carmen; Lavarino, Cinzia; Mora, Jaume; Cho, Yoon-Jae; Tabori, Uri; Olson, James M; Gajjar, Amar; Packer, Roger J; Rutkowski, Stefan; Pomeroy, Scott L; French, Pim J; Kloosterhof, Nanne K; Kros, Johan M; Van Meir, Erwin G; Clifford, Steven C; Bourdeaut, Franck; Delattre, Olivier; Doz, François F; Hawkins, Cynthia E; Malkin, David; Grajkowska, Wieslawa A; Perek-Polnik, Marta; Bouffet, Eric; Rutka, James T; Pfister, Stefan M; Taylor, Michael D

2014-03-20

Medulloblastoma comprises four distinct molecular subgroups: WNT, SHH, Group 3, and Group 4. Current medulloblastoma protocols stratify patients based on clinical features: patient age, metastatic stage, extent of resection, and histologic variant. Stark prognostic and genetic differences among the four subgroups suggest that subgroup-specific molecular biomarkers could improve patient prognostication. Molecular biomarkers were identified from a discovery set of 673 medulloblastomas from 43 cities around the world. Combined risk stratification models were designed based on clinical and cytogenetic biomarkers identified by multivariable Cox proportional hazards analyses. Identified biomarkers were tested using fluorescent in situ hybridization (FISH) on a nonoverlapping medulloblastoma tissue microarray (n = 453), with subsequent validation of the risk stratification models. Subgroup information improves the predictive accuracy of a multivariable survival model compared with clinical biomarkers alone. Most previously published cytogenetic biomarkers are only prognostic within a single medulloblastoma subgroup. Profiling six FISH biomarkers (GLI2, MYC, chromosome 11 [chr11], chr14, 17p, and 17q) on formalin-fixed paraffin-embedded tissues, we can reliably and reproducibly identify very low-risk and very high-risk patients within SHH, Group 3, and Group 4 medulloblastomas. Combining subgroup and cytogenetic biomarkers with established clinical biomarkers substantially improves patient prognostication, even in the context of heterogeneous clinical therapies. The prognostic significance of most molecular biomarkers is restricted to a specific subgroup. We have identified a small panel of cytogenetic biomarkers that reliably identifies very high-risk and very low-risk groups of patients, making it an excellent tool for selecting patients for therapy intensification and therapy de-escalation in future clinical trials.

Cytogenetic Prognostication Within Medulloblastoma Subgroups

PubMed Central

Shih, David J.H.; Northcott, Paul A.; Remke, Marc; Korshunov, Andrey; Ramaswamy, Vijay; Kool, Marcel; Luu, Betty; Yao, Yuan; Wang, Xin; Dubuc, Adrian M.; Garzia, Livia; Peacock, John; Mack, Stephen C.; Wu, Xiaochong; Rolider, Adi; Morrissy, A. Sorana; Cavalli, Florence M.G.; Jones, David T.W.; Zitterbart, Karel; Faria, Claudia C.; Schüller, Ulrich; Kren, Leos; Kumabe, Toshihiro; Tominaga, Teiji; Shin Ra, Young; Garami, Miklós; Hauser, Peter; Chan, Jennifer A.; Robinson, Shenandoah; Bognár, László; Klekner, Almos; Saad, Ali G.; Liau, Linda M.; Albrecht, Steffen; Fontebasso, Adam; Cinalli, Giuseppe; De Antonellis, Pasqualino; Zollo, Massimo; Cooper, Michael K.; Thompson, Reid C.; Bailey, Simon; Lindsey, Janet C.; Di Rocco, Concezio; Massimi, Luca; Michiels, Erna M.C.; Scherer, Stephen W.; Phillips, Joanna J.; Gupta, Nalin; Fan, Xing; Muraszko, Karin M.; Vibhakar, Rajeev; Eberhart, Charles G.; Fouladi, Maryam; Lach, Boleslaw; Jung, Shin; Wechsler-Reya, Robert J.; Fèvre-Montange, Michelle; Jouvet, Anne; Jabado, Nada; Pollack, Ian F.; Weiss, William A.; Lee, Ji-Yeoun; Cho, Byung-Kyu; Kim, Seung-Ki; Wang, Kyu-Chang; Leonard, Jeffrey R.; Rubin, Joshua B.; de Torres, Carmen; Lavarino, Cinzia; Mora, Jaume; Cho, Yoon-Jae; Tabori, Uri; Olson, James M.; Gajjar, Amar; Packer, Roger J.; Rutkowski, Stefan; Pomeroy, Scott L.; French, Pim J.; Kloosterhof, Nanne K.; Kros, Johan M.; Van Meir, Erwin G.; Clifford, Steven C.; Bourdeaut, Franck; Delattre, Olivier; Doz, François F.; Hawkins, Cynthia E.; Malkin, David; Grajkowska, Wieslawa A.; Perek-Polnik, Marta; Bouffet, Eric; Rutka, James T.; Pfister, Stefan M.; Taylor, Michael D.

2014-01-01

Purpose Medulloblastoma comprises four distinct molecular subgroups: WNT, SHH, Group 3, and Group 4. Current medulloblastoma protocols stratify patients based on clinical features: patient age, metastatic stage, extent of resection, and histologic variant. Stark prognostic and genetic differences among the four subgroups suggest that subgroup-specific molecular biomarkers could improve patient prognostication. Patients and Methods Molecular biomarkers were identified from a discovery set of 673 medulloblastomas from 43 cities around the world. Combined risk stratification models were designed based on clinical and cytogenetic biomarkers identified by multivariable Cox proportional hazards analyses. Identified biomarkers were tested using fluorescent in situ hybridization (FISH) on a nonoverlapping medulloblastoma tissue microarray (n = 453), with subsequent validation of the risk stratification models. Results Subgroup information improves the predictive accuracy of a multivariable survival model compared with clinical biomarkers alone. Most previously published cytogenetic biomarkers are only prognostic within a single medulloblastoma subgroup. Profiling six FISH biomarkers (GLI2, MYC, chromosome 11 [chr11], chr14, 17p, and 17q) on formalin-fixed paraffin-embedded tissues, we can reliably and reproducibly identify very low-risk and very high-risk patients within SHH, Group 3, and Group 4 medulloblastomas. Conclusion Combining subgroup and cytogenetic biomarkers with established clinical biomarkers substantially improves patient prognostication, even in the context of heterogeneous clinical therapies. The prognostic significance of most molecular biomarkers is restricted to a specific subgroup. We have identified a small panel of cytogenetic biomarkers that reliably identifies very high-risk and very low-risk groups of patients, making it an excellent tool for selecting patients for therapy intensification and therapy de-escalation in future clinical trials. PMID:24493713

Gastric cancer, nutritional status, and outcome.

PubMed

Liu, Xuechao; Qiu, Haibo; Kong, Pengfei; Zhou, Zhiwei; Sun, Xiaowei

2017-01-01

We aim to investigate the prognostic value of several nutrition-based indices, including the prognostic nutritional index (PNI), performance status, body mass index, serum albumin, and preoperative body weight loss in patients with gastric cancer (GC). We retrospectively analyzed the records of 1,330 consecutive patients with GC undergoing curative surgery between October 2000 and September 2012. The relationship between nutrition-based indices and overall survival (OS) was examined using Kaplan-Meier analysis and Cox regression model. Following multivariate analysis, the PNI and preoperative body weight loss were the only nutritional-based indices independently associated with OS (hazard ratio [HR]: 1.356, 95% confidence interval [CI]: 1.051-1.748, P =0.019; HR: 1.152, 95% CI: 1.014-1.310, P =0.030, retrospectively). In stage-stratified analysis, multivariate analysis revealed that preoperative body weight loss was identified as an independent prognostic factor only in patients with stage III GC (HR: 1.223, 95% CI: 1.065-1.405, P =0.004), while the prognostic significance of PNI was not significant (all P >0.05). In patients with stage III GC, preoperative body weight loss stratified 5-year OS from 41.1% to 26.5%. When stratified by adjuvant chemotherapy, the prognostic significance of preoperative body weight loss was maintained in patients treated with surgery plus adjuvant chemotherapy and in patients treated with surgery alone ( P <0.001; P =0.003). Preoperative body weight loss is an independent prognostic factor for OS in patients with GC, especially in stage III disease. Preoperative body weight loss appears to be a superior predictor of outcome compared with other established nutrition-based indices.

The prognostic value of individual NT-proBNP values in chronic heart failure does not change with advancing age.

PubMed

Frankenstein, L; Clark, A L; Goode, K; Ingle, L; Remppis, A; Schellberg, D; Grabs, F; Nelles, M; Cleland, J G F; Katus, H A; Zugck, C

2009-05-01

It is unclear whether age-related increases in N-terminal pro-brain natriuretic peptide (NT-proBNP) represent a normal physiological process-possibly affecting the prognostic power-of NT-proBNP-or reflect age-related subclinical pathological changes. To determine the effect of age on the short-term prognostic value of NT-proBNP in patients with chronic heart failure (CHF). Prospective observational study with inclusion and matching of consecutive patients aged >65 years (mean (SD) 73.1 (6.0) years) to patients <65 years (53.7 (8.6) years) with respect to NT-proBNP, New York Heart Association stage, sex and aetiology of CHF (final n = 443). University hospital outpatient departments in the UK and Germany. Chronic stable heart failure due to systolic left ventricular dysfunction. None. All-cause mortality. In both age groups, NT-proBNP was a significant univariate predictor of mortality, and independent of age, sex and other established risk markers. The prognostic information given by NT-proBNP was comparable between the two groups, as reflected by the 1-year mortality of 9% in both groups. The prognostic accuracy of NT-proBNP as judged by the area under the receiver operating characteristics curve for the prediction of 1-year mortality was comparable for elderly and younger patients (0.67 vs 0.71; p = 0.09). NT-proBNP reflects disease severity in elderly and younger patients alike. In patients with chronic stable heart failure, the NT-proBNP value carries the same 1-year prognostic information regardless of the age of the patient.

Whole-brain perfusion CT using a toggling table technique to predict final infarct volume in acute ischemic stroke.

PubMed

Schrader, I; Wilk, D; Jansen, O; Riedel, C

2013-09-01

To evaluate how accurately final infarct volume in acute ischemic stroke can be predicted with perfusion CT (PCT) using a 64-MDCT unit and the toggling table technique. Retrospective analysis of 89 patients with acute ischemic stroke who underwent CCT, CT angiography (CTA) and PCT using the "toggling table" technique within the first three hours after symptom onset. In patients with successful thrombolytic therapy (n = 48) and in those without effective thrombolytic therapy (n = 41), the infarct volume and the volume of the penumbra on PCT were compared to the infarct size on follow-up images (CT or MRI) performed within 8 days. The feasibility of complete infarct volume prediction by 8 cm cranio-caudal coverage was evaluated. The correlation between the volume of hypoperfusion on PCT defined by cerebral blood volume reduction and final infarct volume was strongest in patients with successful thrombolytic therapy with underestimation of the definite infarct volume by 8.5 ml on average. The CBV map had the greatest prognostic value. In patients without successful thrombolytic therapy, the final infarct volume was overestimated by 12.1 ml compared to the MTT map on PCT. All infarcts were detected completely. There were no false-positive or false-negative results. Using PCT and the "toggling table" technique in acute stroke patients is helpful for the rapid and accurate quantification of the minimal final infarct and is therefore a prognostic parameter which has to be evaluated in further studies to assess its impact on therapeutic decision. ▶ Using PCT and the “toggling table technique” allows accurate quantification of the infarct core and penumbra. ▶ It is possible to record dynamic perfusion parameters quickly and easily of almost the entire supratentorial brain volume on a 64-slice MDCT unit. ▶ The technique allows identification of those patients who could profit from thrombolytic therapy outside the established time intervals. © Georg Thieme Verlag KG Stuttgart · New York.

Preoperative prognostic value of dynamic contrast-enhanced MRI-derived contrast transfer coefficient and plasma volume in patients with cerebral gliomas.

PubMed

Nguyen, T B; Cron, G O; Mercier, J F; Foottit, C; Torres, C H; Chakraborty, S; Woulfe, J; Jansen, G H; Caudrelier, J M; Sinclair, J; Hogan, M J; Thornhill, R E; Cameron, I G

2015-01-01

The prognostic value of dynamic contrast-enhanced MR imaging-derived plasma volume obtained in tumor and the contrast transfer coefficient has not been well-established in patients with gliomas. We determined whether plasma volume and contrast transfer coefficient in tumor correlated with survival in patients with gliomas in addition to other factors such as age, type of surgery, preoperative Karnofsky score, contrast enhancement, and histopathologic grade. This prospective study included 46 patients with a new pathologically confirmed diagnosis of glioma. The contrast transfer coefficient and plasma volume obtained in tumor maps were calculated directly from the signal-intensity curve without T1 measurements, and values were obtained from multiple small ROIs placed within tumors. Survival curve analysis was performed by dichotomizing patients into groups of high and low contrast transfer coefficient and plasma volume. Univariate analysis was performed by using dynamic contrast-enhanced parameters and clinical factors. Factors that were significant on univariate analysis were entered into multivariate analysis. For all patients with gliomas, survival was worse for groups of patients with high contrast transfer coefficient and plasma volume obtained in tumor (P < .05). In subgroups of high- and low-grade gliomas, survival was worse for groups of patients with high contrast transfer coefficient and plasma volume obtained in tumor (P < .05). Univariate analysis showed that factors associated with lower survival were age older than 50 years, low Karnofsky score, biopsy-only versus resection, marked contrast enhancement versus no/mild enhancement, high contrast transfer coefficient, and high plasma volume obtained in tumor (P < .05). In multivariate analysis, a low Karnofsky score, biopsy versus resection in combination with marked contrast enhancement, and a high contrast transfer coefficient were associated with lower survival rates (P < .05). In patients with glioma, those with a high contrast transfer coefficient have lower survival than those with low parameters. © 2015 by American Journal of Neuroradiology.

Value of quantitative MRI parameters in predicting and evaluating clinical outcome in conservatively treated patients with chronic midportion Achilles tendinopathy: A prospective study.

PubMed

Tsehaie, J; Poot, D H J; Oei, E H G; Verhaar, J A N; de Vos, R J

2017-07-01

To evaluate whether baseline MRI parameters provide prognostic value for clinical outcome, and to study correlation between MRI parameters and clinical outcome. Observational prospective cohort study. Patients with chronic midportion Achilles tendinopathy were included and performed a 16-week eccentric calf-muscle exercise program. Outcome measurements were the validated Victorian Institute of Sports Assessment-Achilles (VISA-A) questionnaire and MRI parameters at baseline and after 24 weeks. The following MRI parameters were assessed: tendon volume (Volume), tendon maximum cross-sectional area (CSA), tendon maximum anterior-posterior diameter (AP), and signal intensity (SI). Intra-class correlation coefficients (ICCs) and minimum detectable changes (MDCs) for each parameter were established in a reliability analysis. Twenty-five patients were included and complete follow-up was achieved in 20 patients. The average VISA-A scores increased significantly with 12.3 points (27.6%). The reliability was fair-good for all MRI-parameters with ICCs>0.50. Average tendon volume and CSA decreased significantly with 0.28cm 3 (5.2%) and 4.52mm 2 (4.6%) respectively. Other MRI parameters did not change significantly. None of the baseline MRI parameters were univariately associated with VISA-A change after 24 weeks. MRI SI increase over 24 weeks was positively correlated with the VISA-A score improvement (B=0.7, R 2 =0.490, p=0.02). Tendon volume and CSA decreased significantly after 24 weeks of conservative treatment. As these differences were within the MDC limits, they could be a result of a measurement error. Furthermore, MRI parameters at baseline did not predict the change in symptoms, and therefore have no added value in providing a prognosis in daily clinical practice. Copyright © 2017 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Serum soluble E-cadherin is a potential prognostic marker in esophageal squamous cell carcinoma.

PubMed

Chung, Y; Law, S; Kwong, D L W; Luk, J M

2011-01-01

E-cadherin is a well-documented tumor suppressor with downregulated expression in many cancer types. Upon proteolytic cleavage, a soluble form of 80-kDa degradation fragment, known as soluble E-cadherin (s-Ecad), is present in circulation; its level in sera of cancer patients is significantly associated with metastasis, recurrence, and prognosis in some malignancies. The present study investigated the association of s-Ecad with clinicopathological characteristics of patients with esophageal squamous cell carcinoma (ESCC) and its prognostic significance. A cohort of 97 patients who underwent surgery alone (n= 56) or neoadjuvant chemoradiation therapy and surgery (CRT) (n= 41) was recruited for this study. Serum samples were collected at operation (surgery group) and pre- and post-CRT treatment (CRT group) for measurement of s-Ecad protein by enzyme linked immunosorbent assay. Serum s-Ecad levels were correlated with clinicopathological parameters as well as survival. Univariate analysis showed no significant relationship between serum s-Ecad level and clinicopathological parameters for all sets of samples. Survival analysis showed that in patients who had surgical resection only, those with s-Ecad levels equal to or below the median value survived significantly longer than those with levels above the median (median survival 25.6 vs. 14.1 months, P= 0.012). Multivariate analysis showed that pathological N stage, M stage, R category, and serum s-Ecad level were significant independent prognostic factors for ESCC patients who underwent surgery only. The hazard ratio for s-Ecad was 1.104 (95% CI: 1.026-1.187) and P= 0.008. Serum s-Ecad was detected in ESCC patients and its potential as an independent prognostic marker requires further investigation. © 2010 Copyright the Authors. Journal compilation © 2010, Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus.

Prognostic Value of [18F]-Fluoromethylcholine Positron Emission Tomography/Computed Tomography Before Stereotactic Body Radiation Therapy for Oligometastatic Prostate Cancer.

PubMed

Cysouw, Matthijs; Bouman-Wammes, Esther; Hoekstra, Otto; van den Eertwegh, Alfons; Piet, Maartje; van Moorselaar, Jeroen; Boellaard, Ronald; Dahele, Max; Oprea-Lager, Daniela

2018-06-01

To investigate the predictive value of [ 18 F]-fluoromethylcholine positron emission tomography/computed tomography (PET/CT)-derived parameters on progression-free survival (PFS) in oligometastatic prostate cancer patients treated with stereotactic body radiation therapy (SBRT). In [ 18 F]-fluoromethylcholine PET/CT scans of 40 consecutive patients with ≤4 metachronous metastases treated with SBRT we retrospectively measured the number of metastases, standardized uptake values (SUV mean , SUV max , SUV peak ), metabolically active tumor volume (MATV), and total lesion choline uptake. Partial-volume correction was applied using the iterative deconvolution Lucy-Richardson algorithm. Thirty-seven lymph node and 13 bone metastases were treated with SBRT. Thirty-three patients (82.5%) had 1 lesion, 4 (10%) had 2 lesions, and 3 (7.5%) had 3 lesions. After a median follow-up of 32.6 months (interquartile range, 35.5 months), the median PFS was 11.5 months (95% confidence interval 8.4-14.6 months). Having more than a single metastasis was a significant prognostic factor (hazard ratio 2.74; P = .03), and there was a trend in risk of progression for large MATV (hazard ratio 1.86; P = .10). No SUV or total lesion choline uptake was significantly predictive for PFS, regardless of partial-volume correction. All PET semiquantitative parameters were significantly correlated with each other (P ≤ .013). The number of choline-avid metastases was a significant prognostic factor for progression after [ 18 F]-fluormethylcholine PET/CT-guided SBRT for recurrent oligometastatic prostate cancer, and there seemed to be a trend in risk of progression for patients with large MATVs. The lesional level of [ 18 F]-fluoromethylcholine uptake was not prognostic for progression. Copyright © 2018 Elsevier Inc. All rights reserved.

Prevalence and Correlation of Human Papilloma Virus and its Types with Prognostic Markers in Patients with Invasive Ductal Carcinoma of the Breast in Kuwait

PubMed Central

Francis, Issam M.; Al-Ayadhy, Bushra; Al-Awadhi, Shafiqa; Kapila, Kusum; Al-Mulla, Fahd

2013-01-01

Objectives: This study aimed to document the association of human papilloma virus (HPV) and its types in breast carcinoma tissues in Kuwaiti women, and correlate this with known prognostic markers. Methods: The clinicopathological data of archived tissue from 144 cases of invasive ductal breast carcinoma were studied (age, histological grade, size of tumour, lymph node metastases, oestrogen/progesterone receptors and human epidermal growth factor receptor 2 status). HPV frequency was documented using immunohistochemistry (IHC) and chromogenic in-situ hybridisation (CISH). HPV types were documented by CISH using HPV probes. CISH and IHC techniques were compared and HPV correlated with prognostic parameters. Results: The HPV prevalence as determined by CISH and IHC was 51 (35.4%) and 24 (16.7%) cases, respectively. The sensitivity of HPV by IHC was 37.3% and specificity was 94.6%. The sensitivity and specificity of HPV-CISH compared to HPVIHC was statistically significant (P <0.001). HPV-CISH was seen in 51 cases. A combination of HPV 6 and 11, and 16 and 18 was seen in 2 (3.9%) cases, and a combination of HPV 6, 11, 31 and 33 was seen in 7 (13.7%) cases. All three HPV probes: 6 and 11, 16 and 18, as well as 31 and 33 were present in 2 (3.9%) cases. The prevalence of HPVCISH in the Kuwaiti and non-Kuwaiti populations was 27 (52.9%) and 19 (37.2%), respectively. No correlation was observed with the prognostic parameters. Conclusion: The frequency of HPV in breast carcinoma cases in Kuwait was 35.4% (CISH). Of those, 52.9% were Kuwaitis in whom both low- and high-risk HPV types were detected. PMID:24273662

Evaluation of clinical, laboratory and morphologic prognostic factors in colon cancer

PubMed Central

Grande, Michele; Milito, Giovanni; Attinà, Grazia Maria; Cadeddu, Federica; Muzi, Marco Gallinella; Nigro, Casimiro; Rulli, Francesco; Farinon, Attilio Maria

2008-01-01

Background The long-term prognosis of patients with colon cancer is dependent on many factors. To investigate the influence of a series of clinical, laboratory and morphological variables on prognosis of colon carcinoma we conducted a retrospective analysis of our data. Methods Ninety-two patients with colon cancer, who underwent surgical resection between January 1999 and December 2001, were analyzed. On survival analysis, demographics, clinical, laboratory and pathomorphological parameters were tested for their potential prognostic value. Furthermore, univariate and multivariate analysis of the above mentioned data were performed considering the depth of tumour invasion into the bowel wall as independent variable. Results On survival analysis we found that depth of tumour invasion (P < 0.001; F-ratio 2.11), type of operation (P < 0.001; F-ratio 3.51) and CT scanning (P < 0.001; F-ratio 5.21) were predictors of survival. Considering the degree of mural invasion as independent variable, on univariate analysis, we observed that mucorrhea, anismus, hematocrit, WBC count, fibrinogen value and CT scanning were significantly related to the degree of mural invasion of the cancer. On the multivariate analysis, fibrinogen value was the most statistically significant variable (P < 0.001) with the highest F-ratio (F-ratio 5.86). Finally, in the present study, the tumour site was significantly related neither to the survival nor to the mural invasion of the tumour. Conclusion The various clinical, laboratory and patho-morphological parameters showed different prognostic value for colon carcinoma. In the future, preoperative prognostic markers will probably gain relevance in order to make a proper choice between surgery, chemotherapy and radiotherapy. Nevertheless, current data do not provide sufficient evidence for preoperative stratification of high and low risk patients. Further assessments in prospective large studies are warranted. PMID:18778464

Which prognostic indicator should we use for clinical practice in the initial evaluation and follow-up of IIP: should we depend on PFT, HRCT or...what?

PubMed

Caminati, Antonella; Harari, Sergio

2005-12-01

Idiopathic interstitial pneumonias are a group of diffuse, inflammatory and fibrotic disorders of the lung parenchyma that cause restrictive physiology and impair gas exchange. Usual interstitial pneumonia and non-specific interstitial pneumonia comprise the majority of idiopathic interstitial pneumonia cases. Previous studies have identified the histopathologic pattern as the most important baseline factor in determining prognosis. The non-invasive diagnosis of these diseases is sometimes uncertain but histological evaluation is an imperfect gold-standard. In some cases, the biopsy specimen may not be representative of the entire lung. In other cases, there may be differences in interpretation of the histological findings. HRCT has also assumed a greater role in the diagnosis and management of patients with idiopathic interstitial pneumonia. Factors affecting prognosis are discussed controversially. Histological criteria, clinical features, or lung function parameters are not clear prognostic indicators. Increased interstitial abnormalities in the HRCT, parameters indicating restrictive lung function, desaturation at 6MWT and abnormal gas exchange are possible determinants of survival. The prognostic value of pulmonary function trends over time may prove more useful. Longitudinal behavior is a more accurate determinant of outcome than evaluation at a single point in time. It is important to remember that no predictor of survival can ever reliably predict an individual patient's prognosis. Physicians should realize this limitation, and use predictor tools as general prognostic guides, not crystal balls. However, due to the great variability in the natural history of the disease, close monitoring of the patients may be necessary to evaluate the individual course of each patient.

Prognostic pathologic factors in radical cystectomy after neoadjuvant chemotherapy.

PubMed

Brimo, Fadi; Downes, Michelle R; Jamaspishvili, Tamara; Berman, David; Barkan, Guliz A; Athanazio, Daniel; Abro, Schuharazad; Visram, Kash; Yilmaz, Asli; Solanki, Shraddha; Hahn, Elan; Siemens, Robert; Kassouf, Wassim; Trpkov, Kiril

2018-05-18

We undertook a systematic evaluation of the prognostic value of numerous histologic factors in 165 radical cystectomies (RC) of patients with invasive urothelial carcinoma who underwent surgery after neoadjuvant chemotherapy (NAC). Tumor regression grade (TRG) and therapy-related stromal and epithelial changes were also recorded. Locally advanced disease (≥pT2 and/or pN+) was present in 64% of patients, 22% had no evidence of residual carcinoma (pT0+pN0) and 28% had no evidence of residual muscle invasive carcinoma (≤pT1+N0). TRG 1, 2, and 3 were found in 32%, 15%, and 50% of patients, respectively. Histologic variants of UC were reported in 25% of cases. The most common therapy-related stromal change was fibroblastic reaction (78%) and the most common epithelial change in residual UC was smudgy and poorly preserved chromatin (28%). Prominent stromal and epithelial changes were noted in 41% and 5% of RC, respectively. Progression was found in 45% of patients and cancer-related deaths occurred in 30%. Multivariate analysis showed that the only independent prognostic parameters for progression were T stage, N stage, lymphovascular invasion, and the margin status. Similarly, only T stage, N stage, and the margin status correlated with cancer-related deaths. Neither TRG, nor any of the stromal or epithelial-related variables correlated with outcome. We confirm that the traditional and routinely-reported histologic parameters in RC post-NAC remain the most powerful prognosticators of disease course. The significance of TRG in the bladder remains unconfirmed. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Lymph node ratio as a prognostic factor in metastatic cutaneous head and neck squamous cell carcinoma.

PubMed

Vasan, Kartik; Low, Tsu-Hui Hubert; Gupta, Ruta; Ashford, Bruce; Asher, Rebecca; Gao, Kan; Ch'ng, Sydney; Palme, Carsten E; Clark, Jonathan R

2018-05-01

The prognostic impact of the size and number of nodal metastases in head and neck cutaneous squamous cell carcinoma (SCC) is well established. The purpose of this study was to validate the prognostic significance of the lymph node ratio in metastatic head and neck cutaneous SCC. A retrospective review of 326 patients with head and neck cutaneous SCC with parotid and/or cervical nodal metastases was performed. The primary endpoints were overall survival (OS) and disease-free survival (DFS). The minimal-P approach was used to investigate the optimal lymph node ratio threshold. Our data included 77 recurrences and 101 deaths. A lymph node ratio of 6% was a significant predictor of shorter DFS (hazard ratio [HR] 1.62; 95% confidence interval [CI] 1.11-2.38; P = .01) and OS (HR 1.63; 95% CI 1.03-2.58; P = 0.04) on multivariable analysis. The lymph node ratio is an independent prognosticator of survival outcomes in patients presenting with metastatic head and neck cutaneous SCC. A lymph node ratio >6% is a significant threshold to categorize patients into low and high risk. © 2018 Wiley Periodicals, Inc.

Statistical considerations on prognostic models for glioma

PubMed Central

Molinaro, Annette M.; Wrensch, Margaret R.; Jenkins, Robert B.; Eckel-Passow, Jeanette E.

2016-01-01

Given the lack of beneficial treatments in glioma, there is a need for prognostic models for therapeutic decision making and life planning. Recently several studies defining subtypes of glioma have been published. Here, we review the statistical considerations of how to build and validate prognostic models, explain the models presented in the current glioma literature, and discuss advantages and disadvantages of each model. The 3 statistical considerations to establishing clinically useful prognostic models are: study design, model building, and validation. Careful study design helps to ensure that the model is unbiased and generalizable to the population of interest. During model building, a discovery cohort of patients can be used to choose variables, construct models, and estimate prediction performance via internal validation. Via external validation, an independent dataset can assess how well the model performs. It is imperative that published models properly detail the study design and methods for both model building and validation. This provides readers the information necessary to assess the bias in a study, compare other published models, and determine the model's clinical usefulness. As editors, reviewers, and readers of the relevant literature, we should be cognizant of the needed statistical considerations and insist on their use. PMID:26657835

Characterization of KIF11 as a novel prognostic biomarker and therapeutic target for oral cancer.

PubMed

Daigo, Kayo; Takano, Atsushi; Thang, Phung Manh; Yoshitake, Yoshihiro; Shinohara, Masanori; Tohnai, Iwau; Murakami, Yoshinori; Maegawa, Jiro; Daigo, Yataro

2018-01-01

Oral cancer has a high mortality rate, and its incidence is increasing gradually worldwide. As the effectiveness of standard treatments is still limited, the development of new therapeutic strategies is eagerly awaited. Kinesin family member 11 (KIF11) is a motor protein required for establishing a bipolar spindle in cell division. The role of KIF11 in oral cancer is unclear. Therefore, the present study aimed to assess the role of KIF11 in oral cancer and evaluate its role as a prognostic biomarker and therapeutic target for treating oral cancer. Immunohistochemical analysis demonstrated that KIF11 was expressed in 64 of 99 (64.6%) oral cancer tissues but not in healthy oral epithelia. Strong KIF11 expression was significantly associated with poor prognosis among oral cancer patients (P=0.034), and multivariate analysis confirmed its independent prognostic value. In addition, inhibition of KIF11 expression by transfection of siRNAs into oral cancer cells or treatment of cells with a KIF11 inhibitor significantly suppressed cell proliferation, probably through G2/M arrest and subsequent induction of apoptosis. These results suggest that KIF11 could be a potential prognostic biomarker and therapeutic target for oral cancer.

Characterization of KIF11 as a novel prognostic biomarker and therapeutic target for oral cancer

PubMed Central

Daigo, Kayo; Takano, Atsushi; Thang, Phung Manh; Yoshitake, Yoshihiro; Shinohara, Masanori; Tohnai, Iwau; Murakami, Yoshinori; Maegawa, Jiro; Daigo, Yataro

2018-01-01

Oral cancer has a high mortality rate, and its incidence is increasing gradually worldwide. As the effectiveness of standard treatments is still limited, the development of new therapeutic strategies is eagerly awaited. Kinesin family member 11 (KIF11) is a motor protein required for establishing a bipolar spindle in cell division. The role of KIF11 in oral cancer is unclear. Therefore, the present study aimed to assess the role of KIF11 in oral cancer and evaluate its role as a prognostic biomarker and therapeutic target for treating oral cancer. Immunohistochemical analysis demonstrated that KIF11 was expressed in 64 of 99 (64.6%) oral cancer tissues but not in healthy oral epithelia. Strong KIF11 expression was significantly associated with poor prognosis among oral cancer patients (P=0.034), and multivariate analysis confirmed its independent prognostic value. In addition, inhibition of KIF11 expression by transfection of siRNAs into oral cancer cells or treatment of cells with a KIF11 inhibitor significantly suppressed cell proliferation, probably through G2/M arrest and subsequent induction of apoptosis. These results suggest that KIF11 could be a potential prognostic biomarker and therapeutic target for oral cancer. PMID:29115586

Prognostic relevance of proliferation markers (Ki-67, PHH3) within the cross-relation of ERG translocation and androgen receptor expression in prostate cancer.

PubMed

Goltz, Diane; Montani, Matteo; Braun, Martin; Perner, Sven; Wernert, Nicolas; Jung, Klaus; Dietel, Manfred; Stephan, Carsten; Kristiansen, Glen

2015-12-01

We evaluated the prognostic value of the mitosis-associated marker phosphorylated histone H3 (PHH3) and Ki-67 in prostate cancer with respect to ERG status and androgen receptor (AR) expression.PHH3 and Ki-67 expression was immunohistochemically detected and digitally quantitated in a radical prostatectomy cohort (n = 640). The results were correlated to clinicopathological parameters including biochemical recurrence times. Prognostic values of PHH3 and Ki-67 were analysed by Cox regression and Kaplan-Meier statistics.In prostate cancer, mean Ki-67 and PHH3 rates were 3.40% (95%CI 3.16-3.63%) and 0.0152% (95%CI 0.0112-0.0191%), respectively.Ki-67 showed a significant correlation with Gleason scores, pT status, margin status, and AR expression, while PHH3 showed a significant correlation with Gleason scores and pT status. Univariate analyses for biochemical recurrence times demonstrated a significant prognostic value for median Ki-67 rate and for the PHH3 rate of the 90th percentile. Of importance, in patient subgroups stratified according to AR expression and ERG translocation, the prognostic power of proliferation markers PHH3 and Ki-67 was markedly enhanced in ERG translocation negative and high-level AR expressing ERG translocation positive prostate cancers.As expected, the proliferation markers PHH3 and Ki-67 predict adverse outcome of prostate cancer and have a particularly pronounced prognostic value in specific molecular subsets of prostate cancer (ERG- or AR+).

The proliferation marker Ki67, but not neuroendocrine expression, is an independent factor in the prediction of prognosis of primary prostate cancer patients

PubMed Central

Pascale, Mariarosa; Aversa, Cinzia; Barbazza, Renzo; Marongiu, Barbara; Siracusano, Salvatore; Stoffel, Flavio; Sulfaro, Sando; Roggero, Enrico; Stanta, Giorgio

2016-01-01

Abstract Background Neuroendocrine markers, which could indicate for aggressive variants of prostate cancer and Ki67 (a well-known marker in oncology for defining tumor proliferation), have already been associated with clinical outcome in prostate cancer. The aim of this study was to investigate the prognostic value of those markers in primary prostate cancer patients. Patients and methods NSE (neuron specific enolase), ChrA (chromogranin A), Syp (Synaptophysin) and Ki67 staining were performed by immunohistochemistry. Then, the prognostic impact of their expression on overall survival was investigated in 166 primary prostate cancer patients by univariate and multivariate analyses. Results NSE, ChrA, Syp and Ki67 were positive in 50, 45, 54 and 146 out of 166 patients, respectively. In Kaplan-Meier analysis only diffuse NSE staining (negative vs diffuse, p = 0.004) and Ki67 (≤ 10% vs > 10%, p < 0.0001) were significantly associated with overall survival. Ki67 expression, but not NSE, resulted as an independent prognostic factor for overall survival in multivariate analysis. Conclusions A prognostic model incorporating Ki67 expression with clinical-pathological covariates could provide additional prognostic information. Ki67 may thus improve prediction of prostate cancer outcome based on standard clinical-pathological parameters improving prognosis and management of prostate cancer patients. PMID:27679548

Prognostic value of CD66b positive tumor-infiltrating neutrophils in testicular germ cell tumor.

PubMed

Yamada, Yuta; Nakagawa, Tohru; Sugihara, Toru; Horiuchi, Takamasa; Yoshizaki, Uran; Fujimura, Tetsuya; Fukuhara, Hiroshi; Urano, Tomohiko; Takayama, Kenichi; Inoue, Satoshi; Kume, Haruki; Homma, Yukio

2016-11-18

Prognostic value of immune cells is not clear in testicular germ cell tumors (TGCTs). We aimed to investigate the prognostic value of tumor-infiltrating neutrophils in TGCTs. A total of 102 patients who underwent orchiectomy for TGCT were investigated for CD66b positive tumor-infiltrating neutrophils (CD66b + TINs). Immmunostaining for CD66b was performed in 102 sections as described. Clinicopathological parameters as well as cancer specific survival and overall survival were assessed for correlation with CD66b + TIN density. High density group was significantly correlated with tumor diameter ≥ 10 cm, presence of nodal/distant metastasis, S stage, diagnosis of nonseminomatous germ cell tumor (NGCT), and presence of venous invasion (p = 0.0198, p < 0.0001, p = 0.0275, p = 0.0004, and p = 0.0287, respectively). It was also significantly associated with cancer-specific and overall survival (logrank p = 0.0036, and p = 0.0002, respectively). Multivariate analysis showed that increased CD66b + TIN was an independent prognostic factor for overall survival (p = 0.0095). Increased CD66b + TIN was significantly associated with presence of metastasis, S stage, and nonseminomatous germ cell tumor diagnosis. It was also an independent prognostic factor of overall survival in patients with TGCT.

NEDD9, an independent good prognostic factor in intermediate-risk acute myeloid leukemia patients

PubMed Central

Pallarès, Victor; Hoyos, Montserrat; Chillón, M. Carmen; Barragán, Eva; Conde, M. Isabel Prieto; Llop, Marta; Céspedes, María Virtudes; Nomdedeu, Josep F.; Brunet, Salut; Sanz, Miguel Ángel; González-Díaz, Marcos; Sierra, Jorge; Casanova, Isolda; Mangues, Ramon

2017-01-01

Intermediate-risk acute myeloid leukemia (IR-AML) is the largest subgroup of AML patients and is highly heterogeneous. Whereas adverse and favourable risk patients have well-established treatment protocols, IR-AML patients have not. It is, therefore, crucial to find novel factors that stratify this subgroup to implement risk-adapted strategies. The CAS (Crk-associated substrate) adaptor protein family regulates cell proliferation, survival, migration and adhesion. Despite its association with metastatic dissemination and prognosis of different solid tumors, the role of these proteins in hematological malignancies has been scarcely evaluated. Nevertheless, previous work has established an important role for the CAS family members NEDD9 or BCAR1 in the migratory and dissemination capacities of myeloid cells. On this basis, we hypothesized that NEDD9 or BCAR1 expression levels could associate with survival in IR-AML patients and become new prognostic markers. To that purpose, we assessed BCAR1 and NEDD9 gene expression in a cohort of 73 adult AML patients validating the results in an independent cohort (n = 206). We have identified NEDD9, but not BCAR1, as a new a marker for longer overall and disease-free survival, and for lower cumulative incidence of relapse. In summary, NEDD9 gene expression is an independent prognostic factor for favourable prognosis in IR-AML patients. PMID:29100287

Resuspension and redistribution of radionuclides during grassland and forest fires in the Chernobyl exclusion zone: part II. Modeling the transport process.

PubMed

Yoschenko, V I; Kashparov, V A; Levchuk, S E; Glukhovskiy, A S; Khomutinin, Yu V; Protsak, V P; Lundin, S M; Tschiersch, J

2006-01-01

To predict parameters of radionuclide resuspension, transport and deposition during forest and grassland fires, several model modules were developed and adapted. Experimental data of controlled burning of prepared experimental plots in the Chernobyl exclusion zone have been used to evaluate the prognostic power of the models. The predicted trajectories and elevations of the plume match with those visually observed during the fire experiments in the grassland and forest sites. Experimentally determined parameters could be successfully used for the calculation of the initial plume parameters which provide the tools for the description of various fire scenarios and enable prognostic calculations. In summary, the model predicts a release of some per thousand from the radionuclide inventory of the fuel material by the grassland fires. During the forest fire, up to 4% of (137)Cs and (90)Sr and up to 1% of the Pu isotopes can be released from the forest litter according to the model calculations. However, these results depend on the parameters of the fire events. In general, the modeling results are in good accordance with the experimental data. Therefore, the considered models were successfully validated and can be recommended for the assessment of the resuspension and redistribution of radionuclides during grassland and forest fires in contaminated territories.

The evolution of clinical trials for infant acute lymphoblastic leukemia

PubMed Central

Kotecha, R S; Gottardo, N G; Kees, U R; Cole, C H

2014-01-01

Acute lymphoblastic leukemia (ALL) in infants has a significantly inferior outcome in comparison with older children. Despite initial improvements in survival of infants with ALL since establishment of the first pediatric cooperative group ALL trials, the poor outcome has plateaued in recent years. Historically, infants were treated on risk-adapted childhood ALL protocols. These studies were pivotal in identifying the need for infant-specific protocols, delineating prognostic categories and the requirement for a more unified approach between study groups to overcome limitations in accrual because of low incidence. This subsequently led to the development of collaborative infant-specific studies. Landmark outcomes have included the elimination of cranial radiotherapy following the discovery of intrathecal and high-dose systemic therapy as a superior and effective treatment strategy for central nervous system disease prophylaxis, with improved neurodevelopmental outcome. Universal prospective identification of independent adverse prognostic factors, including presence of a mixed lineage leukemia rearrangement and young age, has established the basis for risk stratification within current trials. The infant-specific trials have defined limits to which conventional chemotherapeutic agents can be intensified to optimize the balance between treatment efficacy and toxicity. Despite variations in therapeutic intensity, there has been no recent improvement in survival due to the equilibrium between relapse and toxicity. Ultimately, to improve the outcome for infants with ALL, key areas still to be addressed include identification and adaptation of novel prognostic markers and innovative therapies, establishing the role of hematopoietic stem cell transplantation in first complete remission, treatment strategies for relapsed/refractory disease and monitoring and timely intervention of late effects in survivors. This would be best achieved through a single unified international trial. PMID:24727996

Geriatric assessment and biomarkers in patients with metastatic breast cancer receiving first-line mono-chemotherapy: Results from the randomized phase III PELICAN trial.

PubMed

Honecker, Friedemann; Harbeck, Nadia; Schnabel, Claudia; Wedding, Ulrich; Waldenmaier, Dirk; Saupe, Steffen; Jäger, Elke; Schmidt, Marcus; Kreienberg, Rolf; Müller, Lothar; Otremba, Burkhard; Dorn, Julia; Warm, Mathias; Al-Batran, Salah-Eddin; de Wit, Maike

2018-03-01

To determine predictive/prognostic factors for patients with metastatic breast cancer (MBC) receiving first-line monochemotherapy using biomarker analysis and geriatric assessment (GA). Karnofsky Performance Status (KPS) and GA as clinical parameters, and prognostic inflammatory and nutritional index (PINI), and Glasgow prognostic score (GPS) as biomarkers were analyzed for association with clinical outcome within the randomized phase III PEg-LIposomal Doxorubicin vs. CApecitabin iN MBC (PELICAN) trial of first-line pegylated liposomal doxorubicin (PLD) or capecitabine. Of 210 patients, 38% were >65years old. GA (n=152) classified 74% as fit, 10% as compromised, and 16% as frail. Biomarkers showed no age dependency. In multivariate analysis (n=70) KPS, GA, cumulative illness rating scale-geriatrics (CIRS-G), and GPS were significantly associated with time to progression, and KPS, CIRS-G, and instrumental activities of daily living (IADL) from GA, and PINI showed a significant correlation with overall survival. GA evaluation was feasible. KPS significantly correlated with efficacy outcomes. Items of a GA and biomarkers of inflammation and nutrition may have prognostic significance in patients with MBC. Copyright © 2017 Elsevier Inc. All rights reserved.

Chromosomal aberrations and their prognostic value in a series of 174 untreated patients with Waldenström's macroglobulinemia.

PubMed

Nguyen-Khac, Florence; Lambert, Jerome; Chapiro, Elise; Grelier, Aurore; Mould, Sarah; Barin, Carole; Daudignon, Agnes; Gachard, Nathalie; Struski, Stéphanie; Henry, Catherine; Penther, Dominique; Mossafa, Hossein; Andrieux, Joris; Eclache, Virginie; Bilhou-Nabera, Chrystèle; Luquet, Isabelle; Terre, Christine; Baranger, Laurence; Mugneret, Francine; Chiesa, Jean; Mozziconacci, Marie-Joelle; Callet-Bauchu, Evelyne; Veronese, Lauren; Blons, Hélène; Owen, Roger; Lejeune, Julie; Chevret, Sylvie; Merle-Beral, Hélène; Leblondon, Véronique

2013-04-01

Waldenström's macroglobulinemia is a disease of mature B cells, the genetic basis of which is poorly understood. Few recurrent chromosomal abnormalities have been reported, and their prognostic value is not known. We conducted a prospective cytogenetic study of Waldenström's macroglobulinemia and examined the prognostic value of chromosomal aberrations in an international randomized trial. The main aberrations were 6q deletions (30%), trisomy 18 (15%), 13q deletions (13%), 17p (TP53) deletions (8%), trisomy 4 (8%), and 11q (ATM) deletions (7%). There was a significant association between trisomy of chromosome 4 and trisomy of chromosome 18. Translocations involving the IGH genes were rare (<5%). Deletion of 6q and 11q, and trisomy 4, were significantly associated with adverse clinical and biological parameters. Patients with TP53 deletion had short progression-free survival and short disease-free survival. Although rare (<5%), trisomy 12 was associated with short progression-free survival. In conclusion, the cytogenetic profile of Waldenström's macroglobulinemia appears to differ from that of other B-cell lymphomas. Chromosomal abnormalities may help with diagnosis and prognostication, in conjunction with other clinical and biological characteristics.

Prognostic factors, pathophysiology and novel biomarkers in Crimean-Congo hemorrhagic fever.

PubMed

Akinci, Esragul; Bodur, Hurrem; Sunbul, Mustafa; Leblebicioglu, Hakan

2016-08-01

Crimean-Congo hemorrhagic fever (CCHF) is a geographically widespread tick-borne zoonosis. The clinical spectrum of the illness varies from mild infection to severe disease and death. In severe cases, hemorrhagic manifestations develop, with fatality rates of 4-20%, depending on the geographic region and quality of the health care. Although vast majority of the CCHF cases were reported from Turkey, mortality rate is lower than the other regions, which is 5% on average. Prediction of the clinical course of the disease enables appropriate management planning by the physician and prompt transportation, if needed, of the patient to a tertiary care hospital for an intensive therapy. Thus, predicting the outcome of the disease may avert potential mortality. There are numerous studies investigating the prognostic factors of CCHF in the literature. Majority of them were reported from Turkey and included investigations on clinical and biochemical parameters, severity scoring systems and some novel biomarkers. Somnolence, bleeding, thrombocytopenia, elevated liver enzymes and prolonged bleeding times are the most frequently reported prognostic factors to predict the clinical course of the disease earlier. High viral load seems to be the strongest predictor to make a clinical decision about the patient outcome. The severity scoring systems based on clinically important mortality-related parameters are especially useful for clinicians working in the field to predict the course of the disease and to decide which patient should be referred to a tertiary care hospital for intensive care. In the light of the pathophysiological characteristics of CCHF, some new biomarkers of prognosis including cytokines, soluble adhesion molecules, genetic polymorphisms and coagulopathy parameters were also investigated. However most of these tests are not available to clinicians and they were obtained mostly for research purposes. In spite of the various studies about prognostic factors, they have several inherent limitations, including large variability in the results and confusing data that are not useful for clinicians in routine practice. In this paper, the results of diverse studies of the prediction of the prognosis in CCHF based on epidemiological, clinical and laboratory findings of the disease were summarized and suggestions for future studies are provided. Copyright © 2016 Elsevier B.V. All rights reserved.

The Impact of Model and Rainfall Forcing Errors on Characterizing Soil Moisture Uncertainty in Land Surface Modeling

NASA Technical Reports Server (NTRS)

Maggioni, V.; Anagnostou, E. N.; Reichle, R. H.

2013-01-01

The contribution of rainfall forcing errors relative to model (structural and parameter) uncertainty in the prediction of soil moisture is investigated by integrating the NASA Catchment Land Surface Model (CLSM), forced with hydro-meteorological data, in the Oklahoma region. Rainfall-forcing uncertainty is introduced using a stochastic error model that generates ensemble rainfall fields from satellite rainfall products. The ensemble satellite rain fields are propagated through CLSM to produce soil moisture ensembles. Errors in CLSM are modeled with two different approaches: either by perturbing model parameters (representing model parameter uncertainty) or by adding randomly generated noise (representing model structure and parameter uncertainty) to the model prognostic variables. Our findings highlight that the method currently used in the NASA GEOS-5 Land Data Assimilation System to perturb CLSM variables poorly describes the uncertainty in the predicted soil moisture, even when combined with rainfall model perturbations. On the other hand, by adding model parameter perturbations to rainfall forcing perturbations, a better characterization of uncertainty in soil moisture simulations is observed. Specifically, an analysis of the rank histograms shows that the most consistent ensemble of soil moisture is obtained by combining rainfall and model parameter perturbations. When rainfall forcing and model prognostic perturbations are added, the rank histogram shows a U-shape at the domain average scale, which corresponds to a lack of variability in the forecast ensemble. The more accurate estimation of the soil moisture prediction uncertainty obtained by combining rainfall and parameter perturbations is encouraging for the application of this approach in ensemble data assimilation systems.

TOWARDS USING STABLE SPERMATOZOAL RNAS FOR PROGNOSTIC ASSESSMENT OF MALE FACTOR FERTILITY

EPA Science Inventory

Objective: To establish the stability of spermatozoal RNAs as a means to validate their use as a male fertility marker. Design: Semen samples were randomly selected for 1 of 3 cryopreservation treatments. Setting: An academic research environment. Patient(s): Men aged...

Biomarkers in Breast Cancer – An Update

PubMed Central

Schmidt, M.; Fasching, P. A.; Beckmann, M. W.; Kölbl, H.

2012-01-01

The therapy of choice for breast cancer patients requiring adjuvant chemo- or radiotherapy is increasingly guided by the principle of weighing the individual effectiveness of the therapy against the associated side effects. This has only been made possible by the discovery and validation of modern biomarkers. In the last decades and in the last few years some biomarkers have been integrated in clinical practice and a number have been included in modern study concepts. The importance of biomarkers lies not merely in their prognostic value indicating the future course of disease but also in their use to predict patient response to therapy. Due to the many subgroups, mathematical models and computer-assisted analysis are increasingly being used to assess the prognostic information obtained from established clinical and histopathological factors. In addition to describing some recent computer programmes this overview will focus on established molecular markers which have already been extensively validated in clinical practice and on new molecular markers identified by genome-wide studies. PMID:26640290

Tumor mutational load and immune parameters across metastatic Renal Cell Carcinoma (mRCC) risk groups

PubMed Central

de Velasco, Guillermo; Miao, Diana; Voss, Martin H.; Hakimi, A. Ari; Hsieh, James J.; Tannir, Nizar M.; Tamboli, Pheroze; Appleman, Leonard J.; Rathmell, W. Kimryn; Van Allen, Eliezer M.; Choueiri, Toni K.

2016-01-01

Patients with metastatic renal cell carcinoma (mRCC) have better overall survival when treated with nivolumab, a cancer immunotherapy that targets the immune checkpoint inhibitor programmed cell death 1 (PD-1), rather than everolimus (a chemical inhibitor of mTOR and immunosuppressant). Poor-risk mRCC patients treated with nivolumab seemed to experience the greatest overall survival benefit, compared to patients with favorable or intermediate-risk, in an analysis of the CheckMate-025 trial subgroup of the Memorial Sloan Kettering Cancer Center (MSKCC) prognostic risk groups. Here we explore whether tumor mutational load and RNA expression of specific immune parameters could be segregated by prognostic MSKCC risk strata and explain the survival seen in the poor-risk group. We queried whole exome transcriptome data in RCC patients (n = 54) included in The Cancer Genome Atlas that ultimately developed metastatic disease or were diagnosed with metastatic disease at presentation and did not receive immune checkpoint inhibitors. Nonsynonymous mutational load did not differ significantly by MSKCC risk group, nor was the expression of cytolytic genes –granzyme A and perforin – or selected immune checkpoint molecules different across MSKCC risk groups. In conclusion, this analysis found that mutational load and expression of markers of an active tumor microenvironment did not correlate with MSKCC risk prognostic classification in mRCC. PMID:27538576

Transcardiac increase in norepinephrine and prognosis in patients with chronic heart failure.

PubMed

Tsutamoto, Takayoshi; Nishiyama, Keizo; Sakai, Hiroshi; Tanaka, Toshinari; Fujii, Masanori; Yamamoto, Takashi; Yamaji, Masayuki; Horie, Minoru

2008-12-01

No previous study has compared the transcardiac gradient of norepinephrine (NE) and the prognosis of patients with chronic heart failure (CHF). To evaluate the prognostic role of the transcardiac gradient of NE in patients with CHF. We measured haemodynamic parameters and plasma levels of NE, brain natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) in the aortic root (AO) and coronary sinus (CS) in 356 consecutive patients with CHF. During a median follow-up of 3.5 years, 40 patients died. Transcardiac gradients of BNP (273+/-276 vs. 472+/-433 pg/mL, p<0.0001), NT-proBNP (417+/-700 vs. 928+/-1093 pg/mL, p<0.0001) and NE (114+/-160 vs. 473+/-992 pg/mL, p<0.0001) were significantly higher in non-survivors than survivors. After adjustment for clinical variables associated with CHF including haemodynamics and neurohumoral factors, the transcardiac gradient of NE (p<0.0001) and plasma log NT-proBNP (p<0.0001) were independent prognostic predictors. Among 67 patients in whom 123I-metaiodobenzylguanidine (MIBG) could be performed, transcardiac increase in NE was correlated with the washout rate (r=0.398, p=0.0009) and was a superior predictor of mortality than MIBG parameters on stepwise multivariable Cox proportional hazards regression analyses. The transcardiac increase in NE is an independent and useful prognostic predictor for evaluating the prognosis of CHF patients.

Current Pressure Transducer Application of Model-based Prognostics Using Steady State Conditions

NASA Technical Reports Server (NTRS)

Teubert, Christopher; Daigle, Matthew J.

2014-01-01

Prognostics is the process of predicting a system's future states, health degradation/wear, and remaining useful life (RUL). This information plays an important role in preventing failure, reducing downtime, scheduling maintenance, and improving system utility. Prognostics relies heavily on wear estimation. In some components, the sensors used to estimate wear may not be fast enough to capture brief transient states that are indicative of wear. For this reason it is beneficial to be capable of detecting and estimating the extent of component wear using steady-state measurements. This paper details a method for estimating component wear using steady-state measurements, describes how this is used to predict future states, and presents a case study of a current/pressure (I/P) Transducer. I/P Transducer nominal and off-nominal behaviors are characterized using a physics-based model, and validated against expected and observed component behavior. This model is used to map observed steady-state responses to corresponding fault parameter values in the form of a lookup table. This method was chosen because of its fast, efficient nature, and its ability to be applied to both linear and non-linear systems. Using measurements of the steady state output, and the lookup table, wear is estimated. A regression is used to estimate the wear propagation parameter and characterize the damage progression function, which are used to predict future states and the remaining useful life of the system.

Implementation of Remaining Useful Lifetime Transformer Models in the Fleet-Wide Prognostic and Health Management Suite

DOE Office of Scientific and Technical Information (OSTI.GOV)

Agarwal, Vivek; Lybeck, Nancy J.; Pham, Binh

Research and development efforts are required to address aging and reliability concerns of the existing fleet of nuclear power plants. As most plants continue to operate beyond the license life (i.e., towards 60 or 80 years), plant components are more likely to incur age-related degradation mechanisms. To assess and manage the health of aging plant assets across the nuclear industry, the Electric Power Research Institute has developed a web-based Fleet-Wide Prognostic and Health Management (FW-PHM) Suite for diagnosis and prognosis. FW-PHM is a set of web-based diagnostic and prognostic tools and databases, comprised of the Diagnostic Advisor, the Asset Faultmore » Signature Database, the Remaining Useful Life Advisor, and the Remaining Useful Life Database, that serves as an integrated health monitoring architecture. The main focus of this paper is the implementation of prognostic models for generator step-up transformers in the FW-PHM Suite. One prognostic model discussed is based on the functional relationship between degree of polymerization, (the most commonly used metrics to assess the health of the winding insulation in a transformer) and furfural concentration in the insulating oil. The other model is based on thermal-induced degradation of the transformer insulation. By utilizing transformer loading information, established thermal models are used to estimate the hot spot temperature inside the transformer winding. Both models are implemented in the Remaining Useful Life Database of the FW-PHM Suite. The Remaining Useful Life Advisor utilizes the implemented prognostic models to estimate the remaining useful life of the paper winding insulation in the transformer based on actual oil testing and operational data.« less

[Prognostic estimation in critical patients. Validation of a new and very simple system of prognostic estimation of survival in an intensive care unit].

PubMed

Abizanda, R; Padron, A; Vidal, B; Mas, S; Belenguer, A; Madero, J; Heras, A

2006-04-01

To make the validation of a new system of prognostic estimation of survival in critical patients (EPEC) seen in a multidisciplinar Intensive care unit (ICU). Prospective analysis of a patient cohort seen in the ICU of a multidisciplinar Intensive Medicine Service of a reference teaching hospital with 19 beds. Four hundred eighty four patients admitted consecutively over 6 months in 2003. Data collection of a basic minimum data set that includes patient identification data (gender, age), reason for admission and their origin, prognostic estimation of survival by EPEC, MPM II 0 and SAPS II (the latter two considered as gold standard). Mortality was evaluated on hospital discharge. EPEC validation was done with analysis of its discriminating capacity (ROC curve), calibration of its prognostic capacity (Hosmer Lemeshow C test), resolution of the 2 x 2 Contingency tables around different probability values (20, 50, 70 and mean value of prognostic estimation). The standardized mortality rate (SMR) for each one of the methods was calculated. Linear regression of the EPEC regarding the MPM II 0 and SAPS II was established and concordance analyses were done (Bland-Altman test) of the prediction of mortality by the three systems. In spite of an apparently good linear correlation, similar accuracy of prediction and discrimination capacity, EPEC is not well-calibrated (no likelihood of death greater than 50%) and the concordance analyses show that more than 10% of the pairs were outside the 95% confidence interval. In spite of its ease of application and calculation and of incorporating delay of admission in ICU as a variable, EPEC does not offer any predictive advantage on MPM II 0 or SAPS II, and its predictions adapt to reality worse.

Major prognostic role of Ki67 in localized adrenocortical carcinoma after complete resection.

PubMed

Beuschlein, Felix; Weigel, Jens; Saeger, Wolfgang; Kroiss, Matthias; Wild, Vanessa; Daffara, Fulvia; Libé, Rosella; Ardito, Arianna; Al Ghuzlan, Abir; Quinkler, Marcus; Oßwald, Andrea; Ronchi, Cristina L; de Krijger, Ronald; Feelders, Richard A; Waldmann, Jens; Willenberg, Holger S; Deutschbein, Timo; Stell, Anthony; Reincke, Martin; Papotti, Mauro; Baudin, Eric; Tissier, Frédérique; Haak, Harm R; Loli, Paola; Terzolo, Massimo; Allolio, Bruno; Müller, Hans-Helge; Fassnacht, Martin

2015-03-01

Recurrence of adrenocortical carcinoma (ACC) even after complete (R0) resection occurs frequently. The aim of this study was to identify markers with prognostic value for patients in this clinical setting. From the German ACC registry, 319 patients with the European Network for the Study of Adrenal Tumors stage I-III were identified. As an independent validation cohort, 250 patients from three European countries were included. Clinical, histological, and immunohistochemical markers were correlated with recurrence-free (RFS) and overall survival (OS). Although univariable analysis within the German cohort suggested several factors with potential prognostic power, upon multivariable adjustment only a few including age, tumor size, venous tumor thrombus (VTT), and the proliferation marker Ki67 retained significance. Among these, Ki67 provided the single best prognostic value for RFS (hazard ratio [HR] for recurrence, 1.042 per 1% increase; P < .0001) and OS (HR for death, 1.051; P < .0001) which was confirmed in the validation cohort. Accordingly, clinical outcome differed significantly between patients with Ki67 <10%, 10-19%, and ≥20% (for the German cohort: median RFS, 53.2 vs 31.6 vs 9.4 mo; median OS, 180.5 vs 113.5 vs 42.0 mo). Using the combined cohort prognostic scores including tumor size, VTT, and Ki67 were established. Although these scores discriminated slightly better between subgroups, there was no clinically meaningful advantage in comparison with Ki67 alone. This largest study on prognostic markers in localized ACC identified Ki67 as the single most important factor predicting recurrence in patients following R0 resection. Thus, evaluation of Ki67 indices should be introduced as standard grading in all pathology reports of patients with ACC.

Supraclavicular node disease is not an independent prognostic factor for survival of esophageal cancer patients treated with definitive chemoradiation.

PubMed

Jeene, Paul M; Versteijne, Eva; van Berge Henegouwen, Mark I; Bergmann, Jacques J G H M; Geijsen, Elisabeth D; van Laarhoven, Hanneke W M; Hulshof, Maarten C C M

2017-01-01

The prognostic value of supraclavicular lymph node (SCN) metastases in esophageal cancer is not well established. We analyzed the prognostic value of SCN disease in patients after definitive chemoradiation (dCRT) for esophageal cancer. We retrospectively analyzed 207 patients treated between 2003 and 2013 to identify the prognostic value of metastasis in the SCN on treatment failure and survival. All patients were treated with external beam radiotherapy (50.4 Gy in 28 fractions) combined with weekly concurrent paclitaxel 50 mg/m 2 and carboplatin AUC2. Median follow-up for patients alive was 43.3 months. The median overall survival (OS) for all patients was 17.5 months. OS at one, three and five years was 67%, 36% and 21%, respectively. For patients with metastasis in a SCN, OS was 23.6 months compared to 17.1 months for patients without metastasis in the SCN (p = .51). In multivariate analyses, higher cT status, cN status and adenocarcinoma were found to be prognostically unfavorable, but a positive SCN was not (p = .67). Median OS and median disease-free survival for tumors with SCN involvement and N0/1 disease was 49.0 months and 51.6 months, respectively, compared to 14.2 months and 8.2 months, respectively, in patients with N2/3 disease. In esophageal cancer treated with dCRT, the number of affected lymph nodes is an important independent prognostic factor, whereas involvement of a SCN is not. Supraclavicular lymph nodes should be considered as regional lymph nodes and treated with curative intent if the total number of involved lymph nodes is limited.

aPKCλ/ι is a beneficial prognostic marker for pancreatic neoplasms.

PubMed

Kato, Shingo; Akimoto, Kazunori; Nagashima, Yoji; Ishiguro, Hitoshi; Kubota, Kensuke; Kobayashi, Noritoshi; Hosono, Kunihiro; Watanabe, Seitaro; Sekino, Yusuke; Sato, Takamitsu; Sasaki, Kazunori; Nakaigawa, Noboru; Kubota, Yoshinobu; Inayama, Yoshiaki; Endo, Itaru; Ohno, Shigeo; Maeda, Shin; Nakajima, Atsushi

2013-01-01

Pancreatic cancer is a lethal disease. Overall survival is typically 6 months from diagnosis. Determination of prognostic factors in pancreatic cancer that would allow identification of patients who could potentially benefit from aggressive treatment is important. However, until date, there are no established reliable prognostic factors for pancreatic cancer patients. Herein, we propose a beneficial biomarker which is significantly correlated with the prognosis in pancreatic cancer patients. Atypical protein kinase C λ/ι (aPKCλ/ι) is overexpressed and has been implicated in the progression of several cancers. We tested the expression levels of aPKCλ/ι in two types of pancreatic neoplasm, pancreatic ductal adenocarcinoma (PDAC) and intraductal papillary mucinous neoplasms (IPMNs), by immunohistochemistry. Examination of the aPKCλ/ι expression levels in surgically resected specimens of PDCA (n = 115) demonstrated that the expression levels of aPKCλ/ιin PDAC had prognostic implications, independent of the Tumor-Node-Metastasis classification and World Health Organization tumor grade. In the case of IPMNs (n = 46) also, the expression levels of aPKCλ/ιin IPMN were found to be of prognostic importance, independent of the World Health Organization histological grade or morphological type. Interestingly, high expression levels of aPKCλ/ι were significantly correlated with a worse histological grade (p = 0.010) and advanced stage of the tumor (p = 0.0050) in IPMN patients. These findings suggest that high expression levels of aPKCλ/ι could be involved in the malignant transformation of IPMNs. Based on these observations, we propose the expression level of aPKCλ/ι as a prognostic marker common to different types of pancreatic neoplasms. Copyright © 2013 IAP and EPC. Published by Elsevier B.V. All rights reserved.

Correlation of HER-2 over-expression with clinico-pathological parameters in Tunisian breast carcinoma.

PubMed

Ayadi, Lobna; Khabir, Abdelmajid; Amouri, Habib; Karray, Sondes; Dammak, Abdallah; Guermazi, Mohamed; Boudawara, Tahya

2008-10-22

Breast carcinoma is a disease with a tremendous heterogeneity in its clinical behavior. Newer prognostic factors and predictors of response to therapy are needed. The aim of this study was to evaluate the expression of HER-2, estrogen receptor (ER) and progesterone receptors (PR) in breast carcinoma and to compare it with other prognostic parameters such as histological type and grade, tumor size, patients' age, and lymph node metastases. This is a retrospective study conducted in the department of pathology at Sfax University Hospital. Confirmed 155 Cases of breast carcinoma were reviewed in the period between January 2000 and December 2004. We used immunohistochemistry to evaluate the expression of HER-2, ER, and PR receptor and Chi-square and Fisher exact test to correlate immunohistochemical findings with prognostic parameters for breast carcinoma such as patients' age, tumor size, histological type, histological grade and lymph node status. The mean age of patients was 51.5 years, ranging from 22 to 89 years. 80 (51.6%) of the patients were below 50 years. The percentage of expression of HER-2, ER and PR was 26, 59.4, and 52.3%, respectively. HER-2 was over-expressed (3+) in 18.1% of the cases, was inversely related to ER expression (p = 0.00) and to PR expression (p = 0.048). This over-expression was also associated with a high tumor grade with marginal significance (p = 0.072). A negative correlation was noted between ER and PR expression and SBR grade (p = 0.000) and ER and age (p = 0.002). HER-2 over-expression was observed in 18.1% of Tunisian breast carcinoma affecting female patients. This group presents apparently an aggressive form of breast carcinoma with high histological grade and negative ER.

Dynamic 18F-FET PET in newly diagnosed astrocytic low-grade glioma identifies high-risk patients.

PubMed

Jansen, Nathalie L; Suchorska, Bogdana; Wenter, Vera; Eigenbrod, Sabina; Schmid-Tannwald, Christine; Zwergal, Andreas; Niyazi, Maximilian; Drexler, Mark; Bartenstein, Peter; Schnell, Oliver; Tonn, Jörg-Christian; Thon, Niklas; Kreth, Friedrich-Wilhelm; la Fougère, Christian

2014-02-01

Because the clinical course of low-grade gliomas in the individual adult patient varies considerably and is unpredictable, we investigated the prognostic value of dynamic (18)F-fluorethyltyrosine ((18)F-FET) PET in the early diagnosis of astrocytic low-grade glioma (World Health Organization grade II). Fifty-nine patients with newly diagnosed low-grade glioma and dynamic (18)F-FET PET before histopathologic assessment were retrospectively investigated. (18)F-FET PET analysis comprised a qualitative visual classification of lesions; assessment of the semiquantitative parameters maximal, mean, and total standardized uptake value as ratio to background and biologic tumor volume; and dynamic analysis of intratumoral (18)F-FET uptake over time (increasing vs. decreasing time-activity curves). The correlation between PET parameters and progression-free survival, overall survival, and time to malignant transformation was investigated. (18)F-FET uptake greater than the background level was found in 34 of 59 tumors. Dynamic (18)F-FET uptake analysis was available for 30 of these 34 patients. Increasing and decreasing time-activity curves were found in 18 and 12 patients, respectively. Neither the qualitative factor presence or absence of (18)F-FET uptake nor any of the semiquantitative uptake parameters significantly influenced clinical outcome. In contrast, decreasing time-activity curves in the kinetic analysis were highly prognostic for shorter progression-free survival and time to malignant transformation (P < 0.001). Absence of (18)F-FET uptake in newly diagnosed astrocytic low-grade glioma does not generally indicate an indolent disease course. Among the (18)F-FET-positive gliomas, decreasing time-activity curves in dynamic (18)F-FET PET constitute an unfavorable prognostic factor in astrocytic low-grade glioma and, by identifying high-risk patients, may ease treatment decisions.

Prognostic value of the new Grade Groups in Prostate Cancer: a multi-institutional European validation study.

PubMed

Mathieu, R; Moschini, M; Beyer, B; Gust, K M; Seisen, T; Briganti, A; Karakiewicz, P; Seitz, C; Salomon, L; de la Taille, A; Rouprêt, M; Graefen, M; Shariat, S F

2017-06-01

We aimed to assess the prognostic relevance of the new Grade Groups in Prostate Cancer (PCa) within a large cohort of European men treated with radical prostatectomy (RP). Data from 27 122 patients treated with RP at seven European centers were analyzed. We investigated the prognostic performance of the new Grade Groups (based on Gleason score 3+3, 3+4, 4+3, 8 and 9-10) on biopsy and RP specimen, adjusted for established clinical and pathological characteristics. Multivariable Cox proportional hazards regression models assessed the association of new Grade Groups with biochemical recurrence (BCR). Prognostic accuracies of the models were assessed using Harrell's C-index. Median follow-up was 29 months (interquartile range, 13-54). The 4-year estimated BCR-free survival (bRFS) for biopsy Grade Groups 1-5 were 91.3, 81.6, 69.8, 60.3 and 44.4%, respectively. The 4-year estimated bRFS for RP Grade Groups 1-5 were 96.1%, 86.7%, 67.0%, 63.1% and 41.0%, respectively. Compared with Grade Group 1, all other Grade Groups based both on biopsy and RP specimen were independently associated with a lower bRFS (all P<0.01). Adjusted pairwise comparisons revealed statistically differences between all Grade Groups, except for group 3 and 4 on RP specimen (P=0.10). The discriminations of the multivariable base prognostic models based on the current three-tier and the new five-tier systems were not clinically different (0.3 and 0.9% increase in discrimination for clinical and pathological model). We validated the independent prognostic value of the new Grade Groups on biopsy and RP specimen from European PCa men. However, it does not improve the accuracies of prognostic models by a clinically significant margin. Nevertheless, this new classification may help physicians and patients estimate disease aggressiveness with a user-friendly, clinically relevant and reproducible method.

Prognostic value of interleukin-6 and interleukin-6 receptor in organ-confined clear-cell renal cell carcinoma: a 5-year conditional cancer-specific survival analysis.

PubMed

Fu, Qiang; Chang, Yuan; An, Huimin; Fu, Hangcheng; Zhu, Yu; Xu, Le; Zhang, Weijuan; Xu, Jiejie

2015-12-01

Interleukin-6 (IL-6) is the major cytokine that induces transcriptional acute and chronic inflammation responses, and was recently incorporated as a recurrence prognostication signature for localised clear-cell renal cell carcinoma (ccRCC). As the prognostic efficacy of initial risk factors may ebb during long-term practice, we aim to report conditional cancer-specific survival (CCSS) of RCC patients and evaluate the impact of IL-6 as well as its receptor (IL-6R) to offer more relevant prognostic information accounting for elapsing time. We enrolled 180 histologically proven localised ccRCC patients who underwent nephrectomy between 2001 and 2004 with available pathologic information. Five-year CCSS was determined and stratified by future prognostic factors. Constant Cox regression analysis and Harrell's concordance index were used to indicate the predictive accuracy of established models. The 5-year CCSS of organ-confined ccRCC patients with both IL-6- and IL-6R-positive expression was 52% at year 2 after surgery, which was close to locally advanced patients (48%, P=0.564) and was significantly poorer than organ-confined patients with IL-6- or IL-6R-negative expression (89%, P<0.001). Multivariate analyses proved IL-6 and IL-6R as independent predictors after adjusting for demographic factors. Concordance index of pT-IL-6-IL-6R risk stratification was markedly higher compared with the stage, size, grade and necrosis prognostic model (0.724 vs 0.669, P=0.002) or UCLA Integrated Staging System (0.724 vs 0.642, P=0.007) in organ-confined ccRCC population during the first 5 years. Combined IL-6 and IL-6R coexpression emerges as an independent early-stage immunologic prognostic factor for organ-confined ccRCC patients.

An inflammation-based prognostic score (mGPS) predicts cancer survival independent of tumour site: a Glasgow Inflammation Outcome Study.

PubMed

Proctor, M J; Morrison, D S; Talwar, D; Balmer, S M; O'Reilly, D S J; Foulis, A K; Horgan, P G; McMillan, D C

2011-02-15

A selective combination of C-reactive protein and albumin (termed the modified Glasgow Prognostic Score, mGPS) has been shown to have prognostic value, independent of tumour stage, in lung, gastrointestinal and renal cancers. It is also of interest that liver function tests such as bilirubin, alkaline phosphatase and γ-glutamyl transferase, as well as serum calcium, have also been reported to predict cancer survival. The aim of the present study was to examine the relationship between an inflammation-based prognostic score (mGPS), biochemical parameters, tumour site and survival in a large cohort of patients with cancer. Patients (n=21,669) who had an incidental blood sample taken between 2000 and 2006 for C-reactive protein, albumin and calcium (and liver function tests where available) and a diagnosis of cancer were identified. Of this group 9608 patients who had an ongoing malignant process were studied (sampled within 2 years before diagnosis). Also a subgroup of 5397 sampled at the time of diagnosis (sampled within 2 months prior to diagnosis) were examined. Cancers were grouped by tumour site in accordance with International Classification of Diseases 10 (ICD 10). On follow up, there were 6005 (63%) deaths of which 5122 (53%) were cancer deaths. The median time from blood sampling to diagnosis was 1.4 months. Increasing age, male gender and increasing deprivation was associated with a reduced 5-year overall and cancer-specific survival (all P<0.001). An elevated mGPS, adjusted calcium, bilirubin, alkaline phosphatase, aspartate transaminase, alanine transaminase and γ-glutamyl transferase were associated with a reduced 5-year overall and cancer-specific survival (independent of age, sex and deprivation in all patients sampled), as well as within the time of diagnosis subgroup (all P<0.001). An increasing mGPS was predictive of a reduced cancer-specific survival in all cancers (all P<0.001). The results of the present study indicate that the mGPS is a powerful prognostic factor when compared with other biochemical parameters and independent of tumour site in patients with cancer.

The prognostic role of exercise echocardiography in heart failure.

PubMed

Rubiś, Paweł; Drabik, Leszek; Kopeć, Grzegorz; Olszowska, Maria; Płazak, Wojciech; Podolec, Piotr

2011-01-01

Gradual impairment of exercise tolerance is the commonest sign of heart failure (HF). Little is known as to which cardiac contributors of poor exercise capacity carry an independent prognostic information in HF. We investigated the prognostic role of exercise echocardiography (ex-echo) in HF patients. We studied 85 consecutive, symptomatic HF patients (66 males, mean age 62.5 ± 11.8 [range 21-83] years, mean left ventricular ejection fraction [LVEF] 27.2 ± 9.5%). The end-point was all-cause mortality. During the follow-up period (mean 43 ± 21 months) 21 patients died. Resting echocardiography and ex-echo, with the simultaneous measurement of peak oxygen uptake (VO(2peak)), was performed in each patient using a semi-supine ergometer (20 W, 2-min increments). Apart from conventional assessment of systolic and diastolic function (EF, E/A, DT, IVRT) or right ventricular systolic pressure (RVSP), tissue Doppler imaging was used for the assessment of LV and RV peak velocity (IVV) as well as acceleration during isovolumic contraction (IVA), peak velocity during ejection phase (S'), peak early diastolic velocity (E'), peak late diastolic velocity (A'), and ratio of early diastolic mitral/tricuspid velocity to peak early diastolic velocity (E/E'). Patients who died were significantly older, had lower exercise capacity, more advanced HF, greater impairment of baseline systolic function, higher baseline pulmonary artery systolic pressure, and most importantly a lack of improvement in EF, diastolic function, and further increase of RVSP during exercise. Out of all echocardiographic parameters, only peak stress EF (x(2) 6.1; p = 0.01), baseline and peak exercise RVSP (x(2) 12.5 and c(2) 18.7; p 〈 0.001; respectively), and mitral E/E' ratio (x(2) 8.9; p 〈 0.01) were univariate predictors of prognosis and remained independently prognostic when adjusted for age and sex but were eliminated from the model by NT-proBNP. During exercise, more severe systolic and diastolic dysfunction with the elevation of pulmonary arterial pressure is more prevalent in HF patients who have a poorer outcome. The estimation of common parameters such as EF, RVSP and E/E' using ex-echo, provides prognostic information in HF.

Visual and semiquantitative 11C-methionine PET: an independent prognostic factor for survival of newly diagnosed and treatment-naïve gliomas.

PubMed

Poetsch, Nina; Woehrer, Adelheid; Gesperger, Johanna; Furtner, Julia; Haug, Alexander R; Wilhelm, Dorothee; Widhalm, Georg; Karanikas, Georgios; Weber, Michael; Rausch, Ivo; Mitterhauser, Markus; Wadsak, Wolfgang; Hacker, Marcus; Preusser, Matthias; Traub-Weidinger, Tatjana

2018-02-19

Few data exist regarding the prognostic value of L-[S-methyl-11C]methionine (MET) PET for treatment-naïve gliomas. A total of 160 glioma patients (89 men, 71 women; mean age: 45, range 18-84 y) underwent a MET PET prior to any therapy. The PET scans were evaluated visually and semiquantitatively by tumor-to-background (T/N) ratio thresholds chosen by analysis of receiver operating characteristics. Additionally, isocitrate dehydrogenase 1-R132H (IDH1-R132H) immunohistochemistry was performed. Survival analysis was done using Kaplan-Meier estimates and the Cox proportional hazards model. Significantly shorter mean survival times (7.2 vs 8.6 y; P = 0.024) were seen in patients with amino acid avid gliomas (n = 137) compared with visually negative tumors (n = 33) in MET PET. T/N ratio thresholds of 2.1 and 3.5 were significantly associated with survival (10.3 vs 7 vs 4.3 y; P < 0.001). Mean survival differed significantly using the median T/N ratio of 2.4 as cutoff, independent of histopathology (P < 0.01; mean survival: 10.2 ± 0.8 y vs 5.5 ± 0.6 y). In the subgroup of 142 glioma patients characterized by IDH1-R132H status, METT/N ratio demonstrated a significant prognostic impact in IDH1-R132H wildtype astrocytomas and glioblastoma (P = 0.001). Additionally, multivariate testing revealed semiquantitative MET PET as an independent prognostic parameter for treatment-naïve glioma patients without (P = 0.031) and with IDH1-R132H characterization of gliomas (P = 0.024; odds ratio 1.57). This retrospective analysis demonstrates the value of MET PET as a prognostic parameter on survival in treatment-naïve glioma patients. © The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Predictive value of seven preoperative prognostic scoring systems for spinal metastases

PubMed Central

Leithner, Andreas; Radl, Roman; Gruber, Gerald; Hochegger, Markus; Leithner, Katharina; Welkerling, Heike; Rehak, Peter

2008-01-01

Predicting prognosis is the key factor in selecting the proper treatment modality for patients with spinal metastases. Therefore, various assessment systems have been designed in order to provide a basis for deciding the course of treatment. Such systems have been proposed by Tokuhashi, Sioutos, Tomita, Van der Linden, and Bauer. The scores differ greatly in the kind of parameters assessed. The aim of this study was to evaluate the prognostic value of each score. Eight parameters were assessed for 69 patients (37 male, 32 female): location, general condition, number of extraspinal bone metastases, number of spinal metastases, visceral metastases, primary tumour, severity of spinal cord palsy, and pathological fracture. Scores according to Tokuhashi (original and revised), Sioutos, Tomita, Van der Linden, and Bauer were assessed as well as a modified Bauer score without scoring for pathologic fracture. Nineteen patients were still alive as of September 2006 with a minimum follow-up of 12 months. All other patients died after a mean period of 17 months after operation. The mean overall survival period was only 3 months for lung cancer, followed by prostate (7 months), kidney (23 months), breast (35 months), and multiple myeloma (51 months). At univariate survival analysis, primary tumour and visceral metastases were significant parameters, while Karnofsky score was only significant in the group including myeloma patients. In multivariate analysis of all seven parameters assessed, primary tumour and visceral metastases were the only significant parameters. Of all seven scoring systems, the original Bauer score and a Bauer score without scoring for pathologic fracture had the best association with survival (P < 0.001). The data of the present study emphasize that the original Bauer score and a modified Bauer score without scoring for pathologic fracture seem to be practicable and highly predictive preoperative scoring systems for patients with spinal metastases. However, decision for or against surgery should never be based alone on a prognostic score but should take symptoms like pain or neurological compromise into account. PMID:18787846

Cryptochrome-1 expression: a new prognostic marker in B-cell chronic lymphocytic leukemia.

PubMed

Lewintre, Eloisa Jantus; Martín, Cristina Reinoso; Ballesteros, Carlos García; Montaner, David; Rivera, Rosa Farrás; Mayans, José Ramón; García-Conde, Javier

2009-02-01

Chronic lymphocytic leukemia is an adult-onset leukemia with a heterogeneous clinical behavior. When chronic lymphocytic leukemia cases were divided on the basis of IgV(H) mutational status, widely differing clinical courses were revealed. Since IgV(H) sequencing is difficult to perform in a routine diagnostic laboratory, finding a surrogate for IgV(H) mutational status seems an important priority. In the present study, we proposed the use of Cryptochrome-1 as a new prognostic marker in early-stage chronic lymphocytic leukemia. Seventy patients (Binet stage A, without treatment) were included in the study. We correlated Cryptochrome-1 mRNA with well established prognostic markers such as IgV(H) mutations, ZAP70, LPL or CD38 expression and chromosomal abnormalities. High Cryptochrome-1 expression correlated with IgV(H) unmutated samples. In addition, Cryptochrome-1 was a valuable predictor of disease progression in early-stage chronic lymphocytic leukemia, therefore it can be introduced in clinical practice with the advantage of a simplified method of quantification.

Usefulness and prognostic value of biomarkers in patients with community-acquired pneumonia in the emergency department.

PubMed

Julián-Jiménez, Agustín; González Del Castillo, Juan; Candel, Francisco Javier

2017-06-07

Between all patients treated in the Emergency Department (ED), 1.35% are diagnosed with community-acquired pneumonia (CAP). CAP is the main cause of death due to infectious disease (10-14%) and the most frequent reason of sepsis-septic shock in the ED. In the last decade, the search for objective tools to help establishing an early diagnosis, bacterial aetiology, severity, suspicion of bacteremia and the prognosis of mortality has increased. Biomarkers have shown their usefulness in this matter. Procalcitonin (obtains the highest accuracy for CAP diagnosis, bacterial aetiology and the presence of bacteremia), lactate (biomarker of hypoxia and tissue hypoperfusion) and proadrenomedullin (which has the greatest accuracy to predict mortality which in combination with the prognostic severity scales obtains even better results). The aim of this review is to highlight recently published scientific evidence and to compare the utility and prognostic accuracy of the biomarkers in CAP patients treated in the ED. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Clinical impact of 18 F-FDG positron emission tomography/CT on adenoid cystic carcinoma of the head and neck.

PubMed

Jung, Ji-Hoon; Lee, Sang-Woo; Son, Seung Hyun; Kim, Choon-Young; Lee, Chang-Hee; Jeong, Ju Hye; Jeong, Shin Young; Ahn, Byeong-Cheol; Lee, Jaetae

2017-03-01

The purpose of this retrospective study was to assess the diagnostic value of 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT and the prognostic value of metabolic PET parameters in patients with adenoid cystic carcinoma of the head and neck (ACCHN). Forty patients with newly diagnosed ACCHN were enrolled in this study. We investigated the diagnostic value of 18 F-FDG PET/CT for detecting and staging compared to conventional CT. Kaplan-Meier survival analysis for progression-free survival (PFS) was performed with clinicopathological factors and metabolic PET parameters. The 18 F-FDG PET/CT showed comparable sensitivity (92.3%) to conventional CT for lesion detection, and changed staging and management plan in 6 patients (15.0%). Lower PFS rates were associated with advanced T classification, advanced TNM classification, high maximum standardized uptake value (SUVmax; >5.1), and high total lesion glycolysis (>40.1) of the primary tumor. The 18 F-FDG PET/CT can provide additional information for initial staging, and metabolic PET parameters may serve as prognostic factors of ACCHN. © 2016 Wiley Periodicals, Inc. Head Neck 39: 447-455, 2017. © 2016 Wiley Periodicals, Inc.

A prognostic classifier for patients with colorectal cancer liver metastasis, based on AURKA, PTGS2 and MMP9.

PubMed

Goos, Jeroen A C M; Coupé, Veerle M H; van de Wiel, Mark A; Diosdado, Begoña; Delis-Van Diemen, Pien M; Hiemstra, Annemieke C; de Cuba, Erienne M V; Beliën, Jeroen A M; Menke-van der Houven van Oordt, C Willemien; Geldof, Albert A; Meijer, Gerrit A; Hoekstra, Otto S; Fijneman, Remond J A

2016-01-12

Prognosis of patients with colorectal cancer liver metastasis (CRCLM) is estimated based on clinicopathological models. Stratifying patients based on tumor biology may have additional value. Tissue micro-arrays (TMAs), containing resected CRCLM and corresponding primary tumors from a multi-institutional cohort of 507 patients, were immunohistochemically stained for 18 candidate biomarkers. Cross-validated hazard rate ratios (HRRs) for overall survival (OS) and the proportion of HRRs with opposite effect (P(HRR < 1) or P(HRR > 1)) were calculated. A classifier was constructed by classification and regression tree (CART) analysis and its prognostic value determined by permutation analysis. Correlations between protein expression in primary tumor-CRCLM pairs were calculated. Based on their putative prognostic value, EGFR (P(HRR < 1) = .02), AURKA (P(HRR < 1) = .02), VEGFA (P(HRR < 1) = .02), PTGS2 (P(HRR < 1) = .01), SLC2A1 (P(HRR > 1) < 01), HIF1α (P(HRR > 1) = .06), KCNQ1 (P(HRR > 1) = .09), CEA (P (HRR > 1) = .05) and MMP9 (P(HRR < 1) = .07) were included in the CART analysis (n = 201). The resulting classifier was based on AURKA, PTGS2 and MMP9 expression and was associated with OS (HRR 2.79, p < .001), also after multivariate analysis (HRR 3.57, p < .001). The prognostic value of the biomarker-based classifier was superior to the clinicopathological model (p = .001). Prognostic value was highest for colon cancer patients (HRR 5.71, p < .001) and patients not treated with systemic therapy (HRR 3.48, p < .01). Classification based on protein expression in primary tumors could be based on AURKA expression only (HRR 2.59, p = .04). A classifier was generated for patients with CRCLM with improved prognostic value compared to the standard clinicopathological prognostic parameters, which may aid selection of patients who may benefit from adjuvant systemic therapy.

Imaging Intratumor Heterogeneity: Role in Therapy Response, Resistance, and Clinical Outcome

PubMed Central

O’Connor, James P.B.; Rose, Chris J.; Waterton, John C.; Carano, Richard A.D.; Parker, Geoff J.M.; Jackson, Alan

2014-01-01

Tumors exhibit genomic and phenotypic heterogeneity which has prognostic significance and may influence response to therapy. Imaging can quantify the spatial variation in architecture and function of individual tumors through quantifying basic biophysical parameters such as density or MRI signal relaxation rate; through measurements of blood flow, hypoxia, metabolism, cell death and other phenotypic features; and through mapping the spatial distribution of biochemical pathways and cell signaling networks. These methods can establish whether one tumor is more or less heterogeneous than another and can identify sub-regions with differing biology. In this article we review the image analysis methods currently used to quantify spatial heterogeneity within tumors. We discuss how analysis of intratumor heterogeneity can provide benefit over more simple biomarkers such as tumor size and average function. We consider how imaging methods can be integrated with genomic and pathology data, rather than be developed in isolation. Finally, we identify the challenges that must be overcome before measurements of intratumoral heterogeneity can be used routinely to guide patient care. PMID:25421725

Cutaneous Lymphoma International Consortium Study of Outcome in Advanced Stages of Mycosis Fungoides and Sézary Syndrome: Effect of Specific Prognostic Markers on Survival and Development of a Prognostic Model

PubMed Central

Scarisbrick, Julia J.; Prince, H. Miles; Vermeer, Maarten H.; Quaglino, Pietro; Horwitz, Steven; Porcu, Pierluigi; Stadler, Rudolf; Wood, Gary S.; Beylot-Barry, Marie; Pham-Ledard, Anne; Foss, Francine; Girardi, Michael; Bagot, Martine; Michel, Laurence; Battistella, Maxime; Guitart, Joan; Kuzel, Timothy M.; Martinez-Escala, Maria Estela; Estrach, Teresa; Papadavid, Evangelia; Antoniou, Christina; Rigopoulos, Dimitis; Nikolaou, Vassilki; Sugaya, Makoto; Miyagaki, Tomomitsu; Gniadecki, Robert; Sanches, José Antonio; Cury-Martins, Jade; Miyashiro, Denis; Servitje, Octavio; Muniesa, Cristina; Berti, Emilio; Onida, Francesco; Corti, Laura; Hodak, Emilia; Amitay-Laish, Iris; Ortiz-Romero, Pablo L.; Rodríguez-Peralto, Jose L.; Knobler, Robert; Porkert, Stefanie; Bauer, Wolfgang; Pimpinelli, Nicola; Grandi, Vieri; Cowan, Richard; Rook, Alain; Kim, Ellen; Pileri, Alessandro; Patrizi, Annalisa; Pujol, Ramon M.; Wong, Henry; Tyler, Kelly; Stranzenbach, Rene; Querfeld, Christiane; Fava, Paolo; Maule, Milena; Willemze, Rein; Evison, Felicity; Morris, Stephen; Twigger, Robert; Talpur, Rakhshandra; Kim, Jinah; Ognibene, Grant; Li, Shufeng; Tavallaee, Mahkam; Hoppe, Richard T.; Duvic, Madeleine; Whittaker, Sean J.; Kim, Youn H.

2015-01-01

Purpose Advanced-stage mycosis fungoides (MF; stage IIB to IV) and Sézary syndrome (SS) are aggressive lymphomas with a median survival of 1 to 5 years. Clinical management is stage based; however, there is wide range of outcome within stages. Published prognostic studies in MF/SS have been single-center trials. Because of the rarity of MF/SS, only a large collaboration would power a study to identify independent prognostic markers. Patients and Methods Literature review identified the following 10 candidate markers: stage, age, sex, cutaneous histologic features of folliculotropism, CD30 positivity, proliferation index, large-cell transformation, WBC/lymphocyte count, serum lactate dehydrogenase, and identical T-cell clone in blood and skin. Data were collected at specialist centers on patients diagnosed with advanced-stage MF/SS from 2007. Each parameter recorded at diagnosis was tested against overall survival (OS). Results Staging data on 1,275 patients with advanced MF/SS from 29 international sites were included for survival analysis. The median OS was 63 months, with 2- and 5-year survival rates of 77% and 52%, respectively. The median OS for patients with stage IIB disease was 68 months, but patients diagnosed with stage III disease had slightly improved survival compared with patients with stage IIB, although patients diagnosed with stage IV disease had significantly worse survival (48 months for stage IVA and 33 months for stage IVB). Of the 10 variables tested, four (stage IV, age > 60 years, large-cell transformation, and increased lactate dehydrogenase) were independent prognostic markers for a worse survival. Combining these four factors in a prognostic index model identified the following three risk groups across stages with significantly different 5-year survival rates: low risk (68%), intermediate risk (44%), and high risk (28%). Conclusion To our knowledge, this study includes the largest cohort of patients with advanced-stage MF/SS and identifies markers with independent prognostic value, which, used together in a prognostic index, may be useful to stratify advanced-stage patients. PMID:26438120

Cutaneous Lymphoma International Consortium Study of Outcome in Advanced Stages of Mycosis Fungoides and Sézary Syndrome: Effect of Specific Prognostic Markers on Survival and Development of a Prognostic Model.

PubMed

Scarisbrick, Julia J; Prince, H Miles; Vermeer, Maarten H; Quaglino, Pietro; Horwitz, Steven; Porcu, Pierluigi; Stadler, Rudolf; Wood, Gary S; Beylot-Barry, Marie; Pham-Ledard, Anne; Foss, Francine; Girardi, Michael; Bagot, Martine; Michel, Laurence; Battistella, Maxime; Guitart, Joan; Kuzel, Timothy M; Martinez-Escala, Maria Estela; Estrach, Teresa; Papadavid, Evangelia; Antoniou, Christina; Rigopoulos, Dimitis; Nikolaou, Vassilki; Sugaya, Makoto; Miyagaki, Tomomitsu; Gniadecki, Robert; Sanches, José Antonio; Cury-Martins, Jade; Miyashiro, Denis; Servitje, Octavio; Muniesa, Cristina; Berti, Emilio; Onida, Francesco; Corti, Laura; Hodak, Emilia; Amitay-Laish, Iris; Ortiz-Romero, Pablo L; Rodríguez-Peralto, Jose L; Knobler, Robert; Porkert, Stefanie; Bauer, Wolfgang; Pimpinelli, Nicola; Grandi, Vieri; Cowan, Richard; Rook, Alain; Kim, Ellen; Pileri, Alessandro; Patrizi, Annalisa; Pujol, Ramon M; Wong, Henry; Tyler, Kelly; Stranzenbach, Rene; Querfeld, Christiane; Fava, Paolo; Maule, Milena; Willemze, Rein; Evison, Felicity; Morris, Stephen; Twigger, Robert; Talpur, Rakhshandra; Kim, Jinah; Ognibene, Grant; Li, Shufeng; Tavallaee, Mahkam; Hoppe, Richard T; Duvic, Madeleine; Whittaker, Sean J; Kim, Youn H

2015-11-10

Advanced-stage mycosis fungoides (MF; stage IIB to IV) and Sézary syndrome (SS) are aggressive lymphomas with a median survival of 1 to 5 years. Clinical management is stage based; however, there is wide range of outcome within stages. Published prognostic studies in MF/SS have been single-center trials. Because of the rarity of MF/SS, only a large collaboration would power a study to identify independent prognostic markers. Literature review identified the following 10 candidate markers: stage, age, sex, cutaneous histologic features of folliculotropism, CD30 positivity, proliferation index, large-cell transformation, WBC/lymphocyte count, serum lactate dehydrogenase, and identical T-cell clone in blood and skin. Data were collected at specialist centers on patients diagnosed with advanced-stage MF/SS from 2007. Each parameter recorded at diagnosis was tested against overall survival (OS). Staging data on 1,275 patients with advanced MF/SS from 29 international sites were included for survival analysis. The median OS was 63 months, with 2- and 5-year survival rates of 77% and 52%, respectively. The median OS for patients with stage IIB disease was 68 months, but patients diagnosed with stage III disease had slightly improved survival compared with patients with stage IIB, although patients diagnosed with stage IV disease had significantly worse survival (48 months for stage IVA and 33 months for stage IVB). Of the 10 variables tested, four (stage IV, age > 60 years, large-cell transformation, and increased lactate dehydrogenase) were independent prognostic markers for a worse survival. Combining these four factors in a prognostic index model identified the following three risk groups across stages with significantly different 5-year survival rates: low risk (68%), intermediate risk (44%), and high risk (28%). To our knowledge, this study includes the largest cohort of patients with advanced-stage MF/SS and identifies markers with independent prognostic value, which, used together in a prognostic index, may be useful to stratify advanced-stage patients. © 2015 by American Society of Clinical Oncology.

Effect of nutritional status on mortality in patients undergoing coronary artery bypass grafting.

PubMed

Keskin, Muhammed; İpek, Göktük; Aldağ, Mustafa; Altay, Servet; Hayıroğlu, Mert İlker; Börklü, Edibe Betül; İnan, Duygu; Kozan, Ömer

2018-04-01

The prognostic effects of poor nutritional status and cardiac cachexia on coronary artery disease (CAD) are not clearly understood. A well-accepted nutritional status parameter, the prognostic nutritional index (PNI), which was first demonstrated to be valuable in patients with cancer and those undergoing gastrointestinal surgery, was introduced to patients requiring coronary artery bypass grafting (CABG). The aim of the present study was to evaluate the prognostic value of PNI in patients with CAD undergoing CABG. We evaluated the in-hospital and long-term (3-y) prognostic effect of PNI on 644 patients with CAD undergoing CABG. Baseline characteristics and outcomes were compared among the patients by PNI and categorized accordingly: Q1, Q2, Q3, and Q4. Patients with lower PNI had significantly higher in-hospital and long-term mortality. Patients with lower PNI levels (Q1) had higher in-hospital mortality and had 12 times higher mortality rates than those with higher PNI levels (Q4). The higher PNI group had the lower rates and was used as the reference. Long-term mortality was higher in patients with lower PNI (Q1)-4.9 times higher than in the higher PNI group (Q4). In-hospital and long-term mortality rates were similar in the non-lower PNI groups (Q2-4). The present study demonstrated that PNI, calculated based on serum albumin level and lymphocyte count, is an independent prognostic factor for mortality in patients undergoing CABG. Copyright © 2017 Elsevier Inc. All rights reserved.

Nailfold capillaroscopy for day-to-day clinical use: construction of a simple scoring modality as a clinical prognostic index for digital trophic lesions.

PubMed

Smith, Vanessa; De Keyser, Filip; Pizzorni, Carmen; Van Praet, Jens T; Decuman, Saskia; Sulli, Alberto; Deschepper, Ellen; Cutolo, Maurizio

2011-01-01

Construction of a simple nailfold videocapillaroscopic (NVC) scoring modality as a prognostic index for digital trophic lesions for day-to-day clinical use. An association with a single simple (semi)-quantitatively scored NVC parameter, mean score of capillary loss, was explored in 71 consecutive patients with systemic sclerosis (SSc), and reliable reduction in the number of investigated fields (F32-F16-F8-F4). The cut-off value of the prognostic index (mean score of capillary loss calculated over a reduced number of fields) for present/future digital trophic lesions was selected by receiver operating curve (ROC) analysis. Reduction in the number of fields for mean score of capillary loss was reliable from F32 to F8 (intraclass correlation coefficient of F16/F32: 0.97; F8/F32: 0.90). Based on ROC analysis, a prognostic index (mean score of capillary loss as calculated over F8) with a cut-off value of 1.67 is proposed. This value has a sensitivity of 72.22/70.00, specificity of 70.59/69.77, positive likelihood ratio of 2.46/2.32 and a negative likelihood ratio of 0.39/0.43 for present/future digital trophic lesions. A simple prognostic index for digital trophic lesions for daily use in SSc clinics is proposed, limited to the mean score of capillary loss as calculated over eight fields (8 fingers, 1 field per finger).

Telomere length is an independent prognostic marker in MDS but not in de novo AML.

PubMed

Williams, Jenna; Heppel, Nicole H; Britt-Compton, Bethan; Grimstead, Julia W; Jones, Rhiannon E; Tauro, Sudhir; Bowen, David T; Knapper, Steven; Groves, Michael; Hills, Robert K; Pepper, Chris; Baird, Duncan M; Fegan, Chris

2017-07-01

Telomere dysfunction is implicated in the generation of large-scale genomic rearrangements that drive progression to malignancy. In this study we used high-resolution single telomere length analysis (STELA) to examine the potential role of telomere dysfunction in 80 myelodysplastic syndrome (MDS) and 95 de novo acute myeloid leukaemia (AML) patients. Despite the MDS cohort being older, they had significantly longer telomeres than the AML cohort (P < 0·0001) where telomere length was also significantly shorter in younger AML patients (age <60 years) (P = 0·02) and in FLT3 internal tandem duplication-mutated AML patients (P = 0·03). Using a previously determined telomere length threshold for telomere dysfunction (3·81 kb) did not provide prognostic resolution in AML [Hazard ratio (HR) = 0·68, P = 0·2]. In contrast, the same length threshold was highly prognostic for overall survival in the MDS cohort (HR = 5·0, P < 0·0001). Furthermore, this telomere length threshold was an independent parameter in multivariate analysis when adjusted for age, gender, cytogenetic risk group, number of cytopenias and International Prognostic Scoring System (IPSS) score (HR = 2·27, P < 0·0001). Therefore, telomere length should be assessed in a larger prospective study to confirm its prognostic role in MDS with a view to integrating this variable into a revised IPSS. © 2017 John Wiley & Sons Ltd.

Prognostic significance of ZNF217 expression in gastric carcinoma.

PubMed

Shida, Atsuo; Fujioka, Shuichi; Kurihara, Hideaki; Ishibashi, Yoshio; Mitsumori, Norio; Omura, Nobuo; Yanaga, Katsuhiko

2014-09-01

The zinc finger protein ZNF217 is a candidate oncogene in breast cancer and ovarian clear cell cancer. The purpose of the present study was to clarify the significance of this protein's expression in gastric carcinoma and to evaluate the outcome of these patients. Using paraffin-embedded specimens from 84 patients with gastric cancer, ZNF217 protein was detected using an anti-ZNF217 goat polyclonal antibody. We evaluated the ZNF217 protein expression in relation to patient outcome and clinicopathological parameters. The ZNF217 protein was expressed in 34 (40.5%) tumor sections. Patients with ZNF217-negative tumors had better relapse-free survival (RFS) and overall survival (OS) than those with ZNF217-positive tumors by the log-rank test. Notably, multivariate analysis indicated that ZNF217 was an independent prognostic factor for RFS. ZNF217 expression seems to be a novel prognostic biomarker in gastric cancer. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Impact of Chemotherapy on Retroperitoneal Lymph Nodes in Ovarian Cancer.

PubMed

Keyver-Paik, Mignon-Denise; Arden, Janne Myriam; Lüders, Christine; Thiesler, Thore; Abramian, Alina; Hoeller, Tobias; Hecking, Thomas; Ayub, Tiyasha Hosne; Doeser, Anna; Kaiser, Christina; Kuhn, Walther

2016-04-01

Complete cytoreduction is the most important prognostic factor in ovarian cancer. However, there exist conflicting data on whether the removal of microscopic tumor metastasis in macroscopically unsuspicious retroperitoneal lymph nodes is beneficial. Ovarian cancer tissues and tissues from lymph node metastasis of 30 patients with FIGO IIIC or IV disease undergoing neoadjuvant chemotherapy (NACT) were obtained and assessed using a validated regression score. Histopathological markers, size of largest tumor focus, and overall score were evaluated in lymph node and ovarian tissue. Regression and known prognostic factors were analyzed for influence on survival. No difference in the overall score between lymph nodes and ovarian tissue was shown, however, single parameters such as fibrosis and pattern of tumor infiltration, were significantly different. The pattern of tumor regression in lymph nodes and ovarian tissue are of prognostic value. Lymph node dissection even of unsuspicious nodes should, therefore, be performed. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Evaluation of multifunctional imaging parameters in gastro-oesophageal cancer using F-18-FDG-PET/CT with integrated perfusion CT.

PubMed

Sah, Bert-Ram; Leissing, Christian A; Delso, Gaspar; Ter Voert, Edwin E; Krieg, Stefan; Leibl, Sebastian; Schneider, Paul M; Reiner, Cäcilia S; Hüllner, Martin W; Veit-Haibach, Patrick

2018-05-10

Positron emission tomography (PET) / computed tomography (CT) is among the most frequently used imaging modalities for initial staging of gastro-oesophageal (GE) cancer, whereas CT-perfusion (CTP) provides different multiparametric information. This proof of concept study compares CTP- and PET-parameters in patients with GE cancer to evaluate correlations and a possible prognostic value of a combined PET/CTP imaging procedure. A total of 31 patients with F-18-FDG-PET/CT and CTP studies were prospectively analysed. Patients had adenocarcinoma (n = 22) and oesophageal squamous cell carcinoma (SCC, n = 9). Imaging was performed before start of treatment. CTP parameters [blood flow (BF), blood volume (BV), mean transit time (MTT)] and metabolic parameters [(maximum and mean standardised uptake values and standard deviation (SUVmax, SUVmean, SUVsd), metabolic tumour volume (MTV) and tumour lesion glycolysis (TLG)], as well as flow metabolic product [FMP (BF × SUVmax)] were determined and their relationship was compared. Additionally their association to clinical parameters (differentiation grading, staging, HER2-status, follow-up status) and to histopathological regression (post-neoadjuvant regression grading) was evaluated. Correlation between parameters of both modalities was significant between MTT and MTV (r = 0.375, p = 0.038); no other significant correlation was found. Patients with complete histopathological regression showed significantly lower BF and BV than patients with nearly complete or partial response. TLG and regression grading showed significant correlation with staging. All other quantitative parameters for CTP and PET data did not correlate significantly with histopathological regression grading, differentiation or staging. The combination of PET and CTP parameters (FMP) showed no significant prognostic value. Significant correlations were only found between MTT and MTV, which indicates a possible perfusional/metabolic coupling. Therefore, pre-therapeutic CTP and PET- parameters provide complementary information about the pre-therapeutic tumour status and are not interchangeable. Only CTP parameters might be able to predict complete histopathological regression. On the other hand, only PET parameters are correlated with staging.

Prognostic Significance of Carbohydrate Antigen 19-9 in Unresectable Locally Advanced Pancreatic Cancer Treated With Dose-Escalated Intensity Modulated Radiation Therapy and Concurrent Full-Dose Gemcitabine: Analysis of a Prospective Phase 1/2 Dose Escalation Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vainshtein, Jeffrey M., E-mail: jvainsh@med.umich.edu; Schipper, Matthew; Zalupski, Mark M.

2013-05-01

Purpose: Although established in the postresection setting, the prognostic value of carbohydrate antigen 19-9 (CA19-9) in unresectable locally advanced pancreatic cancer (LAPC) is less clear. We examined the prognostic utility of CA19-9 in patients with unresectable LAPC treated on a prospective trial of intensity modulated radiation therapy (IMRT) dose escalation with concurrent gemcitabine. Methods and Materials: Forty-six patients with unresectable LAPC were treated at the University of Michigan on a phase 1/2 trial of IMRT dose escalation with concurrent gemcitabine. CA19-9 was obtained at baseline and during routine follow-up. Cox models were used to assess the effect of baseline factorsmore » on freedom from local progression (FFLP), distant progression (FFDP), progression-free survival (PFS), and overall survival (OS). Stepwise forward regression was used to build multivariate predictive models for each endpoint. Results: Thirty-eight patients were eligible for the present analysis. On univariate analysis, baseline CA19-9 and age predicted OS, CA19-9 at baseline and 3 months predicted PFS, gross tumor volume (GTV) and black race predicted FFLP, and CA19-9 at 3 months predicted FFDP. On stepwise multivariate regression modeling, baseline CA19-9, age, and female sex predicted OS; baseline CA19-9 and female sex predicted both PFS and FFDP; and GTV predicted FFLP. Patients with baseline CA19-9 ≤90 U/mL had improved OS (median 23.0 vs 11.1 months, HR 2.88, P<.01) and PFS (14.4 vs 7.0 months, HR 3.61, P=.001). CA19-9 progression over 90 U/mL was prognostic for both OS (HR 3.65, P=.001) and PFS (HR 3.04, P=.001), and it was a stronger predictor of death than either local progression (HR 1.46, P=.42) or distant progression (HR 3.31, P=.004). Conclusions: In patients with unresectable LAPC undergoing definitive chemoradiation therapy, baseline CA19-9 was independently prognostic even after established prognostic factors were controlled for, whereas CA19-9 progression strongly predicted disease progression and death. Future trials should stratify by baseline CA19-9 and incorporate CA19-9 progression as a criterion for progressive disease.« less

Kinematic parameters of second-mode internal waves in the South China Sea

NASA Astrophysics Data System (ADS)

Kurkina, Oxana; Talipova, Tatiana; Kurkin, Andrey; Naumov, Alexander; Rybin, Artem

2017-04-01

Kinematic parameters of second-mode internal waves (in the framework of weakly nonlinear model of the Gardner equation) are calculated for the region of the South China Sea on a base of GDEM climatology. The prognostic parameters of the model include phase speed of long linear waves, coefficients of dispersion, quadratic and cubic nonlinearity, location (in vertical) of minimum, zero and maximum of the second vertical baroclinic mode and the ratio of its maximal and minimal values. All the parameters are presented in the form of geographical maps for winter (January) and summer (July) seasons. Frequence (in the sense of occurrence) histograms and scatter plots with depth are also given for all the parameters. Special attention is paid to the conditions of normalizing for internal waves of the second mode, as it possesses two extremes. Here some freedom exists, but for correct further modeling of internal waves within the Gardner model one has to fix and keep the same normalization (at maximum or at minimum) for whole a basin. Constructed arrays of prognostic parameters of second-mode internal waves are necessary for the estimations of shape and width (at fixed amplitude) of internal solitary and breather-like waves, limiting amplitudes of internal solitary waves of different families, for assessment of near-bed and near-surface flows induced by such waves, and for evaluation of transport distance for dissolved and suspended matter. The presented results of research are obtained with the support of the Russian Foundation for Basic Research grant 16-05-00049.

The political uses of astrology: predicting the illness and death of princes, kings and popes in the Italian Renaissance.

PubMed

Azzolini, Monica

2010-06-01

This paper examines the production and circulation of astrological prognostications regarding the illness and death of kings, princes, and popes in the Italian Renaissance (ca. 1470-1630). The distribution and consumption of this type of astrological information was often closely linked to the specific political situation in which they were produced. Depending on the astrological techniques used (prorogations, interrogations, or annual revolutions), and the media in which they appeared (private letters or printed prognostica) these prognostications fulfilled different functions in the information economy of Renaissance Italy. Some were used to legitimise the rule of a political leader, others to do just the opposite. Astrological prorogations and interrogations were often used to plan military and political strategies in case of the illness or death of a political leader, while astrological prognostications were generally written to promote certain political leaders while undermining others. While certainly often partisan to this game, astrologers, for their part, worked within a very well established tradition that gave authority to their forecasts. This paper argues that, as indicators of deeper political tensions otherwise not always explicitly manifest, these prognostications are privileged sources of information providing a better understanding of the political history of the period.

Prognostic and predictive factors in colorectal cancer.

PubMed

Bolocan, A; Ion, D; Ciocan, D N; Paduraru, D N

2012-01-01

Colorectal cancer (CRC) is an important public health problem; it is a leading cause of cancer mortality in the industrialized world, second to lung cancer: each year there are nearly one million new cases of CRC diagnosed worldwide and half a million deaths (1). This review aims to summarise the most important currently available markers for CRC that provide prognostic or predictive information. Amongst others, it covers serum markers such as CEA and CA19-9, markers expressed by tumour tissues, such as thymidylate synthase, and also the expression/loss of expression of certain oncogenes and tumour suppressor genes such as K-ras and p53. The prognostic value of genomic instability, angiogenesis and proliferative indices, such as the apoptotic index, are discussed. The advent of new therapies created the pathway for a personalized approach of the patient. This will take into consideration the complex genetic mechanisms involved in tumorigenesis, besides the classical clinical and pathological stagings. The growing number of therapeutic agents and known molecular targets in oncology lead to a compulsory study of the clinical use of biomarkers with role in improving response and survival, as well as in reducing toxicity and establishing economic stability. The potential predictive and prognostic biomarkers which have arisen from the study of the genetic basis of colorectal cancer and their therapeutical significance are discussed. RevistaChirurgia.

The Role of the 21-Gene Recurrence Score in Breast Cancer Treatment.

PubMed

Ethier, Josee-Lyne; Amir, Eitan

2016-08-01

Several multi-gene assays have been developed to predict the risk of recurrence in patients with estrogen receptor-positive early breast cancer and in whom endocrine therapy is planned. The 21-gene assay is widely used and its prognostic value has been retrospectively validated, showing significant differences in the risk of distant recurrence for patients at high versus low risk. Its role in predicting chemotherapy benefit has also been established, showing a clear benefit for high-risk patients and minimal benefit in those at low risk. These findings have been prospectively investigated in TAILORx (Trial Assigning Individualized Options for Treatment), where available data from the low-risk cohort confirms the prognostic value of this diagnostic test. The prognostic utility of the 21-gene assay increases when combined with clinicopathologic variables, and data from integrated models suggest that its use should be limited to patients with tumor characteristics suggestive of potential chemotherapy benefit. Furthermore, the 21-gene assay has been shown to impact clinical decision making in a cost-effective manner, although direct evidence of benefit from modified treatment recommendations is yet to be proven. The prognostic value of this test has also been shown in populations with node-positive or locally advanced disease treated with neoadjuvant chemotherapy, and ongoing trials aim to prospectively validate these findings.

Long-term outcome in patients with short bowel syndrome after longitudinal intestinal lengthening and tailoring.

PubMed

Reinshagen, K; Kabs, C; Wirth, H; Hable, N; Brade, J; Zahn, K; Hagl, C; Jester, I; Waag, K L

2008-11-01

Longitudinal intestinal lengthening and tailoring (LILT) is a well-established surgical treatment for short bowel syndrome. It has been shown to enhance peristalsis, decrease bacterial overgrowth, and extend mucosal contact time for nutrients. We present the results of a long-term follow-up of patients who underwent LILT and define prognostic parameters for the survival of these patients. Between 1987 and 2006, 53 patients underwent LILT in our institution. The main diagnoses were gastroschisis, intestinal volvulus, intestinal atresias, and necrotizing enterocolitis. LILT was performed at a mean age of 24 months (range 4144 months). The follow-up time was 79.76 months (range 6234 months). After LILT, 41 of 53 patients survived, and 36 of 41 surviving patients were successfully weaned from parenteral nutrition (PN). In long-term follow-up 79% stayed free of PN. The overall survival rate was 77.36%. Weight gain occurred in 58% of the patients after LILT. The quality of life after LILT is on a high level, with most patients having normal physical strength and participating in normal social life and education. Prognostic factors for survival after LILT in short bowel syndrome are length of small intestine (0.06582 + 0.0131 x bowel cm), length of large bowel (P = 0.039), preoperative liver function, and successful weaning from PN within 18 months postoperatively (P = 0.0032). Patients undergoing LILT in short bowel syndrome have a high survival rate, weight gain, and a high quality of life. Autologous gastrointestinal reconstruction remains therefore the first choice in the treatment of patients with short bowel syndrome.

Seizures and the natural history of World Health Organization Grade II gliomas: a review.

PubMed

Smits, Anja; Duffau, Hugues

2011-05-01

The majority of adults with low-grade gliomas have seizures. Despite the frequency of seizures as initial symptoms and symptoms of later disease, seizures in relation to the natural course of low-grade gliomas have received little attention. In this review, we provide an update of the literature on the prognostic impact of preoperative seizures and discuss the tumor- and treatment-related factors affecting seizure control at later stages of the disease. Seizures occur most frequently at disease presentation and predict a more favorable outcome. Initial seizures are correlated with tumor location and possibly indirectly to the molecular profile of the tumor. About 50% of all patients with seizures at presentation continue to have seizures before surgery. Maximal tumor resection, including resection of epileptic foci, is a valuable strategy for improving seizure control. In addition, radiotherapy and chemotherapy, as single therapies or in combination with surgery, have shown beneficial effects in terms of seizure reduction. Recurrent seizures after macroscopically complete tumor resection may be a marker for accelerated tumor growth. Recurrent seizures after an initial transient stabilization after radiotherapy and/or chemotherapy may be a marker for anaplastic tumor transformation. Preoperative seizures likely reflect, apart from tumor location, intrinsic tumor properties as well. Change in seizure control in individual patients is frequently associated with altered tumor behavior. Including seizures and seizure control as clinical parameters is recommended in future trials of low-grade gliomas to further establish the prognostic value of these symptoms and to identify the factors affecting seizure control.

[Immunoglobulin genes and T-cell receptors as molecular markers in children with acute lymphoblastic leukaemia].

PubMed

Lazić, Jelena; Dokmanović, Lidija; Krstovski, Nada; Predojević, Jelica; Tosić, Natasa; Pavlović, Sonja; Janić, Dragana

2009-01-01

Acute lymphoblastic leukaemia (ALL) is a malignant clonal disease, one of the most common malignancies in childhood. Contemporary protocols ensure high remission rate and long term free survival. The ability of molecular genetic methods help to establish submicroscopic classification and minimal residual disease (MRD) follow up, in major percent responsible for relapse. The aim of the study was to detect the frequency of IgH and TCR gene rearrangements and their correlation with clinical parameters. Forty-one children with ALL were enrolled in the study group, with initial diagnosis of IgH and TCR gene rearrangements by polimerase chain reaction (PCR). MRD follow-up was performed in induction phase when morphological remission was expected, and after intensive chemiotherapy. In the study group IgH rearrangement was detected in 82.9% of children at the diagnosis, while TCR rearrangement was seen in 56.1%. On induction day 33, clonal IgH rearrangements persisted in 39% and TCR rearrangements in 36.5% of children. Molecular analysis of genetic alterations and their correlation with standard prognostic parameters show the importance of risk stratification revision which leads to new therapy intensification approach. MRD stands out as a precise predictive factor for the relapse of disease.

Hypotheses, rationale, design, and methods for prognostic evaluation of cardiac biomarker elevation after percutaneous and surgical revascularization in the absence of manifest myocardial infarction. A comparative analysis of biomarkers and cardiac magnetic resonance. The MASS-V Trial.

PubMed

Hueb, Whady; Gersh, Bernard J; Rezende, Paulo Cury; Garzillo, Cibele Larrosa; Lima, Eduardo Gomes; Vieira, Ricardo D'Oliveira; Garcia, Rosa Maria Rahmi; Favarato, Desiderio; Segre, Carlos Alexandre W; Pereira, Alexandre Costa; Soares, Paulo Rogério; Ribeiro, Expedito; Lemos, Pedro; Perin, Marco A; Strunz, Célia Cassaro; Dallan, Luis A O; Jatene, Fabio B; Stolf, Noedir A G; Hueb, Alexandre Ciappina; Dias, Ricardo; Gaiotto, Fabio A; da Costa, Leandro Menezes Alves; Oikawa, Fernando Teiichi Costa; de Melo, Rodrigo Morel Vieira; Serrano, Carlos Vicente; de Ávila, Luiz Francisco Rodrigues; Villa, Alexandre Volney; Filho, José Rodrigues Parga; Nomura, César; Ramires, José A F; Kalil Filho, Roberto

2012-08-16

Although the release of cardiac biomarkers after percutaneous (PCI) or surgical revascularization (CABG) is common, its prognostic significance is not known. Questions remain about the mechanisms and degree of correlation between the release, the volume of myocardial tissue loss, and the long-term significance. Delayed-enhancement of cardiac magnetic resonance (CMR) consistently quantifies areas of irreversible myocardial injury. To investigate the quantitative relationship between irreversible injury and cardiac biomarkers, we will evaluate the extent of irreversible injury in patients undergoing PCI and CABG and relate it to postprocedural modifications in cardiac biomarkers and long-term prognosis. The study will include 150 patients with multivessel coronary artery disease (CAD) with left ventricle ejection fraction (LVEF) and a formal indication for CABG; 50 patients will undergo CABG with cardiopulmonary bypass (CPB); 50 patients with the same arterial and ventricular condition indicated for myocardial revascularization will undergo CABG without CPB; and another 50 patients with CAD and preserved ventricular function will undergo PCI using stents. All patients will undergo CMR before and after surgery or PCI. We will also evaluate the release of cardiac markers of necrosis immediately before and after each procedure. Primary outcome considered is overall death in a 5-year follow-up. Secondary outcomes are levels of CK-MB isoenzyme and I-Troponin in association with presence of myocardial fibrosis and systolic left ventricle dysfunction assessed by CMR. The MASS-V Trial aims to establish reliable values for parameters of enzyme markers of myocardial necrosis in the absence of manifest myocardial infarction after mechanical interventions. The establishments of these indices have diagnostic value and clinical prognosis and therefore require relevant and different therapeutic measures. In daily practice, the inappropriate use of these necrosis markers has led to misdiagnosis and therefore wrong treatment. The appearance of a more sensitive tool such as CMR provides an unprecedented diagnostic accuracy of myocardial damage when correlated with necrosis enzyme markers. We aim to correlate laboratory data with imaging, thereby establishing more refined data on the presence or absence of irreversible myocardial injury after the procedure, either percutaneous or surgical, and this, with or without the use of cardiopulmonary bypass.

Liver transplantation for hepatocellular carcinoma: a proposal of a prognostic scoring system.

PubMed

Iwatsuki, S; Dvorchik, I; Marsh, J W; Madariaga, J R; Carr, B; Fung, J J; Starzl, T E

2000-10-01

The current staging system of hepatocellular carcinoma established by the International Union Against Cancer and the American Joint Committee on Cancer does not necessarily predict the outcomes after hepatic resection or transplantation. Various clinical and pathologic risk factors for tumor recurrence were examined on 344 consecutive patients who received hepatic transplantation in the presence of nonfibrolamellar hepatocellular carcinoma to establish a reliable risk scoring system. Multivariate analysis identified three factors as independently significant poor prognosticators: 1) bilobarly distributed tumors, 2) size of the greatest tumor (2 to 5 cm and > 5 cm), and 3) vascular invasion (microscopic and macroscopic). Prognostic risk score (PRS) of each patient was calculated from the relative risks of multivariate analysis. The patients were grouped into five grades of tumor recurrence risk: grade 1: PRS = 0 to < 7.5; grade 2: PRS = 7.5 to < or = 11.0; grade 3: PRS > 11.0 to 15.0; grade 4: PRS > or = 15.0; and grade 5: positive node, metastasis, or margin. The proposed PRS system correlated extremely well with tumor-free survival after liver transplantation (100%, 61%, 40%, 5%, and 0%, from grades 1 to 5, respectively, at 5 years), but current pTNM staging did not. 1) Patients with grades 1 and 2 are effectively treated with liver transplantation, 2) patients with grades 4 and 5 are poor candidates for liver transplantation, and 3) patients with grade 1 do not benefit from adjuvant chemotherapy.

Development and external validation of nomograms to predict the risk of skeletal metastasis at the time of diagnosis and skeletal metastasis-free survival in nasopharyngeal carcinoma.

PubMed

Yang, Lin; Xia, Liangping; Wang, Yan; He, Shasha; Chen, Haiyang; Liang, Shaobo; Peng, Peijian; Hong, Shaodong; Chen, Yong

2017-09-06

The skeletal system is the most common site of distant metastasis in nasopharyngeal carcinoma (NPC); various prognostic factors have been reported for skeletal metastasis, though most studies have focused on a single factor. We aimed to establish nomograms to effectively predict skeletal metastasis at initial diagnosis (SMAD) and skeletal metastasis-free survival (SMFS) in NPC. A total of 2685 patients with NPC who received bone scintigraphy (BS) and/or 18F-deoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) and 2496 patients without skeletal metastasis were retrospectively assessed to develop individual nomograms for SMAD and SMFS. The models were validated externally using separate cohorts of 1329 and 1231 patients treated at two other institutions. Five independent prognostic factors were included in each nomogram. The SMAD nomogram had a significantly higher c-index than the TNM staging system (training cohort, P = 0.005; validation cohort, P < 0.001). The SMFS nomogram had significantly higher c-index values in the training and validation sets than the TNM staging system (P < 0.001 and P = 0.005, respectively). Three proposed risk stratification groups were created using the nomograms, and enabled significant discrimination of SMFS for each risk group. The prognostic nomograms established in this study enable accurate stratification of distinct risk groups for skeletal metastasis, which may improve counseling and facilitate individualized management of patients with NPC.

Prognostic value of the pretreatment neutrophil-to-lymphocyte ratio in cervical cancer: a meta-analysis and systematic review.

PubMed

Wu, Jiayuan; Chen, Manyu; Liang, Caixia; Su, Wenmei

2017-02-21

The prognostic value of pretreatment neutrophil-to-lymphocyte ratio (NLR) in cervical cancer remains controversial. We conducted a meta-analysis based on the data from 13 studies with 3729 patients to evaluate the association between the pretreatment NLR and the clinical outcomes of overall survival and progression-free survival in patients with cervical cancer. The relationship between NLR and clinicopathological parameters was also assessed. Hazard ratio (HR) or odds ratio (OR) with its 95% confidence interval (CI) was used as the effect size estimate. Our analysis indicated that elevated pretreatment NLR was a poor prognostic marker for patients with cervical cancer because it predicted unfavorable overall survival (HR = 1.375, 95% CI: 1.200-1.576) and progression-free survival (HR = 1.646, 95% CI: 1.313-2.065). Increased NLR is also significantly associated with the larger tumor size (OR = 1.780, 95% CI: 1.090-2.908), advanced clinical stage (OR = 2.443, 95% CI: 1.730-3.451), and positive lymph node metastasis (OR = 2.380, 95% CI: 1.775-3.190). By these results, high pretreatment NLR predicted a shorter survival period for patients with cervical cancer, and it could be served as a novel index of prognostic evaluation in patients with cervical cancer.

Nuclear YB-1 expression as a negative prognostic marker in nonsmall cell lung cancer.

PubMed

Gessner, C; Woischwill, C; Schumacher, A; Liebers, U; Kuhn, H; Stiehl, P; Jürchott, K; Royer, H D; Witt, C; Wolff, G

2004-01-01

The human Y-box binding protein, YB-1, is a multifunctional protein that regulates gene expression. Nuclear expression of YB-1 has been associated with chemoresistance and poor prognosis of tumour patients. Representative samples from autopsied material of primary tumours from 77 patients with NSCLC were investigated by immunohistochemistry for subcellular distribution of YB-1 and p53, in order to evaluate the prognostic role of nuclear expression of YB-1. Cytoplasmic YB-1 expression was found in all tumour samples, whereas nuclear expression was only observed in 48%. There was no correlation with histological classification, clinical parameters or tumour size, stage and metastasis status. However, patients with positive nuclear YB-1 expression in tumours showed reduced survival times when compared with patients without nuclear expression. Including information about the histology and mutational status for p53 increased the prognostic value of nuclear YB-1. Patients with nuclear YB-1 expression and p53 mutations had the worst prognosis (median survival 3 months), while best outcome was found in patients with no nuclear YB-1 and wildtype p53 (median survival 15 months). This suggests that the combined analysis of both markers allows a better identification of subgroups with varying prognosis. Nuclear expression of Y-box binding protien seems to be an independent prognostic marker.

Chromosomal aberrations and their prognostic value in a series of 174 untreated patients with Waldenström's macroglobulinemia

PubMed Central

Nguyen-Khac, Florence; Lambert, Jerome; Chapiro, Elise; Grelier, Aurore; Mould, Sarah; Barin, Carole; Daudignon, Agnes; Gachard, Nathalie; Struski, Stéphanie; Henry, Catherine; Penther, Dominique; Mossafa, Hossein; Andrieux, Joris; Eclache, Virginie; Bilhou-Nabera, Chrystèle; Luquet, Isabelle; Terre, Christine; Baranger, Laurence; Mugneret, Francine; Chiesa, Jean; Mozziconacci, Marie-Joelle; Callet-Bauchu, Evelyne; Veronese, Lauren; Blons, Hélène; Owen, Roger; Lejeune, Julie; Chevret, Sylvie; Merle-Beral, Hélène; Leblondon, Véronique

2013-01-01

Waldenström's macroglobulinemia is a disease of mature B cells, the genetic basis of which is poorly understood. Few recurrent chromosomal abnormalities have been reported, and their prognostic value is not known. We conducted a prospective cytogenetic study of Waldenström's macroglobulinemia and examined the prognostic value of chromosomal aberrations in an international randomized trial. The main aberrations were 6q deletions (30%), trisomy 18 (15%), 13q deletions (13%), 17p (TP53) deletions (8%), trisomy 4 (8%), and 11q (ATM) deletions (7%). There was a significant association between trisomy of chromosome 4 and trisomy of chromosome 18. Translocations involving the IGH genes were rare (<5%). Deletion of 6q and 11q, and trisomy 4, were significantly associated with adverse clinical and biological parameters. Patients with TP53 deletion had short progression-free survival and short disease-free survival. Although rare (<5%), trisomy 12 was associated with short progression-free survival. In conclusion, the cytogenetic profile of Waldenström's macroglobulinemia appears to differ from that of other B-cell lymphomas. Chromosomal abnormalities may help with diagnosis and prognostication, in conjunction with other clinical and biological characteristics. This trial is registered with Clinicaltrials.gov, numbers NCT00566332 and NCT00608374. PMID:23065509

Expression and prognostic examination of heat shock proteins (HSP 27, HSP 70, and HSP 90) in medulloblastoma.

PubMed

Hauser, Péter; Hanzély, Zoltán; Jakab, Zsuzsanna; Oláh, Lászlóné; Szabó, Erika; Jeney, András; Schuler, Dezso; Fekete, Gyoörgy; Bognár, László; Garami, Miklós

2006-07-01

Expression of heat shock proteins (HSPs) is of prognostic significance in several tumor types. HSP expression levels were determined in medulloblastomas and tested whether HSPs expression was associated with prognostic parameters. Expression of antiapoptotic HSP 27, HSP 70, and HSP 90 was investigated by immunohistochemistry, on paraffin-embedded sections from 65 patients. Expression of HSPs was validated on internal vascular controls and by Western blotting analysis. Sample evaluation was based on the estimated percentage of HSP positive tumor cells. For survival analysis Kaplan-Meier method, for statistical analysis chi2 test, univariate analysis, and log rank test were applied. Expression of HSPs varied in medulloblastomas. On the basis of the average expression rate of HSPs, at HSP 27 and HSP 90 with a 10% cut off, and at HSP 70 with a 70% cut off 2 groups were created. The amount of expression of any of the HSP types was not significantly associated with known prognostic factors (age of patient, extent of resection, presence of metastasis) and histologic subtype. After an average follow-up period of 4.30 years, no significant difference was observed in survival depending on the expression of HSP 27 or HSP 70 or HSP 90. The high expression of HSPs indicates that these proteins are potential therapeutic targets.

Ovarian stimulation length, number of follicles higher than 17 mm and estradiol on the day of human chorionic gonadotropin administration are risk factors for multiple pregnancy in intrauterine insemination

PubMed Central

MELO, MARCO A.B.; SIMÓN, CARLOS; REMOHÍ, JOSÉ; PELLICER, ANTONIO; MESEGUER, MARCOS

2007-01-01

Aim:  The aim of the present study was to identify the risk factors, their prognostic value on multiple pregnancies (MP) prediction and their thresholds in women undergoing controlled ovarian hyperstimulation (COH) with follicle stimulating hormone (FSH) and intrauterine insemination (IUI). Methods:  A case‐control study was carried out by identifying in our database all the pregnancies reached by donor and conjugal IUI (DIUI and CIUI, respectively), and compared cycle features, patients’ characteristics and sperm analysis results between women achieving single pregnancy (SP) versus MP. The number of gestational sacs, follicular sizes and estradiol levels on the human chorionic gonadotropin (hCG) administration day, COH length and semen parameters were obtained from each cycle and compared. Student's t‐tests for mean comparisons, receiver–operator curve (ROC) analysis to determine the predictive value of each parameter on MP achievement and multiple regression analysis to determine single parameter influence were carried out. Results:  Women with MP in IUI stimulated cycles reached the adequate size of the dominant follicle (17 mm) significantly earlier than those achieving SP. Also, the mean follicles number, and estradiol levels on the hCG day were higher in the CIUI and DIUI MP group. Nevertheless, only ROC curve analysis revealed good prognostic value for estradiol and follicles higher than 17 mm. Multiple regression analysis confirmed these results. No feature of the basic sperm analysis, either in the ejaculate or in the prepared sample, was different or predictive of MP. When using donor sperm, different thresholds of follicle number, stimulation length and estradiol in the prediction of MP were noted, in comparison with CIUI. Conclusions:  MP in stimulated IUI cycles are closely associated to stimulation length, number of developed follicles higher than 17 mm on the day of hCG administration and estradiol levels. Also, estradiol has a good predictive value over MP in IUI stimulated cycles. The establishment of clinical thresholds will certainly help in the management of these couples to avoid undesired multiple pregnancies by canceling cycles or converting them into in vitro fertilization procedures. (Reprod Med Biol 2007; 6: 19–26) PMID:29699262

Establishment of an Adjusted Prognosis Analysis Model for Initially Diagnosed Non-Small-Cell Lung Cancer With Brain Metastases From Sun Yat-Sen University Cancer Center.

PubMed

Dinglin, Xiao-Xiao; Ma, Shu-Xiang; Wang, Fang; Li, De-Lan; Liang, Jian-Zhong; Chen, Xin-Ru; Liu, Qing; Zeng, Yin-Duo; Chen, Li-Kun

2017-05-01

The current published prognosis models for brain metastases (BMs) from cancer have not addressed the issue of either newly diagnosed non-small-cell lung cancer (NSCLC) with BMs or the lung cancer genotype. We sought to build an adjusted prognosis analysis (APA) model, a new prognosis model specifically for NSCLC patients with BMs at the initial diagnosis using adjusted prognosis analysis (APA). The model was derived using data from 1158 consecutive patients, with 837 in the derivation cohort and 321 in the validation cohort. The patients had initially received a diagnosis of BMs from NSCLC at Sun Yat-Sen University Cancer Center from 1994 to 2015. The prognostic factors analyzed included patient characteristics, disease characteristics, and treatments. The APA model was built according to the numerical score derived from the hazard ratio of each independent prognostic variable. The predictive accuracy of the APA model was determined using a concordance index and was compared with current prognosis models. The results were validated using bootstrap resampling and a validation cohort. We established 2 prognostic models (APA 1 and 2) for the whole group of patients and for those with known epidermal growth factor receptor (EGFR) genotype, respectively. Six factors were independently associated with survival time: Karnofsky performance status, age, smoking history (replaced by EGFR mutation in APA 2), local treatment of intracranial metastases, EGFR-tyrosine kinase inhibitor treatment, and chemotherapy. Patients in the derivation cohort were stratified into low- (score, 0-2), moderate- (score, 3-5), and high-risk (score 6-7) groups according to the median survival time (16.6, 10.3, and 5.2 months, respectively; P < .001). The results were further confirmed in the validation cohort. Compared with recursive partition analysis and graded prognostic assessment, APA seems to be more suitable for initially diagnosed NSCLC with BMs. Copyright © 2017 Elsevier Inc. All rights reserved.

Automatic selection of optimal Savitzky-Golay filter parameters for Coronary Wave Intensity Analysis.

PubMed

Rivolo, Simone; Nagel, Eike; Smith, Nicolas P; Lee, Jack

2014-01-01

Coronary Wave Intensity Analysis (cWIA) is a technique capable of separating the effects of proximal arterial haemodynamics from cardiac mechanics. The cWIA ability to establish a mechanistic link between coronary haemodynamics measurements and the underlying pathophysiology has been widely demonstrated. Moreover, the prognostic value of a cWIA-derived metric has been recently proved. However, the clinical application of cWIA has been hindered due to the strong dependence on the practitioners, mainly ascribable to the cWIA-derived indices sensitivity to the pre-processing parameters. Specifically, as recently demonstrated, the cWIA-derived metrics are strongly sensitive to the Savitzky-Golay (S-G) filter, typically used to smooth the acquired traces. This is mainly due to the inability of the S-G filter to deal with the different timescale features present in the measured waveforms. Therefore, we propose to apply an adaptive S-G algorithm that automatically selects pointwise the optimal filter parameters. The newly proposed algorithm accuracy is assessed against a cWIA gold standard, provided by a newly developed in-silico cWIA modelling framework, when physiological noise is added to the simulated traces. The adaptive S-G algorithm, when used to automatically select the polynomial degree of the S-G filter, provides satisfactory results with ≤ 10% error for all the metrics through all the levels of noise tested. Therefore, the newly proposed method makes cWIA fully automatic and independent from the practitioners, opening the possibility to multi-centre trials.

A novel scoring system for gastric cancer risk assessment based on the expression of three CLIP4 DNA methylation-associated genes

PubMed Central

Hu, Chenggong; Zhou, Yongfang; Liu, Chang; Kang, Yan

2018-01-01

Gastric cancer (GC) is the fifth most common cancer and the third leading cause of cancer-associated mortality worldwide. In the current study, comprehensive bioinformatic analyses were performed to develop a novel scoring system for GC risk assessment based on CAP-Gly domain containing linker protein family member 4 (CLIP4) DNA methylation status. Two GC datasets with methylation sequencing information and mRNA expression profiling were downloaded from the The Cancer Genome Atlas and Gene Expression Omnibus databases. Differentially expressed genes (DEGs) between the CLIP4 hypermethylation and CLIP4 hypomethylation groups were screened using the limma package in R 3.3.1, and survival analysis of these DEGs was performed using the survival package. A risk scoring system was established via regression factor-weighted gene expression based on linear combination to screen the most important genes associated with CLIP4 methylation and prognosis. Genes associated with high/low-risk value were selected using the limma package. Functional enrichment analysis of the top 500 DEGs that positively and negatively associated with risk values was performed using DAVID 6.8 online and the gene set enrichment analysis (GSEA) software. In total, 35 genes were identified to be that significantly associated with prognosis and CLIP4 DNA methylation, and three prognostic signature genes, claudin-11 (CLDN11), apolipoprotein D (APOD), and chordin like 1 (CHRDL1), were used to establish a risk assessment system. The prognostic scoring system exhibited efficiency in classifying patients with different prognoses, where the low-risk groups had significantly longer overall survival times than those in the high-risk groups. CLDN11, APOD and CHRDL1 exhibited reduced expression in the hypermethylation and low-risk groups compare with the hypomethylation and high-risk groups, respectively. Multivariate Cox analysis indicated that risk value could be used as an independent prognostic factor. In functional analysis, six functional gene ontology terms and five GSEA pathways were associated with CLDN11, APOD and CHRDL1. The results established the credibility of the scoring system in this study. Additionally, these three genes, which were significantly associated with CLIP4 DNA methylation and GC risk assessment, were identified as potential prognostic biomarkers. PMID:29901187

TU-F-12A-05: Sensitivity of Textural Features to 3D Vs. 4D FDG-PET/CT Imaging in NSCLC Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, F; Nyflot, M; Bowen, S

2014-06-15

Purpose: Neighborhood Gray-level difference matrices (NGLDM) based texture parameters extracted from conventional (3D) 18F-FDG PET scans in patients with NSCLC have been previously shown to associate with response to chemoradiation and poorer patient outcome. However, the change in these parameters when utilizing respiratory-correlated (4D) FDG-PET scans has not yet been characterized for NSCLC. The Objectives: of this study was to assess the extent to which NGLDM-based texture parameters on 4D PET images vary with reference to values derived from 3D scans in NSCLC. Methods: Eight patients with newly diagnosed NSCLC treated with concomitant chemoradiotherapy were included in this study. 4Dmore » PET scans were reconstructed with OSEM-IR in 5 respiratory phase-binned images and corresponding CT data of each phase were employed for attenuation correction. NGLDM-based texture features, consisting of coarseness, contrast, busyness, complexity and strength, were evaluated for gross tumor volumes defined on 3D/4D PET scans by radiation oncologists. Variation of the obtained texture parameters over the respiratory cycle were examined with respect to values extracted from 3D scans. Results: Differences between texture parameters derived from 4D scans at different respiratory phases and those extracted from 3D scans ranged from −30% to 13% for coarseness, −12% to 40% for contrast, −5% to 50% for busyness, −7% to 38% for complexity, and −43% to 20% for strength. Furthermore, no evident correlations were observed between respiratory phase and 4D scan texture parameters. Conclusion: Results of the current study showed that NGLDM-based texture parameters varied considerably based on choice of 3D PET and 4D PET reconstruction of NSCLC patient images, indicating that standardized image acquisition and analysis protocols need to be established for clinical studies, especially multicenter clinical trials, intending to validate prognostic values of texture features for NSCLC.« less

Tumor Mutational Load and Immune Parameters across Metastatic Renal Cell Carcinoma Risk Groups.

PubMed

de Velasco, Guillermo; Miao, Diana; Voss, Martin H; Hakimi, A Ari; Hsieh, James J; Tannir, Nizar M; Tamboli, Pheroze; Appleman, Leonard J; Rathmell, W Kimryn; Van Allen, Eliezer M; Choueiri, Toni K

2016-10-01

Patients with metastatic renal cell carcinoma (mRCC) have better overall survival when treated with nivolumab, a cancer immunotherapy that targets the immune checkpoint inhibitor programmed cell death 1 (PD-1), rather than everolimus (a chemical inhibitor of mTOR and immunosuppressant). Poor-risk mRCC patients treated with nivolumab seemed to experience the greatest overall survival benefit, compared with patients with favorable or intermediate risk, in an analysis of the CheckMate-025 trial subgroup of the Memorial Sloan Kettering Cancer Center (MSKCC) prognostic risk groups. Here, we explore whether tumor mutational load and RNA expression of specific immune parameters could be segregated by prognostic MSKCC risk strata and explain the survival seen in the poor-risk group. We queried whole-exome transcriptome data in renal cell carcinoma patients (n = 54) included in The Cancer Genome Atlas who ultimately developed metastatic disease or were diagnosed with metastatic disease at presentation and did not receive immune checkpoint inhibitors. Nonsynonymous mutational load did not differ significantly by the MSKCC risk group, nor was the expression of cytolytic genes-granzyme A and perforin-or selected immune checkpoint molecules different across MSKCC risk groups. In conclusion, this analysis revealed that mutational load and expression of markers of an active tumor microenvironment did not correlate with MSKCC risk prognostic classification in mRCC. Cancer Immunol Res; 4(10); 820-2. ©2016 AACR. ©2016 American Association for Cancer Research.

Randomization in clinical trials: stratification or minimization? The HERMES free simulation software.

PubMed

Fron Chabouis, Hélène; Chabouis, Francis; Gillaizeau, Florence; Durieux, Pierre; Chatellier, Gilles; Ruse, N Dorin; Attal, Jean-Pierre

2014-01-01

Operative clinical trials are often small and open-label. Randomization is therefore very important. Stratification and minimization are two randomization options in such trials. The first aim of this study was to compare stratification and minimization in terms of predictability and balance in order to help investigators choose the most appropriate allocation method. Our second aim was to evaluate the influence of various parameters on the performance of these techniques. The created software generated patients according to chosen trial parameters (e.g., number of important prognostic factors, number of operators or centers, etc.) and computed predictability and balance indicators for several stratification and minimization methods over a given number of simulations. Block size and proportion of random allocations could be chosen. A reference trial was chosen (50 patients, 1 prognostic factor, and 2 operators) and eight other trials derived from this reference trial were modeled. Predictability and balance indicators were calculated from 10,000 simulations per trial. Minimization performed better with complex trials (e.g., smaller sample size, increasing number of prognostic factors, and operators); stratification imbalance increased when the number of strata increased. An inverse correlation between imbalance and predictability was observed. A compromise between predictability and imbalance still has to be found by the investigator but our software (HERMES) gives concrete reasons for choosing between stratification and minimization; it can be downloaded free of charge. This software will help investigators choose the appropriate randomization method in future two-arm trials.

Salvage high-intensity focused ultrasound ablation for prostate cancer local recurrence after external-beam radiation therapy: prognostic value of prostate MRI.

PubMed

Rouvière, O; Sbihi, L; Gelet, A; Chapelon, J-Y

2013-07-01

To assess the prognostic value of magnetic resonance imaging (MRI) before salvage high-intensity focused ultrasound (HIFU) for locally recurrent prostate cancer after external-beam radiotherapy (EBRT). Forty-six patients who underwent prostate MRI before salvage HIFU for locally recurrent prostate cancer after EBRT were retrospectively studied. HIFU failure was defined as a prostate-specific antigen (PSA) value >nadir + 2 ng/ml (Phoenix criteria) or positive follow-up biopsy or initiation of any other salvage therapy. The following prognostic parameters were assessed: neoadjuvant hormone therapy, clinical stage and Gleason score of recurrence, PSA level and velocity at HIFU treatment, and six MRI-derived parameters (prostate volume, tumour volume, extracapsular extension, seminal vesicle invasion, tumour extension into the apex or anterior to the urethra). Two factors were significant independent predictors of salvage HIFU failure: the PSA level at HIFU treatment (p < 0.012; risk ratio: 1.15, 95% CI: 1.03-1.29) and the tumour extension anterior to the urethra, as assessed by MRI (p = 0.046, risk ratio: 2.51, 95% CI: 1.02-6.16). The location of cancer recurrence anterior to the urethra on MRI is an independent significant predictor of salvage HIFU failure for locally recurrent prostate cancer after EBRT. Therefore, MRI may be useful for patient selection before post-EBRT salvage HIFU ablation. Copyright © 2013 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Leukocytosis and neutrophilia predict outcome in locally advanced esophageal cancer treated with definitive chemoradiation

PubMed Central

Schernberg, Antoine; Moureau-Zabotto, Laurence; Del Campo, Eleonor Rivin; Escande, Alexandre; Ducreux, Michel; Nguyen, France; Goere, Diane; Chargari, Cyrus; Deutsch, Eric

2017-01-01

Purpose To investigate the prognostic value of leukocyte and neutrophil count as biomarkers in patients with locally advanced esophageal squamous cell carcinoma (SCC) undergoing exclusive chemoradiation. Results A total of 126 patients were identified. Respectively, 33% and 35% displayed baseline leukocytosis and neutrophilia. Estimated 3-year OS and PFS from chemoradiation completion were 31% and 25%, respectively. In univariate analysis, both leukocytosis and neutrophilia were associated with worse OS, PFS, and LRC (p < 0.01). In multivariate analysis, leukocytosis remained an independent risk factor associated with poorer OS, PFS and LRC (p < 0.05), independently from tumor stage and length, with higher prognostic value for OS compared with patients’ performance status (PS). Materials and Methods Bi-institutional clinical records from consecutive non-operable patients treated between 2003 and 2015 with definitive chemoradiation for locally advanced esophageal carcinoma were reviewed. Leukocytosis and neutrophilia were defined as a leukocyte or neutrophil count over 10 G/L and 7 G/L, respectively. These parameters were studied for their potential correlation with overall survival (OS), progression free survival (PFS), locoregional control (LRC) and distant metastases control (DMC). Conclusions Leukocytosis and neutrophilia were independent prognostic factors of poor OS, PFS, and LRC in this bi-institutional series of locally advanced esophageal SCC treated with definitive chemoradiation. Although prospective confirmation is warranted, it is suggested that the leukocyte and neutrophil count parameters might be clinically relevant biomarkers to be considered for further clinical investigations. PMID:28086222

Assessing the scale of tumor heterogeneity by complete hierarchical segmentation of MRI.

PubMed

Gensheimer, Michael F; Hawkins, Douglas S; Ermoian, Ralph P; Trister, Andrew D

2015-02-07

In many cancers, intratumoral heterogeneity has been found in histology, genetic variation and vascular structure. We developed an algorithm to interrogate different scales of heterogeneity using clinical imaging. We hypothesize that heterogeneity of perfusion at coarse scale may correlate with treatment resistance and propensity for disease recurrence. The algorithm recursively segments the tumor image into increasingly smaller regions. Each dividing line is chosen so as to maximize signal intensity difference between the two regions. This process continues until the tumor has been divided into single voxels, resulting in segments at multiple scales. For each scale, heterogeneity is measured by comparing each segmented region to the adjacent region and calculating the difference in signal intensity histograms. Using digital phantom images, we showed that the algorithm is robust to image artifacts and various tumor shapes. We then measured the primary tumor scales of contrast enhancement heterogeneity in MRI of 18 rhabdomyosarcoma patients. Using Cox proportional hazards regression, we explored the influence of heterogeneity parameters on relapse-free survival. Coarser scale of maximum signal intensity heterogeneity was prognostic of shorter survival (p = 0.05). By contrast, two fractal parameters and three Haralick texture features were not prognostic. In summary, our algorithm produces a biologically motivated segmentation of tumor regions and reports the amount of heterogeneity at various distance scales. If validated on a larger dataset, this prognostic imaging biomarker could be useful to identify patients at higher risk for recurrence and candidates for alternative treatment.

MeSS: A novel prognostic scale specific for pediatric well-differentiated thyroid cancer: a population-based, SEER outcomes study.

PubMed

Shayota, Brian J; Pawar, Shonali C; Chamberlain, Ronald S

2013-09-01

High-risk prognostic factors for adults with well-differentiated thyroid cancer (WDTC) have been well established, but the same is not true for pediatric patients. This study sought to determine whether validated adult prognostic systems are applicable to pediatric patients and to develop a novel prognostic scale that may better reflect outcomes in pediatric subgroups. We queried 62,007 cases of WDTC from the Surveillance, Epidemiology, and End Results (SEER) database (1973-2009) to identify 895 patients <20 years of age with WDTC. Data abstracted included age, gender, race, histology type, primary tumor size, cancer stage, and mortality. Odds ratio and 95% confidence intervals were set and data were analyzed with SAS version 9.2. Among 895 pediatric WDTC patients, the overall cause-specific mortality was 0.8%. The presence of distant metastasis was associated with the worst prognosis (P = .0045) followed by larger primary tumor size (P = .0135) and male gender (P = .0162). When classified into low-, moderate-, and high-risk categories according to the distant metastasis (Me), larger primary tumor size (S), and male sex (S) (MeSS) algorithm, mortality rates were 0%, 2.7%, and 23%, respectively. Commonly used prognostic indices for WDTC in adults do not reliably predict poor outcomes among pediatric patients. Rather, a system based on MeSS is more applicable to pediatric patients. Patients who exhibit a high MeSS score have a significantly worse overall survival than those who do not express any MeSS characteristics. Copyright © 2013 Mosby, Inc. All rights reserved.

Intrahepatic cholangiocarcinoma prognostic determination using pre-operative serum C-reactive protein levels.

PubMed

Lin, Zi-Ying; Liang, Zhen-Xing; Zhuang, Pei-Lin; Chen, Jie-Wei; Cao, Yun; Yan, Li-Xu; Yun, Jing-Ping; Xie, Dan; Cai, Mu-Yan

2016-10-12

Serum C-reactive protein (CRP), an acute inflammatory response biomarker, has been recognized as an indicator of malignant disease progression. However, the prognostic significance of CRP levels collected before tumor removal in intrahepatic cholangiocarcinoma requires further investigation. We sampled the CRP levels in 140 patients with intrahepatic cholangiocarcinoma who underwent hepatectomies with regional lymphadenectomies between 2006 and 2013. A retrospective analysis of the clinicopathological data was performed. We focused on the impact of serum CRP on the patients' cancer-specific survival and recurrence-free survival rates. High levels of preoperative serum CRP were significantly associated with well-established clinicopathologic features, including gender, advanced tumor stage, and elevated carcinoembryonic antigen and carbohydrate antigen 19-9 levels (P < 0.05). Univariate analysis demonstrated a significant association between high levels of serum CRP and adverse cancer-specific survival (P = 0.001) and recurrence-free survival (P < 0.001). In patients with stage I/II intrahepatic cholangiocarcinoma, the serum CRP level was a prognostic indicator for cancer-specific survival. In patients with stage I/II or stage III/IV, the serum CRP level was a prognostic indicator for recurrence-free survival (P < 0.05). Additionally, multivariate analysis identified serum CRP level in intrahepatic cholangiocarcinoma as an independent prognostic factor (P < 0.05). We confirmed a significant association of elevated pre-operative CRP levels with poor clinical outcomes for the tested patients with intrahepatic cholangiocarcinoma. Our results indicate that the serum CRP level may represent a useful factor for patient stratification in intrahepatic cholangiocarcinoma management.

Geriatric nutritional risk index as a prognostic factor in patients with diffuse large B cell lymphoma.

PubMed

Kanemasa, Yusuke; Shimoyama, Tatsu; Sasaki, Yuki; Hishima, Tsunekazu; Omuro, Yasushi

2018-06-01

The geriatric nutritional risk index (GNRI) is a simple and well-established nutritional assessment tool that is a significant prognostic factor for various cancers. However, the role of the GNRI in predicting clinical outcomes of diffuse large B cell lymphoma (DLBCL) patients has not been investigated. To address this issue, we retrospectively analyzed a total of 476 patients with newly diagnosed de novo DLBCL. We defined the best cutoff value of the GNRI as 96.8 using a receiver operating characteristic curve. Patients with a GNRI < 96.8 had significantly lower overall survival (OS) and progression-free survival (PFS) than those with a GNRI ≥ 96.8 (5-year OS, 61.2 vs. 84.4%, P < 0.001; 5-year PFS, 53.7 vs. 75.8%, P < 0.001). Multivariate analysis showed that performance status, Ann Arbor stage, serum lactate dehydrogenase, and GNRI were independent prognostic factors for OS. Among patients with high-intermediate and high-risk by National Comprehensive Cancer Network-International Prognostic Index (NCCN-IPI), the 5-year OS was significantly lower in patients with a GNRI < 96.8 than in those with a GNRI ≥ 96.8 (high-intermediate risk, 59.5 vs. 75.2%, P = 0.006; high risk, 37.4 vs. 64.9%, P = 0.033). In the present study, we demonstrated that the GNRI was an independent prognostic factor in DLBCL patients. The GNRI could identify a population of poor-risk patients among those with high-intermediate and high-risk by NCCN-IPI.

Superior Prognostic Value of Cumulative Intracranial Tumor Volume Relative to Largest Intracranial Tumor Volume for Stereotactic Radiosurgery-Treated Brain Metastasis Patients.

PubMed

Hirshman, Brian R; Wilson, Bayard; Ali, Mir Amaan; Proudfoot, James A; Koiso, Takao; Nagano, Osamu; Carter, Bob S; Serizawa, Toru; Yamamoto, Masaaki; Chen, Clark C

2018-04-01

Two intracranial tumor volume variables have been shown to prognosticate survival of stereotactic-radiosurgery-treated brain metastasis patients: the largest intracranial tumor volume (LITV) and the cumulative intracranial tumor volume (CITV). To determine whether the prognostic value of the Scored Index for Radiosurgery (SIR) model can be improved by replacing one of its components-LITV-with CITV. We compared LITV and CITV in terms of their survival prognostication using a series of multivariable models that included known components of the SIR: age, Karnofsky Performance Score, status of extracranial disease, and the number of brain metastases. Models were compared using established statistical measures, including the net reclassification improvement (NRI > 0) and integrated discrimination improvement (IDI). The analysis was performed in 2 independent cohorts, each consisting of ∼3000 patients. In both cohorts, CITV was shown to be independently predictive of patient survival. Replacement of LITV with CITV in the SIR model improved the model's ability to predict 1-yr survival. In the first cohort, the CITV model showed an NRI > 0 improvement of 0.2574 (95% confidence interval [CI] 0.1890-0.3257) and IDI of 0.0088 (95% CI 0.0057-0.0119) relative to the LITV model. In the second cohort, the CITV model showed a NRI > 0 of 0.2604 (95% CI 0.1796-0.3411) and IDI of 0.0051 (95% CI 0.0029-0.0073) relative to the LITV model. After accounting for covariates within the SIR model, CITV offers superior prognostic value relative to LITV for stereotactic radiosurgery-treated brain metastasis patients.

Prognostic and predictive value of VHL gene alteration in renal cell carcinoma: a meta-analysis and review.

PubMed

Kim, Bum Jun; Kim, Jung Han; Kim, Hyeong Su; Zang, Dae Young

2017-02-21

The von Hippel-Lindau (VHL) gene is often inactivated in sporadic renal cell carcinoma (RCC) by mutation or promoter hypermethylation. The prognostic or predictive value of VHL gene alteration is not well established. We conducted this meta-analysis to evaluate the association between the VHL alteration and clinical outcomes in patients with RCC. We searched PUBMED, MEDLINE and EMBASE for articles including following terms in their titles, abstracts, or keywords: 'kidney or renal', 'carcinoma or cancer or neoplasm or malignancy', 'von Hippel-Lindau or VHL', 'alteration or mutation or methylation', and 'prognostic or predictive'. There were six studies fulfilling inclusion criteria and a total of 633 patients with clear cell RCC were included in the study: 244 patients who received anti-vascular endothelial growth factor (VEGF) therapy in the predictive value analysis and 419 in the prognostic value analysis. Out of 663 patients, 410 (61.8%) had VHL alteration. The meta-analysis showed no association between the VHL gene alteration and overall response rate (relative risk = 1.47 [95% CI, 0.81-2.67], P = 0.20) or progression free survival (hazard ratio = 1.02 [95% CI, 0.72-1.44], P = 0.91) in patients with RCC who received VEGF-targeted therapy. There was also no correlation between the VHL alteration and overall survival (HR = 0.80 [95% CI, 0.56-1.14], P = 0.21). In conclusion, this meta-analysis indicates that VHL gene alteration has no prognostic or predictive value in patients with clear cell RCC.

Prognostic and predictive value of VHL gene alteration in renal cell carcinoma: a meta-analysis and review

PubMed Central

Kim, Bum Jun; Kim, Jung Han; Kim, Hyeong Su; Zang, Dae Young

2017-01-01

The von Hippel-Lindau (VHL) gene is often inactivated in sporadic renal cell carcinoma (RCC) by mutation or promoter hypermethylation. The prognostic or predictive value of VHL gene alteration is not well established. We conducted this meta-analysis to evaluate the association between the VHL alteration and clinical outcomes in patients with RCC. We searched PUBMED, MEDLINE and EMBASE for articles including following terms in their titles, abstracts, or keywords: ‘kidney or renal’, ‘carcinoma or cancer or neoplasm or malignancy’, ‘von Hippel-Lindau or VHL’, ‘alteration or mutation or methylation’, and ‘prognostic or predictive’. There were six studies fulfilling inclusion criteria and a total of 633 patients with clear cell RCC were included in the study: 244 patients who received anti-vascular endothelial growth factor (VEGF) therapy in the predictive value analysis and 419 in the prognostic value analysis. Out of 663 patients, 410 (61.8%) had VHL alteration. The meta-analysis showed no association between the VHL gene alteration and overall response rate (relative risk = 1.47 [95% CI, 0.81-2.67], P = 0.20) or progression free survival (hazard ratio = 1.02 [95% CI, 0.72-1.44], P = 0.91) in patients with RCC who received VEGF-targeted therapy. There was also no correlation between the VHL alteration and overall survival (HR = 0.80 [95% CI, 0.56-1.14], P = 0.21). In conclusion, this meta-analysis indicates that VHL gene alteration has no prognostic or predictive value in patients with clear cell RCC. PMID:28103578

Density of tumor-infiltrating lymphocytes correlates with extent of brain edema and overall survival time in patients with brain metastases

PubMed Central

Berghoff, Anna S; Fuchs, Elisabeth; Ricken, Gerda; Mlecnik, Bernhard; Bindea, Gabriela; Spanberger, Thomas; Hackl, Monika; Widhalm, Georg; Dieckmann, Karin; Prayer, Daniela; Bilocq, Amelie; Heinzl, Harald; Zielinski, Christoph; Bartsch, Rupert; Birner, Peter; Galon, Jerome; Preusser, Matthias

2016-01-01

The immune microenvironment of the brain differs from that of other organs and the role of tumor-infiltrating lymphocytes (TILs) in brain metastases (BM), one of the most common and devastating complication of cancer, is unclear. We investigated TIL subsets and their prognostic impact in 116 BM specimens using immunohistochemistry for CD3, CD8, CD45RO, FOXP3, PD1 and PD-L1. The Immunoscore was calculated as published previously. Overall, we found TIL infiltration in 115/116 (99.1%) BM specimens. PD-L1 expression was evident in 19/67 (28.4%) BM specimens and showed no correlation with TIL density (p > 0.05). TIL density was not associated with corticosteroid administration (p > 0.05). A significant difference in infiltration density according to TIL subtype was present (p < 0.001; Chi Square); high infiltration was most frequently observed for CD3+ TILs (95/116; 81.9%) and least frequently for PD1+ TILs (18/116; 15.5%; p < 0.001). Highest TIL density was observed in melanoma, followed by renal cell cancer and lung cancer BM (p < 0.001). The density of CD8+ TILs correlated positively with the extent of peritumoral edema seen on pre-operative magnetic resonance imaging (p = 0.031). The density of CD3+ (15 vs. 6 mo; p = 0.015), CD8+ (15 vs. 11 mo; p = 0.030) and CD45RO+ TILs (18 vs. 8 mo; p = 0.006) showed a positive correlation with favorable median OS times. Immunoscore showed significant correlation with survival prognosis (27 vs. 10 mo; p < 0.001). The prognostic impact of Immunoscore was independent from established prognostic parameters at multivariable analysis (HR 0.612, p < 0.001). In conclusion, our data indicate that dense TILs infiltrates are common in BM and correlate with the amount of peritumoral brain edema and survival prognosis, thus identifying the immune system as potential biomarker for cancer patients with CNS affection. Further studies are needed to substantiate our findings. PMID:26942067

A combined pulmonary function and emphysema score prognostic index for staging in Chronic Obstructive Pulmonary Disease.

PubMed

Boutou, Afroditi K; Nair, Arjun; Douraghi-Zadeh, Dariush; Sandhu, Ranbir; Hansell, David M; Wells, Athol U; Polkey, Michael I; Hopkinson, Nicholas S

2014-01-01

Chronic Obstructive Pulmonary Disease (COPD) is characterized by high morbidity and mortality. Lung computed tomography parameters, individually or as part of a composite index, may provide more prognostic information than pulmonary function tests alone. To investigate the prognostic value of emphysema score and pulmonary artery measurements compared with lung function parameters in COPD and construct a prognostic index using a contingent staging approach. Predictors of mortality were assessed in COPD outpatients whose lung computed tomography, spirometry, lung volumes and gas transfer data were collected prospectively in a clinical database. Univariate and multivariate Cox proportional hazard analysis models with bootstrap techniques were used. 169 patients were included (59.8% male, 61.1 years old; Forced Expiratory Volume in 1 second % predicted: 40.5±19.2). 20.1% died; mean survival was 115.4 months. Age (HR = 1.098, 95% Cl = 1.04-1.252) and emphysema score (HR = 1.034, 95% CI = 1.007-1.07) were the only independent predictors of mortality. Pulmonary artery dimensions were not associated with survival. An emphysema score of 55% was chosen as the optimal threshold and 30% and 65% as suboptimals. Where emphysema score was between 30% and 65% (intermediate risk) the optimal lung volume threshold, a functional residual capacity of 210% predicted, was applied. This contingent staging approach separated patients with an intermediate risk based on emphysema score alone into high risk (Functional Residual Capacity ≥210% predicted) or low risk (Functional Residual Capacity <210% predicted). This approach was more discriminatory for survival (HR = 3.123; 95% CI = 1.094-10.412) than either individual component alone. Although to an extent limited by the small sample size, this preliminary study indicates that the composite Emphysema score-Functional Residual Capacity index might provide a better separation of high and low risk patients with COPD, than other individual predictors alone.

[Novel Scale for Long-Term Prognostication of Risk of Death and Nonfatal Cardiovascular Complications in Patients From the PROGNOSIS-IHD Registry].

PubMed

Tolpygina, S N; Martsevich, S Yu; Gofman, E A; Deev, A D

2016-06-01

To elaborate a risk score for prognostication of long-term survival of patients with chronic ischemic heart disease (CIHD) using data of the PROGNOSIS-IHD Registry. Participants of the PROGNOSIS-IHD Registry (n=641, 500 men, 141 women) were inhabitants of Moscow region consecutively admitted for planned hospitalization with diagnosis of IHD to the clinic of the Center of Preventive Medicine from 01.01.2004 to 31.12.2007. During hospitalization all patients underwent coronary angiography. Diagnosis of IHD was not confirmed in 100 of 641 patients. In 2010 vital status was determined in 551 patients (86%). Mean duration of observation was 3.9 years. Uni- and multi-factorial analysis was used for assessment of prognostic value of clinical-anamnestic and instrumental parameters. The following parameters which were included into the risk score were most significant for prediction of occurrence of a primary end point (fatal and nonfatal cardiovascular complications [CVC]): feeling of shortness of breath (relative risk [RR] 1.86 and 1 point in risk score); history of unstable IHD course (acute coronary syndrome, myocardial infarction, unstable angina) (RR 1.76 and 1 point); need in diuretics before hospitalization (RR 1.92 and 1 point); stenosis of a cardiac valve (RR 2.95 and 2 points); zones of abnormal contractility of left ventricular myocardium at echocardiography (RR 2 and 1 point). Risk of death and nonfatal CVC in patients with suspected IHD was considered very low, low, medium, and high at score values 0, 1 (RR 1.6), 2 (RR 2.4), and more or equal 3 (RR 6.1), respectively. Novel scale has high prognostic significance relative to stratification of risk of death and nonfatal CVC in patients with suspected CIHD and can be used in wide clinical practice because of its informativeness, simplicity, and accessibility.

Detrended Fluctuation Analysis of Heart Rate Dynamics Is an Important Prognostic Factor in Patients with End-Stage Renal Disease Receiving Peritoneal Dialysis

PubMed Central

Lin, Lian-Yu; Chang, Chin-Hao; Chu, Fang-Ying; Lin, Yen-Hung; Wu, Cho-Kai; Lee, Jen-Kuang; Hwang, Juei-Jen; Lin, Jiunn-Lee; Chiang, Fu-Tien

2016-01-01

Background and Objectives Patients with severe kidney function impairment often have autonomic dysfunction, which could be evaluated noninvasively by heart rate variability (HRV) analysis. Nonlinear HRV parameters such as detrended fluctuation analysis (DFA) has been demonstrated to be an important outcome predictor in patients with cardiovascular diseases. Whether cardiac autonomic dysfunction measured by DFA is also a useful prognostic factor in patients with end-stage renal disease (ESRD) receiving peritoneal dialysis (PD) remains unclear. The purpose of the present study was designed to test the hypothesis. Materials and Methods Patients with ESRD receiving PD were included for the study. Twenty-four hour Holter monitor was obtained from each patient together with other important traditional prognostic makers such as underlying diseases, left ventricular ejection fraction (LVEF) and serum biochemistry profiles. Short-term (DFAα1) and long-term (DFAα2) DFA as well as other linear HRV parameters were calculated. Results A total of 132 patients (62 men, 72 women) with a mean age of 53.7±12.5 years were recruited from July 2007 to March 2009. During a median follow-up period of around 34 months, eight cardiac and six non-cardiac deaths were observed. Competing risk analysis demonstrated that decreased DFAα1 was a strong prognostic predictor for increased cardiac and total mortality. ROC analysis showed that the AUC of DFAα1 (<0.95) to predict mortality was 0.761 (95% confidence interval (CI). = 0.617–0.905). DFAα1≧ 0.95 was associated with lower cardiac mortality (Hazard ratio (HR) 0.062, 95% CI = 0.007–0.571, P = 0.014) and total mortality (HR = 0.109, 95% CI = 0.033–0.362, P = 0.0003). Conclusion Cardiac autonomic dysfunction evaluated by DFAα1 is an independent predictor for cardiac and total mortality in patients with ESRD receiving PD. PMID:26828209

Prognostic significance of myocardial energy expenditure and myocardial efficiency in patients with heart failure with reduced ejection fraction.

PubMed

Cetin, Mehmet S; Ozcan Cetin, Elif H; Canpolat, Ugur; Sasmaz, Hatice; Temizhan, Ahmet; Aydogdu, Sinan

2018-02-01

In heart failure with reduced ejection fraction (HFrEF) patients, myocardial blood flow (MBF), myocardial energy expenditure (MEE), myocardial efficiency has been poorly evaluated because of the necessity of invasive procedures in the determination of these parameters. Transthoracic echocardiography (TTE) can provide reliable data for MEE, MBF (via coronary sinus (CS) flows). Also, myocardial efficiency can be evaluated by the MEE to MBF ratio. We aim to assess MBF, MEE and energy efficiency and the prognostic value of these parameters in HFrEF. In this prospective study, a total of 80 patients with HFrEF due to either ischemic or non-ischemic etiology and 20 healthy control subjects were included. Median follow-up duration was 901 (27-1004) days. MBF was calculated via coronary sinus blood flow. MEE was measured from circumferential end-systolic stress, stroke volume and left ventricular ejection time. MEE to MBF ratio was determined as MEf. Primary composite end-point (CEP) was cardiovascular mortality, heart transplantation or mechanical circulatory support. MEE and MEf were lower and MBF per minute was higher in HF group compared to control subjects whereas MBF per 100 g left ventricular mass was not different. MEE and MEf have significantly negative correlation with troponin I, BNP, uric acid and positive correlation with epicardial fat thickness. In Cox regression analysis, per one calorie decrease of MEE was associated 4.3 times increased risk [HR 4.396 (95% CI 1.230-15.716)] and per one percent decrease of MEf was associated 3.3 times increased risk of CEP [HR 3.343 (95% CI 1.025-10.905)]. Our study demonstrated that while MEE and MEf diminished in HFrEF, MBF preserved with the symptomatic progression of HF. MEE and MEf were found to be associated with important prognostic markers and independent predictors of CEP in HFrEF. Evaluation of MEE, MBF and MEf with echocardiography may provide an additional data regarding prognostic assessment of HFrEF population.

Value of Excess Pressure Integral for Predicting 15-Year All-Cause and Cardiovascular Mortalities in End-Stage Renal Disease Patients.

PubMed

Huang, Jui-Tzu; Cheng, Hao-Min; Yu, Wen-Chung; Lin, Yao-Ping; Sung, Shih-Hsien; Wang, Jiun-Jr; Wu, Chung-Li; Chen, Chen-Huan

2017-11-29

The excess pressure integral (XSPI), derived from analysis of the arterial pressure curve, may be a significant predictor of cardiovascular events in high-risk patients. We comprehensively investigated the prognostic value of XSPI for predicting long-term mortality in end-stage renal disease patients undergoing regular hemodialysis. A total of 267 uremic patients (50.2% female; mean age 54.2±14.9 years) receiving regular hemodialysis for more than 6 months were enrolled. Cardiovascular parameters were obtained by echocardiography and applanation tonometry. Calibrated carotid arterial pressure waveforms were analyzed according to the wave-transmission and reservoir-wave theories. Multivariable Cox proportional hazard models were constructed to account for age, sex, diabetes mellitus, albumin, body mass index, and hemodialysis treatment adequacy. Incremental utility of the parameters to risk stratification was assessed by net reclassification improvement. During a median follow-up of 15.3 years, 124 deaths (46.4%) incurred. Baseline XSPI was significantly predictive of all-cause (hazard ratio per 1 SD 1.4, 95% confidence interval 1.15-1.70, P =0.0006) and cardiovascular mortalities (1.47, 1.18-1.84, P =0.0006) after accounting for the covariates. The addition of XSPI to the base prognostic model significantly improved prediction of both all-cause mortality (net reclassification improvement=0.1549, P =0.0012) and cardiovascular mortality (net reclassification improvement=0.1535, P =0.0033). XSPI was superior to carotid-pulse wave velocity, forward and backward wave amplitudes, and left ventricular ejection fraction in consideration of overall independent and incremental prognostics values. In end-stage renal disease patients undergoing regular hemodialysis, XSPI was significantly predictive of long-term mortality and demonstrated an incremental value to conventional prognostic factors. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Osteopontin: A non-invasive parameter of portal hypertension and prognostic marker of cirrhosis.

PubMed

Bruha, Radan; Jachymova, Marie; Petrtyl, Jaromir; Dvorak, Karel; Lenicek, Martin; Urbanek, Petr; Svestka, Tomislav; Vitek, Libor

2016-03-28

To investigate the relationship between osteopontin plasma concentrations and the severity of portal hypertension and to assess osteopontin prognostic value. A cohort of 154 patients with confirmed liver cirrhosis (112 ethylic, 108 men, age 34-72 years) were enrolled in the study. Hepatic venous pressure gradient (HVPG) measurement and laboratory and ultrasound examinations were carried out for all patients. HVPG was measured using a standard catheterization method with the balloon wedge technique. Osteopontin was measured using the enzyme-linked immunosorbent assay (ELISA) method in plasma. Patients were followed up with a specific focus on mortality. The control group consisted of 137 healthy age- and sex- matched individuals. The mean value of HVPG was 16.18 ± 5.6 mmHg. Compared to controls, the plasma levels of osteopontin in cirrhotic patients were significantly higher (P < 0.001). The plasma levels of osteopontin were positively related to HVPG (P = 0.0022, r = 0.25) and differed among the individual Child-Pugh groups of patients. The cut-off value of 80 ng/mL osteopontin distinguished patients with significant portal hypertension (HVPG above 10 mmHg) at 75% sensitivity and 63% specificity. The mean follow-up of patients was 3.7 ± 2.6 years. The probability of cumulative survival was 39% for patients with HVPG > 10 mmHg and 65% for those with HVPG ≤ 10 mmHg (P = 0.0086, odds ratio (OR), 2.92, 95% confidence interval (CI): 1.09-7.76). Osteopontin showed a similar prognostic value to HVPG. Patients with osteopontin values above 80 ng/mL had significantly lower cumulative survival compared to those with osteopontin ≤ 80 ng/mL (37% vs 56%, P = 0.00035; OR = 2.23, 95%CI: 1.06-4.68). Osteopontin is a non-invasive parameter of portal hypertension that distinguishes patients with clinically significant portal hypertension. It is a strong prognostic factor for survival.

Prognostic Utility of Cell Cycle Progression Score in Men With Prostate Cancer After Primary External Beam Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Freedland, Stephen J., E-mail: steve.freedland@duke.edu; Department of Surgery; Department of Pathology, Duke University School of Medicine, Durham, North Carolina

Purpose: To evaluate the prognostic utility of the cell cycle progression (CCP) score, a RNA signature based on the average expression level of 31 CCP genes, for predicting biochemical recurrence (BCR) in men with prostate cancer treated with external beam radiation therapy (EBRT) as their primary curative therapy. Methods and Materials: The CCP score was derived retrospectively from diagnostic biopsy specimens of men diagnosed with prostate cancer from 1991 to 2006 (n=141). All patients were treated with definitive EBRT; approximately half of the cohort was African American. Outcome was time from EBRT to BCR using the Phoenix definition. Median follow-upmore » for patients without BCR was 4.8 years. Association with outcome was evaluated by Cox proportional hazards survival analysis and likelihood ratio tests. Results: Of 141 patients, 19 (13%) had BCR. The median CCP score for patient samples was 0.12. In univariable analysis, CCP score significantly predicted BCR (P=.0017). The hazard ratio for BCR was 2.55 for 1-unit increase in CCP score (equivalent to a doubling of gene expression). In a multivariable analysis that included Gleason score, prostate-specific antigen, percent positive cores, and androgen deprivation therapy, the hazard ratio for CCP changed only marginally and remained significant (P=.034), indicating that CCP provides prognostic information that is not provided by standard clinical parameters. With 10-year censoring, the CCP score was associated with prostate cancer-specific mortality (P=.013). There was no evidence for interaction between CCP and any clinical variable, including ethnicity. Conclusions: Among men treated with EBRT, the CCP score significantly predicted outcome and provided greater prognostic information than was available with clinical parameters. If validated in a larger cohort, CCP score could identify high-risk men undergoing EBRT who may need more aggressive therapy.« less

Scholastic Achievement of Higher Secondary Students in Science Stream

ERIC Educational Resources Information Center

Khan, Zebun Nisa

2005-01-01

The present study was conducted on 400 students (200 Boys and 200 Girls) selected from Senior Secondary School of A. M. U. Aligarh; India to establish the prognostic value of different measures of cognition, personality and demographic variables for success at Higher Secondary level in Science stream. The score obtained on different variables are…

Impaired Gas Exchange: Prognostic Clinical Indicators of Short-Term Survival in Children with Acute Respiratory Infection.

PubMed

Pascoal, Lívia Maia; de Oliveira Lopes, Marcos Venícios; Chaves, Daniel Bruno Resende; Beltrão, Beatriz Amorim; Nunes, Marília Mendes; da Silva, Viviane Martins; de Sousa Freire, Vanessa Emille Carvalho

2018-02-10

To establish prognostic indicators of survival for impaired gas exchange (IGE) (00030). Secondary analysis of data from an open prospective cohort developed with a group of 136 children with acute respiratory infection (ARI). On Day 1, IGE (00030) was present in 42.6% of the sample. New cases arose until the last day of evaluation. With regards to defining characteristics, only hypoxemia and abnormal skin color were associated with a higher risk of developing diagnosis. Children with ARI who exhibit hypoxemia and abnormal skin color had a worse prognosis for IGE (00030). Nurses can use the research findings as a predictive marker of the evolution of the patient's health status. © 2018 NANDA International, Inc.

Chronic lymphocytic leukemia: A prognostic model comprising only two biomarkers (IGHV mutational status and FISH cytogenetics) separates patients with different outcome and simplifies the CLL-IPI.

PubMed

Delgado, Julio; Doubek, Michael; Baumann, Tycho; Kotaskova, Jana; Molica, Stefano; Mozas, Pablo; Rivas-Delgado, Alfredo; Morabito, Fortunato; Pospisilova, Sarka; Montserrat, Emili

2017-04-01

Rai and Binet staging systems are important to predict the outcome of patients with chronic lymphocytic leukemia (CLL) but do not reflect the biologic diversity of the disease nor predict response to therapy, which ultimately shape patients' outcome. We devised a biomarkers-only CLL prognostic system based on the two most important prognostic parameters in CLL (i.e., IGHV mutational status and fluorescence in situ hybridization [FISH] cytogenetics), separating three different risk groups: (1) low-risk (mutated IGHV + no adverse FISH cytogenetics [del(17p), del(11q)]); (2) intermediate-risk (either unmutated IGHV or adverse FISH cytogenetics) and (3) high-risk (unmutated IGHV + adverse FISH cytogenetics). In 524 unselected subjects with CLL, the 10-year overall survival was 82% (95% CI 76%-88%), 52% (45%-62%), and 27% (17%-42%) for the low-, intermediate-, and high-risk groups, respectively. Patients with low-risk comprised around 50% of the series and had a life expectancy comparable to the general population. The prognostic model was fully validated in two independent cohorts, including 417 patients representative of general CLL population and 337 patients with Binet stage A CLL. The model had a similar discriminatory value as the CLL-IPI. Moreover, it applied to all patients with CLL independently of age, and separated patients with different risk within Rai or Binet clinical stages. The biomarkers-only CLL prognostic system presented here simplifies the CLL-IPI and could be useful in daily practice and to stratify patients in clinical trials. © 2017 Wiley Periodicals, Inc.

Prognostic value of calcium score and coronary flow velocity reserve in asymptomatic diabetic patients.

PubMed

Dikic, Miodrag; Tesic, Milorad; Markovic, Zeljko; Giga, Vojislav; Djordjevic-Dikic, Ana; Stepanovic, Jelena; Beleslin, Branko; Jovanovic, Ivana; Mladenovic, Ana; Seferovic, Jelena; Ostojic, Miodrag; Arandjelovic, Aleksandra

2015-09-04

The risk stratification of patients with diabetes mellitus (DM) is a major objective for the clinicians, and it can be achieved by coronary flow velocity reserve (CFVR) or with coronary artery calcium score (CS). CS evaluates underlying coronary atherosclerotic plaque burden and CFVR estimates both presence of coronary artery stenosis and microvascular function. Consequently, CFVR may provide unique risk information beyond the extent of coronary atherosclerosis. Our aim is to assess joint prognostic value of CFVR and CS in asymptomatic DM patients. We prospectively included 200 asymptomatic patients (45,5 % male, mean age 57,35 ± 11,25), out of which, there were 101 asymptomatic patients with DM and 99 asymptomatic patients without DM, but with one or more conventionally risk factors for coronary artery disease. We analyzed clinical, biochemical, metabolic, inflammatory parameters, CS by Agatston method, transthoracic Doppler echocardiography CFVR of left anterior descending artery and echocardiographic parameters. Total CS and CS LAD were significantly higher, while mean CFVR was lower in diabetics compared to the nondiabetics. During 1 year follow-up, 24 patients experienced cardio-vascular events (one cardiovascular death, two strokes, three myocardial infarctions, nine new onsets of unstable angina and nine myocardial revascularizations): 19 patients with DM and five non DM patients, (p = 0,003). Overall event free survival was significantly higher in non DM group, compared to the DM group (94,9 % vs. 81,2 %, p = 0,002 respectively), while the patients with CS ≥200 and CFVR <2 had the worst outcome during 1 year follow up in the whole study population as well as in the DM group. At multivariable analysis CFVR on LAD (HR 12.918, 95 % CI 3.865-43.177, p < 0.001) and total CS (HR 13.393, 95 % CI 1.675-107.119, p = 0.014) were independent prognostic predictors of adverse events in DM group of patients. Both CS and CFVR provide independent and complementary prognostic information in asymptomatic DM patients. When two parameters are analyzed together, the risk stratification ability improves, even when DM patients are analyzed together with non DM patients. As a result, DM patients with CS ≥200 and CFVR <2 had the worst outcome. Consequently, the use of two tests identified subset of patients who can derive the most benefit from the intensive prevention measures.

Does weather affect daily pain intensity levels in patients with acute low back pain? A prospective cohort study.

PubMed

Duong, Vicky; Maher, Chris G; Steffens, Daniel; Li, Qiang; Hancock, Mark J

2016-05-01

The aim of this study was to investigate the influence of various weather parameters on pain intensity levels in patients with acute low back pain (LBP). We performed a secondary analysis using data from the PACE trial that evaluated paracetamol (acetaminophen) in the treatment of acute LBP. Data on 1604 patients with LBP were included in the analysis. Weather parameters (precipitation, temperature, relative humidity, and air pressure) were obtained from the Australian Bureau of Meteorology. Pain intensity was assessed daily on a 0-10 numerical pain rating scale over a 2-week period. A generalised estimating equation analysis was used to examine the relationship between daily pain intensity levels and weather in three different time epochs (current day, previous day, and change between previous and current days). A second model was adjusted for important back pain prognostic factors. The analysis did not show any association between weather and pain intensity levels in patients with acute LBP in each of the time epochs. There was no change in strength of association after the model was adjusted for prognostic factors. Contrary to common belief, the results demonstrated that the weather parameters of precipitation, temperature, relative humidity, and air pressure did not influence the intensity of pain reported by patients during an episode of acute LBP.

Criteria predictive of limb viability at 1 year in patients with chronic severe ischemia--TcPO2 and demographic parameters.

PubMed

Chomard, D; Habault, P; Eveno, D; Le Lamer, S; Ledemeney, M; Haon, C

2000-09-01

Following an earlier study, the investigators sought to identify and define objective prognostic criteria of viability at 1 year of a limb with severe chronic ischemia. A study was undertaken in 116 patients (118 limbs) (74 men and 42 women), with a mean age of 71.9 years for men and 81.6 years for women. Static transcutaneous oxygen pressure (TcPO2) was measured with a verticalization sensitization test and inhalation of oxygen on JO and viability of the limb noted 1 year later. Logistic analysis was made of 13 oximetry parameters and two demographic parameters (age and gender). Results were analyzed in absolute terms and by tissue oxygenation ratio (TOR) (ratio between absolute TcPO2 at the foot and at a chest reference electrode). Six factors appeared to be prognostic factors of limb viability at 1 year, statistically significant at 6% according to threshold values: age, verticalization TcPO2, TcPO2 after 1 minute's inhalation of oxygen, TcPO2 after 4 minutes' inhalation of oxygen, and slope of TcPO2 and slope of TOR between 1 and 4 minutes' inhalation. A 1 year viability index integrating these criteria is suggested.

CRC-113 gene expression signature for predicting prognosis in patients with colorectal cancer

PubMed Central

Nguyen, Dinh Truong; Kim, Jin-Hwan; Jo, Yong Hwa; Shahid, Muhammad; Akter, Salima; Aryal, Saurav Nath; Yoo, Ji Youn; Ahn, Yong-Joo; Cho, Kyoung Min; Lee, Ju-Seog; Choe, Wonchae; Kang, Insug; Ha, Joohun; Kim, Sung Soo

2015-01-01

Colorectal cancer (CRC) is the third leading cause of global cancer mortality. Recent studies have proposed several gene signatures to predict CRC prognosis, but none of those have proven reliable for predicting prognosis in clinical practice yet due to poor reproducibility and molecular heterogeneity. Here, we have established a prognostic signature of 113 probe sets (CRC-113) that include potential biomarkers and reflect the biological and clinical characteristics. Robustness and accuracy were significantly validated in external data sets from 19 centers in five countries. In multivariate analysis, CRC-113 gene signature showed a stronger prognostic value for survival and disease recurrence in CRC patients than current clinicopathological risk factors and molecular alterations. We also demonstrated that the CRC-113 gene signature reflected both genetic and epigenetic molecular heterogeneity in CRC patients. Furthermore, incorporation of the CRC-113 gene signature into a clinical context and molecular markers further refined the selection of the CRC patients who might benefit from postoperative chemotherapy. Conclusively, CRC-113 gene signature provides new possibilities for improving prognostic models and personalized therapeutic strategies. PMID:26397224

CRC-113 gene expression signature for predicting prognosis in patients with colorectal cancer.

PubMed

Nguyen, Minh Nam; Choi, Tae Gyu; Nguyen, Dinh Truong; Kim, Jin-Hwan; Jo, Yong Hwa; Shahid, Muhammad; Akter, Salima; Aryal, Saurav Nath; Yoo, Ji Youn; Ahn, Yong-Joo; Cho, Kyoung Min; Lee, Ju-Seog; Choe, Wonchae; Kang, Insug; Ha, Joohun; Kim, Sung Soo

2015-10-13

Colorectal cancer (CRC) is the third leading cause of global cancer mortality. Recent studies have proposed several gene signatures to predict CRC prognosis, but none of those have proven reliable for predicting prognosis in clinical practice yet due to poor reproducibility and molecular heterogeneity. Here, we have established a prognostic signature of 113 probe sets (CRC-113) that include potential biomarkers and reflect the biological and clinical characteristics. Robustness and accuracy were significantly validated in external data sets from 19 centers in five countries. In multivariate analysis, CRC-113 gene signature showed a stronger prognostic value for survival and disease recurrence in CRC patients than current clinicopathological risk factors and molecular alterations. We also demonstrated that the CRC-113 gene signature reflected both genetic and epigenetic molecular heterogeneity in CRC patients. Furthermore, incorporation of the CRC-113 gene signature into a clinical context and molecular markers further refined the selection of the CRC patients who might benefit from postoperative chemotherapy. Conclusively, CRC-113 gene signature provides new possibilities for improving prognostic models and personalized therapeutic strategies.

Construction of robust prognostic predictors by using projective adaptive resonance theory as a gene filtering method.

PubMed

Takahashi, Hiro; Kobayashi, Takeshi; Honda, Hiroyuki

2005-01-15

For establishing prognostic predictors of various diseases using DNA microarray analysis technology, it is desired to find selectively significant genes for constructing the prognostic model and it is also necessary to eliminate non-specific genes or genes with error before constructing the model. We applied projective adaptive resonance theory (PART) to gene screening for DNA microarray data. Genes selected by PART were subjected to our FNN-SWEEP modeling method for the construction of a cancer class prediction model. The model performance was evaluated through comparison with a conventional screening signal-to-noise (S2N) method or nearest shrunken centroids (NSC) method. The FNN-SWEEP predictor with PART screening could discriminate classes of acute leukemia in blinded data with 97.1% accuracy and classes of lung cancer with 90.0% accuracy, while the predictor with S2N was only 85.3 and 70.0% or the predictor with NSC was 88.2 and 90.0%, respectively. The results have proven that PART was superior for gene screening. The software is available upon request from the authors. honda@nubio.nagoya-u.ac.jp

Vehicle Integrated Prognostic Reasoner (VIPR) 2010 Annual Final Report

NASA Technical Reports Server (NTRS)

Hadden, George D.; Mylaraswamy, Dinkar; Schimmel, Craig; Biswas, Gautam; Koutsoukos, Xenofon; Mack, Daniel

2011-01-01

Honeywell's Central Maintenance Computer Function (CMCF) and Aircraft Condition Monitoring Function (ACMF) represent the state-of-the art in integrated vehicle health management (IVHM). Underlying these technologies is a fault propagation modeling system that provides nose-to-tail coverage and root cause diagnostics. The Vehicle Integrated Prognostic Reasoner (VIPR) extends this technology to interpret evidence generated by advanced diagnostic and prognostic monitors provided by component suppliers to detect, isolate, and predict adverse events that affect flight safety. This report describes year one work that included defining the architecture and communication protocols and establishing the user requirements for such a system. Based on these and a set of ConOps scenarios, we designed and implemented a demonstration of communication pathways and associated three-tiered health management architecture. A series of scripted scenarios showed how VIPR would detect adverse events before they escalate as safety incidents through a combination of advanced reasoning and additional aircraft data collected from an aircraft condition monitoring system. Demonstrating VIPR capability for cases recorded in the ASIAS database and cross linking them with historical aircraft data is planned for year two.

NADiA ProsVue prostate-specific antigen slope is an independent prognostic marker for identifying men at reduced risk of clinical recurrence of prostate cancer after radical prostatectomy.

PubMed

Moul, Judd W; Lilja, Hans; Semmes, O John; Lance, Raymond S; Vessella, Robert L; Fleisher, Martin; Mazzola, Clarisse; Sarno, Mark J; Stevens, Barbara; Klem, Robert E; McDermed, Jonathan E; Triebell, Melissa T; Adams, Thomas H

2012-12-01

To validate the hypothesis that men displaying serum prostate-specific antigen (PSA) slopes ≤ 2.0 pg/mL/mo after prostatectomy, measured using a new immuno-polymerase chain reaction diagnostic test (NADiA ProsVue), have a reduced risk of clinical recurrence as determined by positive biopsy, imaging findings, or death from prostate cancer. From 4 clinical sites, we selected a cohort of 304 men who had been followed up for 17.6 years after prostatectomy for clinical recurrence. We assessed the prognostic value of a PSA slope cutpoint of 2.0 pg/mL/mo against established risk factors to identify men at low risk of clinical recurrence using uni- and multivariate Cox proportional hazards regression and Kaplan-Meier analyses. The univariate hazard ratio of a PSA slope >2.0 pg/mL/mo was 18.3 (95% confidence interval 10.6-31.8) compared with a slope ≤ 2.0 pg/mL/mo (P <.0001). The median disease-free survival interval was 4.8 years vs >10 years in the 2 groups (P <.0001). The multivariate hazard ratio for PSA slope with the covariates of preprostatectomy PSA, pathologic stage, and Gleason score was 9.8 (95% confidence interval 5.4-17.8), an 89.8% risk reduction for men with PSA slopes ≤ 2.0 pg/mL/mo (P <.0001). The Gleason score (<7 vs ≥ 7) was the only other significant predictor (hazard ratio 5.4, 95% confidence interval 2.1-13.8, P = .0004). Clinical recurrence after radical prostatectomy is difficult to predict using established risk factors. We have demonstrated that a NADiA ProsVue PSA slope of ≤ 2.0 pg/mL/mo after prostatectomy is prognostic for a reduced risk of prostate cancer recurrence and adds predictive power to the established risk factors. Copyright © 2012 Elsevier Inc. All rights reserved.

NADiA® ProsVue™ PSA Slope Is an Independent Prognostic Marker for Identifying Men at Reduced Risk for Clinical Recurrence of Prostate Cancer after Radical Prostatectomy

PubMed Central

Moul, Judd W.; Lilja, Hans; Semmes, O. John; Lance, Raymond S.; Vessella, Robert L.; Fleisher, Martin; Mazzola, Clarisse; Sarno, Mark J.; Stevens, Barbara; Klem, Robert E.; McDermed, Jonathan E.; Triebell, Melissa T.; Adams, Thomas H.

2015-01-01

Objectives To validate the hypothesis that men displaying serum PSA slopes ≤2.0 pg/mL/month postprostatectomy, measured with a new immuno-PCR diagnostic test (NADiA® ProsVue™) were at a reduced risk of clinical recurrence as determined by positive biopsy, imaging or death due to prostate cancer. Methods From 4 clinical sites, we selected a cohort of 304 men followed up to 17.6 years postprostatectomy for clinical recurrence. We assessed the prognostic value of a PSA slope cutpoint of 2.0 pg/mL/month against established risk factors to identify men at very low risk of clinical recurrence using uni- and multivariate Cox proportional hazards regression and Kaplan-Meier analysis. Results The univariate HR (95% CI) of a PSA slope >2.0 pg/mL/month was 18.3 (10.6–31.8), compared to a slope ≤2.0 pg/mL/month (P <0.0001). Median disease-free survival was 4.8 years versus >10 years in the 2 groups (P <0.0001). Multivariate HR for PSA slope with the covariates of preprostatectomy PSA, pathologic stage and Gleason score was 9.8 (5.4–17.8), an 89.8% risk reduction, for men with PSA slopes ≤2.0 pg/mL/month (P <0.0001). Gleason Score (<7 vs. ≥7) was the only other significant predictor (HR 5.4, 2.1–13.8, P = 0.0004). Conclusions Clinical recurrence following radical prostatectomy is often difficult to predict since established factors do not reliably stratify risk. We demonstrate that a NADiA ProsVue slope ≤2.0 pg/mL/month postprostatectomy is prognostic for reduced risk of prostate cancer recurrence and adds predictive power to established risk factors. PMID:23107099

Comparison of Prognostic and Diagnostic Approaches to Modeling Evapotranspiration in the Nile River Basin

NASA Astrophysics Data System (ADS)

Yilmaz, M.; Anderson, M. C.; Zaitchik, B. F.; Crow, W. T.; Hain, C.; Ozdogan, M.; Chun, J. A.

2012-12-01

Actual evapotranspiration (ET) can be estimated using both prognostic and diagnostic modeling approaches, providing independent yet complementary information for hydrologic applications. Both approaches have advantages and disadvantages. When provided with temporally continuous atmospheric forcing data, prognostic models offer continuous sub-daily ET information together with the full set of water and energy balance fluxes and states (i.e. soil moisture, runoff, sensible and latent heat). On the other hand, the diagnostic modeling approach provides ET estimates over regions where reliable information about available soil water is not known (e.g., due to irrigation practices or shallow ground water levels not included in the prognostic model structure, unknown soil texture or plant rooting depth, etc). Prognostic model-based ET estimates are of great interest whenever consistent and complete water budget information is required or when there is a need to project ET for climate or land use change scenarios. Diagnostic models establish a stronger link to remote sensing observations, can be applied in regions with limited or questionable atmospheric forcing data, and provide valuable observation-derived information about the current land-surface state. Analysis of independently obtained ET estimates is particularly important in data poor regions. Such comparisons can help to reduce the uncertainty in the modeled ET estimates and to exclude outliers based on physical considerations. The Nile river basin is home to tens of millions of people whose daily life depends on water extracted from the river Nile. Yet the complete basin scale water balance of the Nile has been studied only a few times, and the temporal and the spatial distribution of hydrological fluxes (particularly ET) are still a subject of active research. This is due in part to a scarcity of ground-based station data for validation. In such regions, comparison between prognostic and diagnostic model output may be a valuable model evaluation tool. Motivated by the complementary information that exists in prognostic and diagnostic energy balance modeling, as well as the need for evaluation of water consumption estimates over the Nile basin, the purpose of this study is to 1) better describe the conceptual differences between prognostic and diagnostic modeling, 2) present the potential for diagnostic models to capture important hydrologic features that are not explicitly represented in prognostic model, 3) explore the differences in these two approaches over the Nile Basin, where ground data are sparse and transnational data sharing is unreliable. More specifically, we will compare output from the Noah prognostic model and the Atmosphere-Land Exchange Inverse (ALEXI) diagnostic model generated over ground truth data-poor Nile basin. Preliminary results indicate spatially, temporally, and magnitude wise consistent flux estimates for ALEXI and NOAH over irrigated Delta region, while there are differences over river-fed wetlands.

The long non-coding RNA HOTAIR is transcriptionally activated by HOXA9 and is an independent prognostic marker in patients with malignant glioma

PubMed Central

Xavier-Magalhães, Ana; Gonçalves, Céline S.; Fogli, Anne; Lourenço, Tatiana; Pojo, Marta; Pereira, Bruno; Rocha, Miguel; Lopes, Maria Celeste; Crespo, Inês; Rebelo, Olinda; Tão, Herminio; Lima, João; Moreira, Ricardo; Pinto, Afonso A.; Jones, Chris; Reis, Rui M.; Costello, Joseph F.; Arnaud, Philippe; Sousa, Nuno; Costa, Bruno M.

2018-01-01

The lncRNA HOTAIR has been implicated in several human cancers. Here, we evaluated the molecular alterations and upstream regulatory mechanisms of HOTAIR in glioma, the most common primary brain tumors, and its clinical relevance. HOTAIR gene expression, methylation, copy-number and prognostic value were investigated in human gliomas integrating data from online datasets and our cohorts. High levels of HOTAIR were associated with higher grades of glioma, particularly IDH wild-type cases. Mechanistically, HOTAIR was overexpressed in a gene dosage-independent manner, while DNA methylation levels of particular CpGs in HOTAIR locus were associated with HOTAIR expression levels in GBM clinical specimens and cell lines. Concordantly, the demethylating agent 5-Aza-2′-deoxycytidine affected HOTAIR transcriptional levels in a cell line-dependent manner. Importantly, HOTAIR was frequently co-expressed with HOXA9 in high-grade gliomas from TCGA, Oncomine, and our Portuguese and French datasets. Integrated in silico analyses, chromatin immunoprecipitation, and qPCR data showed that HOXA9 binds directly to the promoter of HOTAIR. Clinically, GBM patients with high HOTAIR expression had a significantly reduced overall survival, independently of other prognostic variables. In summary, this work reveals HOXA9 as a novel direct regulator of HOTAIR, and establishes HOTAIR as an independent prognostic marker, providing new therapeutic opportunities to treat this highly aggressive cancer. PMID:29644006

Predictive models and prognostic factors for upper tract urothelial carcinoma: a comprehensive review of the literature.

PubMed

Mbeutcha, Aurélie; Mathieu, Romain; Rouprêt, Morgan; Gust, Kilian M; Briganti, Alberto; Karakiewicz, Pierre I; Shariat, Shahrokh F

2016-10-01

In the context of customized patient care for upper tract urothelial carcinoma (UTUC), decision-making could be facilitated by risk assessment and prediction tools. The aim of this study was to provide a critical overview of existing predictive models and to review emerging promising prognostic factors for UTUC. A literature search of articles published in English from January 2000 to June 2016 was performed using PubMed. Studies on risk group stratification models and predictive tools in UTUC were selected, together with studies on predictive factors and biomarkers associated with advanced-stage UTUC and oncological outcomes after surgery. Various predictive tools have been described for advanced-stage UTUC assessment, disease recurrence and cancer-specific survival (CSS). Most of these models are based on well-established prognostic factors such as tumor stage, grade and lymph node (LN) metastasis, but some also integrate newly described prognostic factors and biomarkers. These new prediction tools seem to reach a high level of accuracy, but they lack external validation and decision-making analysis. The combinations of patient-, pathology- and surgery-related factors together with novel biomarkers have led to promising predictive tools for oncological outcomes in UTUC. However, external validation of these predictive models is a prerequisite before their introduction into daily practice. New models predicting response to therapy are urgently needed to allow accurate and safe individualized management in this heterogeneous disease.

Circulating Tumor Cell Count Correlates with Colorectal Neoplasm Progression and Is a Prognostic Marker for Distant Metastasis in Non-Metastatic Patients

NASA Astrophysics Data System (ADS)

Tsai, Wen-Sy; Chen, Jinn-Shiun; Shao, Hung-Jen; Wu, Jen-Chia; Lai-Ming, Jr.; Lu, Si-Hong; Hung, Tsung-Fu; Chiu, Yen-Chi; You, Jeng-Fu; Hsieh, Pao-Shiu; Yeh, Chien-Yuh; Hung, Hsin-Yuan; Chiang, Sum-Fu; Lin, Geng-Ping; Tang, Reiping; Chang, Ying-Chih

2016-04-01

Enumeration of circulating tumor cells (CTCs) has been proven as a prognostic marker for metastatic colorectal cancer (m-CRC) patients. However, the currently available techniques for capturing and enumerating CTCs lack of required sensitivity to be applicable as a prognostic marker for non-metastatic patients as CTCs are even more rare. We have developed a microfluidic device utilizing antibody-conjugated non-fouling coating to eliminate nonspecific binding and to promote the multivalent binding of target cells. We then established the correlation of CTC counts and neoplasm progression through applying this platform to capture and enumerate CTCs in 2 mL of peripheral blood from healthy (n = 27), benign (n = 21), non-metastatic (n = 95), and m-CRC (n = 15) patients. The results showed that the CTC counts progressed from 0, 1, 5, to 36. Importantly, after 2-year follow-up on the non-metastatic CRC patients, we found that those who had ≥5 CTCs were 8 times more likely to develop distant metastasis within one year after curable surgery than those who had <5. In conclusion, by employing a sensitive device, CTC counts show good correlation with colorectal neoplasm, thus CTC may be as a simple, independent prognostic marker for the non-metastatic CRC patients who are at high risk of early recurrence.

Full-length mutation search of the TP53 gene in acute myeloid leukemia has increased significance as a prognostic factor.

PubMed

Terada, Kazuki; Yamaguchi, Hiroki; Ueki, Toshimitsu; Usuki, Kensuke; Kobayashi, Yutaka; Tajika, Kenji; Gomi, Seiji; Kurosawa, Saiko; Miyadera, Keiki; Tokura, Taichiro; Omori, Ikuko; Marumo, Atushi; Fujiwara, Yusuke; Yui, Shunsuke; Ryotokuji, Takeshi; Osaki, Yoshiki; Arai, Kunihito; Kitano, Tomoaki; Kosaka, Fumiko; Wakita, Satoshi; Tamai, Hayato; Fukuda, Takahiro; Inokuchi, Koiti

2018-01-01

TP53 gene abnormality has been reported to be an unfavorable prognostic factor in acute myeloid leukemia (AML). However, almost all studies of TP53 gene abnormality so far have been limited to mutation searches in the DNA binding domain. As there have been few reports examining both mutation and deletion over the full-length of the TP53 gene, the clinical characteristics of TP53 gene abnormality have not yet been clearly established. In this study, TP53 gene mutation was observed in 7.3% of the total 412 de novo AML cases (33 mutations in 30 cases), with mutation outside the DNA binding domain in eight cases (27%). TP53 gene deletion was observed in 3.1% of 358 cases. All cases had monoallelic deletion with TP53 gene mutation on the opposite allele. Multivariate analysis demonstrated that TP53 gene mutation in the DNA binding domain and outside the DNA binding domain was an independent poor prognostic factor for overall survival and relapse-free survival among the total cohort and it is also an unfavorable prognostic factor in FLT3-ITD-negative AML cases aged 70 years or below with intermediate cytogenetic prognosis. In stratified treatment, full-length search for TP53 gene mutation is therefore very important.

Prognostics and health management design for rotary machinery systems—Reviews, methodology and applications

NASA Astrophysics Data System (ADS)

Lee, Jay; Wu, Fangji; Zhao, Wenyu; Ghaffari, Masoud; Liao, Linxia; Siegel, David

2014-01-01

Much research has been conducted in prognostics and health management (PHM), an emerging field in mechanical engineering that is gaining interest from both academia and industry. Most of these efforts have been in the area of machinery PHM, resulting in the development of many algorithms for this particular application. The majority of these algorithms concentrate on applications involving common rotary machinery components, such as bearings and gears. Knowledge of this prior work is a necessity for any future research efforts to be conducted; however, there has not been a comprehensive overview that details previous and on-going efforts in PHM. In addition, a systematic method for developing and deploying a PHM system has yet to be established. Such a method would enable rapid customization and integration of PHM systems for diverse applications. To address these gaps, this paper provides a comprehensive review of the PHM field, followed by an introduction of a systematic PHM design methodology, 5S methodology, for converting data to prognostics information. This methodology includes procedures for identifying critical components, as well as tools for selecting the most appropriate algorithms for specific applications. Visualization tools are presented for displaying prognostics information in an appropriate fashion for quick and accurate decision making. Industrial case studies are included in this paper to show how this methodology can help in the design of an effective PHM system.

Pharmacokinetic Tumor Heterogeneity as a Prognostic Biomarker for Classifying Breast Cancer Recurrence Risk.

PubMed

Mahrooghy, Majid; Ashraf, Ahmed B; Daye, Dania; McDonald, Elizabeth S; Rosen, Mark; Mies, Carolyn; Feldman, Michael; Kontos, Despina

2015-06-01

Heterogeneity in cancer can affect response to therapy and patient prognosis. Histologic measures have classically been used to measure heterogeneity, although a reliable noninvasive measurement is needed both to establish baseline risk of recurrence and monitor response to treatment. Here, we propose using spatiotemporal wavelet kinetic features from dynamic contrast-enhanced magnetic resonance imaging to quantify intratumor heterogeneity in breast cancer. Tumor pixels are first partitioned into homogeneous subregions using pharmacokinetic measures. Heterogeneity wavelet kinetic (HetWave) features are then extracted from these partitions to obtain spatiotemporal patterns of the wavelet coefficients and the contrast agent uptake. The HetWave features are evaluated in terms of their prognostic value using a logistic regression classifier with genetic algorithm wrapper-based feature selection to classify breast cancer recurrence risk as determined by a validated gene expression assay. Receiver operating characteristic analysis and area under the curve (AUC) are computed to assess classifier performance using leave-one-out cross validation. The HetWave features outperform other commonly used features (AUC = 0.88 HetWave versus 0.70 standard features). The combination of HetWave and standard features further increases classifier performance (AUCs 0.94). The rate of the spatial frequency pattern over the pharmacokinetic partitions can provide valuable prognostic information. HetWave could be a powerful feature extraction approach for characterizing tumor heterogeneity, providing valuable prognostic information.

SU-F-R-53: CT-Based Radiomics Analysis of Non-Small Cell Lung Cancer Patients Treated with Stereotactic Body Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huynh, E; Coroller, T; Narayan, V

Purpose: Stereotactic body radiation therapy (SBRT) is the standard of care for medically inoperable non-small cell lung cancer (NSCLC) patients and has demonstrated excellent local control and survival. However, some patients still develop distant metastases and local recurrence, and therefore, there is a clinical need to identify patients at high-risk of disease recurrence. The aim of the current study is to use a radiomics approach to identify imaging biomarkers, based on tumor phenotype, for clinical outcomes in SBRT patients. Methods: Radiomic features were extracted from free breathing computed tomography (CT) images of 113 Stage I-II NSCLC patients treated with SBRT.more » Their association to and prognostic performance for distant metastasis (DM), locoregional recurrence (LRR) and survival was assessed and compared with conventional features (tumor volume and diameter) and clinical parameters (e.g. performance status, overall stage). The prognostic performance was evaluated using the concordance index (CI). Multivariate model performance was evaluated using cross validation. All p-values were corrected for multiple testing using the false discovery rate. Results: Radiomic features were associated with DM (one feature), LRR (one feature) and survival (four features). Conventional features were only associated with survival and one clinical parameter was associated with LRR and survival. One radiomic feature was significantly prognostic for DM (CI=0.670, p<0.1 from random), while none of the conventional and clinical parameters were significant for DM. The multivariate radiomic model had a higher median CI (0.671) for DM than the conventional (0.618) and clinical models (0.617). Conclusion: Radiomic features have potential to be imaging biomarkers for clinical outcomes that conventional imaging metrics and clinical parameters cannot predict in SBRT patients, such as distant metastasis. Development of a radiomics biomarker that can identify patients at high-risk of recurrence could facilitate personalization of their treatment regimen for an optimized clinical outcome. R.M. had consulting interest with Amgen (ended in 2015).« less

Clinicopathological characteristics of triple negative breast cancer at a tertiary care hospital in India.

PubMed

Dogra, Atika; Doval, Dinesh Chandra; Sardana, Manjula; Chedi, Subhash Kumar; Mehta, Anurag

2014-01-01

Triple-negative breast cancer (TNBC), characterized by the lack of expression of estrogen receptor, progesterone receptor and human epidermal growth factor receptor-2, is typically associated with a poor prognosis. The majority of TNBCs show the expression of basal markers on gene expression profiling and most authors accept TNBC as basal-like (BL) breast cancer. However, a smaller fraction lacks a BL phenotype despite being TNBC. The literature is silent on non-basal-like (NBL) type of TNBC. The present study was aimed at defining behavioral differences between BL and NBL phenotypes. i) Identify the TNBCs and categorize them into BL and NBL breast cancer. ii) Examine the behavioral differences between two subtypes. iii) Observe the pattern of treatment failure among TNBCs. All TNBC cases during January 2009-December 2010 were retrieved. The subjects fitting the inclusion criteria of study were differentiated into BL and NBL phenotypes using surrogate immunohistochemistry with three basal markers 34βE12, c-Kit and EGFR as per the algorithm defined by Nielsen et al. The detailed data of subjects were collated from clinical records. The comparison of clinicopathological features between two subgroups was done using statistical analyses. The pattern of treatment failure along with its association with prognostic factors was assessed. TNBC constituted 18% of breast cancer cases considered in the study. The BL and NBL subtypes accounted for 81% and 19% respectively of the TNBC group. No statistically significant association was seen between prognostic parameters and two phenotypes. Among patients with treatment failure, 19% were with BL and 15% were with NBL phenotype. The mean disease free survival (DFS) in groups BL and NBL was 30.0 and 37.9 months respectively, while mean overall survival (OS) was 31.93 and 38.5 months respectively. Treatment failure was significantly associated with stage (p=.023) among prognostic factors. Disease stage at presentation is an important prognostic factor influencing the treatment failure and survival among TNBCs. Increasing tumor size is related to lymph node positivity. BL tumors have a more aggressive clinical course than that of NBL as shown by shorter DFS and OS, despite having no statistically significant difference between prognostic parameters. New therapeutic alternatives should be explored for patients with this subtype of breast cancer.

Sensor Systems for Prognostics and Health Management

PubMed Central

Cheng, Shunfeng; Azarian, Michael H.; Pecht, Michael G.

2010-01-01

Prognostics and health management (PHM) is an enabling discipline consisting of technologies and methods to assess the reliability of a product in its actual life cycle conditions to determine the advent of failure and mitigate system risk. Sensor systems are needed for PHM to monitor environmental, operational, and performance-related characteristics. The gathered data can be analyzed to assess product health and predict remaining life. In this paper, the considerations for sensor system selection for PHM applications, including the parameters to be measured, the performance needs, the electrical and physical attributes, reliability, and cost of the sensor system, are discussed. The state-of-the-art sensor systems for PHM and the emerging trends in technologies of sensor systems for PHM are presented. PMID:22219686

Sensor systems for prognostics and health management.

PubMed

Cheng, Shunfeng; Azarian, Michael H; Pecht, Michael G

2010-01-01

Prognostics and health management (PHM) is an enabling discipline consisting of technologies and methods to assess the reliability of a product in its actual life cycle conditions to determine the advent of failure and mitigate system risk. Sensor systems are needed for PHM to monitor environmental, operational, and performance-related characteristics. The gathered data can be analyzed to assess product health and predict remaining life. In this paper, the considerations for sensor system selection for PHM applications, including the parameters to be measured, the performance needs, the electrical and physical attributes, reliability, and cost of the sensor system, are discussed. The state-of-the-art sensor systems for PHM and the emerging trends in technologies of sensor systems for PHM are presented.

[The WHO/ISUP grading system for renal carcinoma].

PubMed

Moch, H

2016-07-01

Histological tumor grading is an accepted prognostic parameter of renal cell carcinoma (RCC). In 2012, the International Society of Urologic Pathologists (ISUP) proposed a novel grading system for RCC, mainly based on the evaluation of nucleoli: grade 1 tumors have nucleoli that are inconspicuous and basophilic at ×400 magnification; grade 2 tumors have nucleoli that are clearly visible at ×400 magnification and eosinophilic; grade 3 tumors have clearly visible nucleoli at ×100 magnification; and grade 4 tumors have extreme pleomorphism or rhabdoid and/or sarcomatoid morphology. This grading system was validated for clear cell renal cell carcinoma and papillary renal cell carcinoma. At the same time, the ISUP proposed not grading chromophobe renal cell carcinomas according to this system. At a consensus conference in Zurich the World Health Organization (WHO) recommended the ISUP grading system; thus, the WHO/ISUP grading system is now going to be implemented internationally. The ISUP/WHO grading system has not been validated as a prognostic parameter for other tumor subtypes, but can be used for descriptive purposes.

Prognostic value of a new cardiopulmonary exercise testing parameter in chronic heart failure: oxygen uptake efficiency at peak exercise - comparison with oxygen uptake efficiency slope.

PubMed

Toste, Alexandra; Soares, Rui; Feliciano, Joana; Andreozzi, Valeska; Silva, Sofia; Abreu, Ana; Ramos, Ruben; Santos, Ninel; Ferreira, Lurdes; Ferreira, Rui Cruz

2011-10-01

A growing body of evidence shows the prognostic value of oxygen uptake efficiency slope (OUES), a cardiopulmonary exercise test (CPET) parameter derived from the logarithmic relationship between O(2) consumption (VO(2)) and minute ventilation (VE) in patients with chronic heart failure (CHF). To evaluate the prognostic value of a new CPET parameter - peak oxygen uptake efficiency (POUE) - and to compare it with OUES in patients with CHF. We prospectively studied 206 consecutive patients with stable CHF due to dilated cardiomyopathy - 153 male, aged 53.3±13.0 years, 35.4% of ischemic etiology, left ventricular ejection fraction 27.7±8.0%, 81.1% in sinus rhythm, 97.1% receiving ACE-Is or ARBs, 78.2% beta-blockers and 60.2% spironolactone - who performed a first maximal symptom-limited treadmill CPET, using the modified Bruce protocol. In 33% of patients an cardioverter-defibrillator (ICD) or cardiac resynchronization therapy device (CRT-D) was implanted during follow-up. Peak VO(2), percentage of predicted peak VO(2), VE/VCO(2) slope, OUES and POUE were analyzed. OUES was calculated using the formula VO(2) (l/min) = OUES (log(10)VE) + b. POUE was calculated as pVO(2) (l/min) / log(10)peakVE (l/min). Correlation coefficients between the studied parameters were obtained. The prognosis of each variable adjusted for age was evaluated through Cox proportional hazard models and R2 percent (R2%) and V index (V6) were used as measures of the predictive accuracy of events of each of these variables. Receiver operating characteristic (ROC) curves from logistic regression models were used to determine the cut-offs for OUES and POUE. pVO(2): 20.5±5.9; percentage of predicted peak VO(2): 68.6±18.2; VE/VCO(2) slope: 30.6±8.3; OUES: 1.85±0.61; POUE: 0.88±0.27. During a mean follow-up of 33.1±14.8 months, 45 (21.8%) patients died, 10 (4.9%) underwent urgent heart transplantation and in three patients (1.5%) a left ventricular assist device was implanted. All variables proved to be independent predictors of this combined event; however, VE/VCO2 slope was most strongly associated with events (HR 11.14). In this population, POUE was associated with a higher risk of events than OUES (HR 9.61 vs. 7.01), and was also a better predictor of events (R2: 28.91 vs. 22.37). POUE was more strongly associated with death, urgent heart transplantation and implantation of a left ventricular assist device and proved to be a better predictor of events than OUES. These results suggest that this new parameter can increase the prognostic value of CPET in patients with CHF. Copyright © 2011 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

Quantitative immunohistochemistry of factor VIII-related antigen in breast carcinoma: a comparison of computer-assisted image analysis with established counting methods.

PubMed

Kohlberger, P D; Obermair, A; Sliutz, G; Heinzl, H; Koelbl, H; Breitenecker, G; Gitsch, G; Kainz, C

1996-06-01

Microvessel density in the area of the most intense neovascularization in invasive breast carcinoma is reported to be an independent prognostic factor. The established method of enumeration of microvessel density is to count the vessels using an ocular raster (counted microvessel density [CMVD]). The vessels were detected by staining endothelial cells using Factor VIII-related antigen. The aim of the study was to compare the CMVD results with the percentage of factor VIII-related antigen-stained area using computer-assisted image analysis. A true color red-green-blue (RGB) image analyzer based on a morphologically reduced instruction set computer processor was used to evaluate the area of stained endothelial cells. Sixty invasive breast carcinomas were included in the analysis. There was no significant correlation between the CMVD and the percentage of factor VIII-related antigen-stained area (Spearman correlation coefficient = 0.24, confidence interval = 0.02-0.46). Although high CMVD was significantly correlated with poorer recurrence free survival (P = .024), percentage of factor VIII-related antigen-stained area showed no prognostic value. Counted microvessel density and percentage of factor VIII-related antigen-stained area showed a highly significant correlation with vessel invasion (P = .0001 and P = .02, respectively). There was no correlation between CMVD and percentage of factor VIII-related antigen-stained area with other prognostic factors. In contrast to the CMVD within malignant tissue, the percentage of factor VIII-related antigen-stained area is not suitable as an indicator of prognosis in breast cancer patients.

Lactate Parameters Predict Clinical Outcomes in Patients with Nonvariceal Upper Gastrointestinal Bleeding.

PubMed

Lee, Seung Hoon; Min, Yang Won; Bae, Joohwan; Lee, Hyuk; Min, Byung Hoon; Lee, Jun Haeng; Rhee, Poong Lyul; Kim, Jae J

2017-11-01

The predictive role of lactate in patients with nonvariceal upper gastrointestinal bleeding (NVUGIB) has been suggested. This study evaluated several lactate parameters in terms of predicting outcomes of bleeding patients and sought to establish a new scoring model by combining lactate parameters and the AIMS65 score. A total of 114 patients with NVUGIB who underwent serum lactate level testing at least twice and endoscopic hemostasis within 24 hours after admission were retrospectively analyzed. The associations between five lactate parameters and clinical outcomes were evaluated and the predictive power of lactate parameter combined AIMS65s (L-AIMS65s) and AIMS56 scoring was compared. The most common cause of bleeding was gastric ulcer (48.2%). Lactate clearance rate (LCR) was associated with 30-day rebleeding (odds ratio [OR], 0.931; 95% confidence interval [CI], 0.872-0.994; P = 0.033). Initial lactate (OR, 1.313; 95% CI, 1.050-1.643; P = 0.017), maximal lactate (OR, 1.277; 95% CI, 1.037-1.573; P = 0.021), and average lactate (OR, 1.535; 95% CI, 1.137-2.072; P = 0.005) levels were associated with 30-day mortality. Initial lactate (OR, 1.213; 95% CI, 1.027-1.432; P = 0.023), maximal lactate (OR, 1.271; 95% CI, 1.074-1.504; P = 0.005), and average lactate (OR, 1.501; 95% CI, 1.150-1.959; P = 0.003) levels were associated with admission over 7 days. Although L-AIMS65s showed the highest area under the curve for prediction of each outcome, differences between L-AIMS65s and AIMS65 did not reach statistical significance. In conclusion, lactate parameters have a prognostic role in patients with NVUGIB. However, they do not increase the predictive power of AIMS65 when combined. © 2017 The Korean Academy of Medical Sciences.

[A prognostic model of a cholera epidemic].

PubMed

Boev, B V; Bondarenko, V M; Prokop'eva, N V; San Román, R T; Raygoza-Anaya, M; García de Alba, R

1994-01-01

A new model for the prognostication of cholera epidemic on the territory of a large city is proposed. This model reflects the characteristic feature of contacting infection by sensitive individuals due to the preservation of Vibrio cholerae in their water habitat. The mathematical model of the epidemic quantitatively reflects the processes of the spread of infection by kinetic equations describing the interaction of the streams of infected persons, the causative agents and susceptible persons. The functions and parameters of the model are linked with the distribution of individuals according to the duration of the incubation period and infectious process, as well as the period of asymptomatic carrier state. The computer realization of the model by means of IBM PC/AT made it possible to study the cholera epidemic which took place in Mexico in 1833. The verified model of the cholera epidemic was used for the prognostication of the possible spread of this infection in Guadalajara, taking into account changes in the epidemiological situation and the size of the population, as well as improvements in sanitary and hygienic conditions, in the city.

Clinical relevance of TRKA expression on neuroblastoma: comparison with N-MYC amplification and CD44 expression.

PubMed Central

Combaret, V.; Gross, N.; Lasset, C.; Balmas, K.; Bouvier, R.; Frappaz, D.; Beretta-Brognara, C.; Philip, T.; Favrot, M. C.; Coll, J. L.

1997-01-01

TRKA expression was evaluated on 122 untreated neuroblastomas by immunohistochemistry using an antibody with predetermined specificity. This procedure is simple and reliable for protein detection at cellular level in a routine clinical setting. Fourteen tumours were classified as benign ganglioneuroma with a restricted expression of TRKA on ganglion cells; these patients were excluded from the following analysis. A total of 108 tumours were classified as neuroblastoma or ganglioneuroblastoma; 74 expressed TRKA protein, which strongly correlated with low stage, absence of N-MYC amplification, age (<1 year), CD44 expression and favourable clinical outcome. In a univariate analysis including tumour stage, age, histology, N-MYC amplification, CD44 and TRKA expression, all parameters had significant prognostic value. The absence of TRKA expression on CD44-positive or N-MYC non-amplified tumours permits the characterization of a subgroup of patients with intermediate prognosis. However, in a multivariate analysis taking into consideration the prognostic factors mentioned above, CD44 and tumour stage were the only independent prognostic factors for the prediction of patients' event-free survival. PMID:9099963

Enhancing tumor apparent diffusion coefficient histogram skewness stratifies the postoperative survival in recurrent glioblastoma multiforme patients undergoing salvage surgery.

PubMed

Zolal, Amir; Juratli, Tareq A; Linn, Jennifer; Podlesek, Dino; Sitoci Ficici, Kerim Hakan; Kitzler, Hagen H; Schackert, Gabriele; Sobottka, Stephan B; Rieger, Bernhard; Krex, Dietmar

2016-05-01

Objective To determine the value of apparent diffusion coefficient (ADC) histogram parameters for the prediction of individual survival in patients undergoing surgery for recurrent glioblastoma (GBM) in a retrospective cohort study. Methods Thirty-one patients who underwent surgery for first recurrence of a known GBM between 2008 and 2012 were included. The following parameters were collected: age, sex, enhancing tumor size, mean ADC, median ADC, ADC skewness, ADC kurtosis and fifth percentile of the ADC histogram, initial progression free survival (PFS), extent of second resection and further adjuvant treatment. The association of these parameters with survival and PFS after second surgery was analyzed using log-rank test and Cox regression. Results Using log-rank test, ADC histogram skewness of the enhancing tumor was significantly associated with both survival (p = 0.001) and PFS after second surgery (p = 0.005). Further parameters associated with prolonged survival after second surgery were: gross total resection at second surgery (p = 0.026), tumor size (0.040) and third surgery (p = 0.003). In the multivariate Cox analysis, ADC histogram skewness was shown to be an independent prognostic factor for survival after second surgery. Conclusion ADC histogram skewness of the enhancing lesion, enhancing lesion size, third surgery, as well as gross total resection have been shown to be associated with survival following the second surgery. ADC histogram skewness was an independent prognostic factor for survival in the multivariate analysis.

Prevalence and prognostic significance of hyperkalemia in hospitalized patients with cirrhosis.

PubMed

Maiwall, Rakhi; Kumar, Suman; Sharma, Manoj Kumar; Wani, Zeeshan; Ozukum, Mulu; Sarin, Shiv Kumar

2016-05-01

The prevalence and clinical significance of hyponatremia in cirrhotics have been well studied; however, there are limited data on hyperkalemia in cirrhotics. We evaluated the prevalence and prognostic significance of hyperkalemia in hospitalized patients with cirrhosis and developed a prognostic model incorporating potassium for prediction of liver-related death in these patients. The training derivative cohort of patients was used for development of prognostic scores (Group A, n = 1160), which were validated in a large prospective cohort of cirrhotic patients. (Group B, n = 2681) of cirrhosis. Hyperkalemia was seen in 189 (14.1%) and 336 (12%) in Group A and Group B, respectively. Potassium showed a significant association that was direct with creatinine (P < 0.001) and urea (P < 0.001) and inverse with sodium (P < 0.001). Mortality was also significantly higher in patients with hyperkalemia (P = 0.0015, Hazard Ratio (HR) 1.3, 95% confidence interval 1.11-1.57). Combination of all these parameters into a single value predictor, that is, renal dysfunction index predicted mortality better than the individual components. Combining renal dysfunction index with other known prognostic markers (i.e. serum bilirubin, INR, albumin, hepatic encephalopathy, and ascites) in the "K" model predicted both short-term and long-term mortality with an excellent accuracy (Concordance-index 0.78 and 0.80 in training and validation cohorts, respectively). This was also superior to Model for End-stage Liver Disease, Model for End-stage liver disease sodium (MELDNa), and Child-Turcott-Pugh scores. Cirrhotics frequently have impaired potassium homeostasis, which has a prognostic significance. Serum potassium correlates directly with serum creatinine and urea and inversely with serum sodium. The model incorporating serum potassium developed from this study ("K"model) can predict death in advanced cirrhotics with an excellent accuracy. © 2015 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Prognostic value of circulating VEGFR2+ bone marrow-derived progenitor cells in patients with advanced cancer.

PubMed

Massard, Christophe; Borget, Isabelle; Le Deley, Marie Cécile; Taylor, Melissa; Gomez-Roca, Carlos; Soria, Jean Charles; Farace, Françoise

2012-06-01

We hypothesised that host-related markers, possibly reflecting tumour aggressiveness, such as circulating endothelial cells (CEC) and circulating VEGFR2(+) bone marrow-derived (BMD) progenitor cells, could have prognostic value in patients with advanced cancer enrolled in early anticancer drug development trials. Baseline CECs (CD45(-)CD31(+)CD146(+)7AAD(-) cells) and circulating VEGFR2(+)-BMD progenitor cells (defined as CD45(dim)CD34(+)VEGFR2(+)7AAD(-) cells) were measured by flow-cytometry in 71 and 58 patients included in phase 1 trials testing novel anti-vascular or anti-angiogenic agents. Correlations between levels of CECs, circulating VEGFR2(+)-BMD progenitor cells, clinical and biological prognostic factors (i.e. the Royal Marsden Hospital (RMH) score), and overall survival (OS) were studied. The median value of CECs was 12 CEC/ml (range 0-154/ml). The median level of VEGFR2(+)-BMD progenitor cells was 1.3% (range 0-32.5%) of circulating BMD-CD34(+) progenitors. While OS was not correlated with CEC levels, it was significantly worse in patients with high VEGFR2(+)-BMD progenitor levels (>1%) (median OS 9.0 versus 17.0 months), and with a RMH prognostic score >0 (median OS 9.0 versus 24.2 months). The prognostic value of VEGFR2(+)-BMD progenitor levels remained significant (hazard ratio (HR) = 2.3, 95% confidence interval (CI), 1.1-4.6, p = 0.02) after multivariate analysis. A composite VEGFR2(+)-BMD progenitor level/RHM score ≥ 2 was significantly associated with an increased risk of death compared to scores of 0 or 1 (median OS 9.0 versus 18.4 months, HR = 2.6 (95%CI, 1.2-5.8, p = 0.02)). High circulating VEGFR2(+)-BMD progenitor levels are associated with poor prognostics and when combined to classical clinical and biological parameters could provide a new tool for patient selection in early anticancer drug trials. Copyright © 2012 Elsevier Ltd. All rights reserved.

WE-E-17A-05: Complementary Prognostic Value of CT and 18F-FDG PET Non-Small Cell Lung Cancer Tumor Heterogeneity Features Quantified Through Texture Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Desseroit, M; Cheze Le Rest, C; Tixier, F

2014-06-15

Purpose: Previous studies have shown that CT or 18F-FDG PET intratumor heterogeneity features computed using texture analysis may have prognostic value in Non-Small Cell Lung Cancer (NSCLC), but have been mostly investigated separately. The purpose of this study was to evaluate the potential added value with respect to prognosis regarding the combination of non-enhanced CT and 18F-FDG PET heterogeneity textural features on primary NSCLC tumors. Methods: One hundred patients with non-metastatic NSCLC (stage I–III), treated with surgery and/or (chemo)radiotherapy, that underwent staging 18F-FDG PET/CT images, were retrospectively included. Morphological tumor volumes were semi-automatically delineated on non-enhanced CT using 3D SlicerTM.more » Metabolically active tumor volumes (MATV) were automatically delineated on PET using the Fuzzy Locally Adaptive Bayesian (FLAB) method. Intratumoral tissue density and FDG uptake heterogeneities were quantified using texture parameters calculated from co-occurrence, difference, and run-length matrices. In addition to these textural features, first order histogram-derived metrics were computed on the whole morphological CT tumor volume, as well as on sub-volumes corresponding to fine, medium or coarse textures determined through various levels of LoG-filtering. Association with survival regarding all extracted features was assessed using Cox regression for both univariate and multivariate analysis. Results: Several PET and CT heterogeneity features were prognostic factors of overall survival in the univariate analysis. CT histogram-derived kurtosis and uniformity, as well as Low Grey-level High Run Emphasis (LGHRE), and PET local entropy were independent prognostic factors. Combined with stage and MATV, they led to a powerful prognostic model (p<0.0001), with median survival of 49 vs. 12.6 months and a hazard ratio of 3.5. Conclusion: Intratumoral heterogeneity quantified through textural features extracted from both CT and FDG PET images have complementary and independent prognostic value in NSCLC.« less

The Diagnostic and Prognostic Value of Hematological and Chemical Abnormalities in Soft Tissue Sarcoma: A Comparative Study in Patients with Benign and Malignant Soft Tissue Tumors.

PubMed

Ariizumi, Takashi; Kawashima, Hiroyuki; Ogose, Akira; Sasaki, Taro; Hotta, Tetsuo; Hatano, Hiroshi; Morita, Tetsuro; Endo, Naoto

2018-01-01

The value of routine blood tests in malignant soft tissue tumors remains uncertain. To determine if these tests can be used for screening, the routine pretreatment blood test findings were retrospectively investigated in 359 patients with benign and malignant soft tissue tumors. Additionally, the prognostic potential of pretreatment blood abnormalities was evaluated in patients with soft tissue sarcomas. We compared clinical factors and blood tests findings between patients with benign and malignant soft tissue tumors using univariate and multivariate analysis. Subsequently, patients with malignant tumors were divided into two groups based on blood test reference values, and the prognostic significance of each parameter was evaluated. In the univariate analysis, age, tumor size, and tumor depth were significant clinical diagnostic factors. Significant increases in the granulocyte count, C-reactive protein (CRP) level, erythrocyte sedimentation rate (ESR), and γ-glutamyl transpeptidase (γ-GTP) levels were found in patients with malignant soft tissue tumors. Multiple logistic regression showed that tumor size and ESR were independent factors that predicted malignant soft tissue tumors. The Kaplan-Meier survival analysis revealed that granulocyte counts, γ-GTP levels, and CRP levels correlated significantly with overall survival. Thus, pretreatment routine blood tests are useful diagnostic and prognostic markers for diagnosing soft tissue sarcoma. © 2018 by the Association of Clinical Scientists, Inc.

Association Between Nutritional Status, Inflammatory Condition, and Prognostic Indexes with Postoperative Complications and Clinical Outcome of Patients with Gastrointestinal Neoplasia.

PubMed

Costa, Milena Damasceno de Souza; Vieira de Melo, Camila Yandara Sousa; Amorim, Ana Carolina Ribeiro de; Cipriano Torres, Dilênia de Oliveira; Dos Santos, Ana Célia Oliveira

2016-10-01

The aim of this study is to describe and relate nutritional and inflammatory status and prognostic indexes with postoperative complications and clinical outcome of patients with gastrointestinal malignancies. Twenty-nine patients were evaluated; nutritional assessment was carried out by subjective and objective parameters; albumin, pre-albumin, C-reactive protein (CRP), and alpha-1-acid glycoprotein (AGP) were determined. To assess prognosis, the Glasgow scale, the Prognostic Inflammatory Nutritional Index (PINI), and CRP/albumin ratio were used; the clinical outcomes considered were hospital discharge and death. A high Subjective Global Assessment (SGA) score was associated with the occurrence of postoperative complications: 73% of the patients with postoperative complications had the highest SGA score, but only 6% of those without postoperative complications had the highest SGA score (P < 0.001). Greater occurrence of death was observed in patients with a high SGA score, low serum albumin, increased CRP, PINI > 1, and Glasgow score 2. There was a positive correlation between weight loss percentage with serum CRP levels (P = 0.002), CRP/albumin (P = 0.002), PINI (P = 0.002), and Glasgow score (P = 0.000). This study provides evidence that the assessment of the nutritional status and the use of prognostic indexes are good tools for predicting postoperative complications and clinical outcome in patients with gastrointestinal neoplasia.

The Prognostic Nutritional Index Predicts Survival and Identifies Aggressiveness of Gastric Cancer.

PubMed

Eo, Wan Kyu; Chang, Hye Jung; Suh, Jungho; Ahn, Jin; Shin, Jeong; Hur, Joon-Young; Kim, Gou Young; Lee, Sookyung; Park, Sora; Lee, Sanghun

2015-01-01

Nutritional status has been associated with long-term outcomes in cancer patients. The prognostic nutritional index (PNI) is calculated by serum albumin concentration and absolute lymphocyte count, and it may be a surrogate biomarker for nutritional status and possibly predicts overall survival (OS) of gastric cancer. We evaluated the value of the PNI as a predictor for disease-free survival (DFS) in addition to OS in a cohort of 314 gastric cancer patients who underwent curative surgical resection. There were 77 patients in PNI-low group (PNI ≤ 47.3) and 237 patients in PNI-high group (PNI > 47.3). With a median follow-up of 36.5 mo, 5-yr DFS rates in PNI-low group and PNI-high group were 63.5% and 83.6% and 5-yr OS rates in PNI-low group and PNI-high group were 63.5% and 88.4%, respectively (DFS, P < 0.0001; OS, P < 0.0001). In the multivariate analysis, the only predictors for DFS were PNI, tumor-node-metastasis (TNM) stage, and perineural invasion, whereas the only predictors for OS were PNI, age, TNM stage, and perineural invasion. In addition, the PNI was independent of various inflammatory markers. In conclusion, the PNI is an independent prognostic factor for both DFS and OS, and provides additional prognostic information beyond pathologic parameters.

Cytogenetic abnormalities and their prognostic significance in idiopathic myelofibrosis: a study of 106 cases.

PubMed

Reilly, J T; Snowden, J A; Spearing, R L; Fitzgerald, P M; Jones, N; Watmore, A; Potter, A

1997-07-01

The prognostic significance of cytogenetic abnormalities was determined in 106 patients with well-characterized idiopathic myelofibrosis who were successfully karyotyped at diagnosis. 35% of the cases exhibited a clonal abnormality (37/106), whereas 65% (69/106) had a normal karyotype. Three characteristic defects, namely del(13q) (nine cases), del(20q) (eight cases) and partial trisomy 1q (seven cases), were present in 64.8% (24/37) of patients with clonal abnormalities. Kaplan-Meier plots and log rank analysis demonstrated an abnormal karyotype to be an adverse prognostic variable (P<0.001). Of the eight additional clinical and haematological parameters recorded at diagnosis, age (P<0.01), anaemia (haemoglobin < or = 10 g/dl: P<0.001), platelet (< or = 100 x 10(9)/l, P<0.0001) and leucocyte count (> 10.3 x 10(9)/l; P=0.06) were also associated with a shorter survival. In contrast, sex, spleen and liver size, and percentage blast cells were not found to be significant. Multivariate analysis, using Cox's regression, revealed karyotype, haemoglobin concentration, platelet and leucocyte counts to retain their unfavourable prognostic significance. A simple and useful schema for predicting survival in idiopathic myelofibrosis has been produced by combining age, haemoglobin concentration and karyotype with median survival times varying from 180 months (good-risk group) to 16 months (poor-risk group).

Intensity and Pattern of Enhancement on CESM: Prognostic Significance and its Relation to Expression of Podoplanin in Tumor Stroma - A Preliminary Report.

PubMed

Luczynska, Elzbieta; Niemiec, Joanna; Heinze, Sylwia; Adamczyk, Agnieszka; Ambicka, Aleksandra; Marcyniuk, Paulina; Rudnicki, Wojciech; Mitus, Jerzy W; Dyczek, Sonia; Rys, Janusz; Sas-Korczynska, Beata

2018-02-01

It is possible that the degree of enhancement on contrast-enhanced spectral mammography (CESM), a new diagnostic method, might provide prognostic information for breast cancer patients. Therefore, in a group of 82 breast cancer patients, we analyzed the prognostic significance of degree and pattern of enhancement on CESM as well as its relation to: (a) breast cancer immunophenotype (based on ER/PR/HER2 status) (b) podoplanin expression in cancer stroma (lymphatic vessel density plus podoplanin-positivity of cancer-associated fibroblasts), and (c) other histological parameters. For each tumor the intensity of enhancement on CESM was qualitatively assessed as strong or weak/medium, while the pattern - as homogenous and heterogenous. Herein we report, for the first time, that strong and heterogenous enhancement on CESM was related to unfavorable disease-free survival of breast cancer patients (p=0.005). Moreover, the strong enhancement was more frequent in large and node-positive tumors (pT>1, pN>0) (p=0.002), as well as in carcinomas with podoplanin-sparse stroma (p=0.008). Intensity and pattern of enhancement on CESM might provide (together with the results of other diagnostic imaging methods) not only the confirmation of presence or absence of tumor, but also prognostic information. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

External validation of leukocytosis and neutrophilia as a prognostic marker in anal carcinoma treated with definitive chemoradiation.

PubMed

Schernberg, Antoine; Huguet, Florence; Moureau-Zabotto, Laurence; Chargari, Cyrus; Rivin Del Campo, Eleonor; Schlienger, Michel; Escande, Alexandre; Touboul, Emmanuel; Deutsch, Eric

2017-07-01

To validate the prognostic value of leukocyte disorders in anal squamous cell carcinoma (SCC) patients receiving definitive concurrent chemoradiation. Bi-institutional clinical records from consecutive patients treated between 2001 and 2015 with definitive chemoradiation for anal SCC were retrospectively reviewed. Prognostic value of pretreatment leukocyte disorders was examined, with focus on patterns of relapse and survival. Leukocytosis and neutrophilia were defined as leukocyte or neutrophil count exceeding 10G/L and 7G/L, respectively. We identified 133 patients, treated in two institutions. Eight% and 7% displayed baseline leukocytosis and neutrophilia, respectively. Estimated 3-year overall survival (OS) and progression-free survival (PFS) were 88% and 77%, respectively. In univariate analysis, both leukocytosis and neutrophilia were associated with worse OS, PFS (p<0.01), locoregional control (LRC) and Distant Metastasis Control (DMC) (p<0.05), also after stratification by each institution. In multivariate analysis, leukocytosis and neutrophilia remained as independent risk factors associated with poorer OS, PFS, LRC and DMC (p<0.05). This study validates leukocytosis and neutrophilia as independent prognostic factors in anal SCC patients treated with definitive chemoradiation. Although prospective confirmation is warranted, it is suggested that the leukocyte and neutrophil count parameters are clinically relevant biomarkers to be considered for further clinical investigations. Copyright © 2017 Elsevier B.V. All rights reserved.

HPV RNA CISH score identifies two prognostic groups in a p16 positive oropharyngeal squamous cell carcinoma population.

PubMed

Augustin, Jérémy; Mandavit, Marion; Outh-Gauer, Sophie; Grard, Ophélie; Gasne, Cassandre; Lépine, Charles; Mirghani, Haïtham; Hans, Stéphane; Bonfils, Pierre; Denize, Thomas; Bruneval, Patrick; Bishop, Justin A; Fontugne, Jacqueline; Péré, Hélène; Tartour, Eric; Badoual, Cécile

2018-06-20

HPV-related and HPV-unrelated oropharyngeal squamous cell carcinomas are two distinct entities according to the Union for International Cancer Control, with a better prognosis conferred to HPV-related oropharyngeal squamous cell carcinomas. However, variable clinical outcomes are observed among patients with p16 positive oropharyngeal squamous cell carcinoma, which is a surrogate marker of HPV infection. We aimed to investigate the prognostic value of RNA CISH against E6 and E7 transcripts (HPV RNA CISH) to predict such variability. We retrospectively included 50 histologically confirmed p16 positive oropharyngeal squamous cell carcinomas (p16 positive immunostaining was defined by a strong staining in 70% or more of tumor cells). HPV RNA CISH staining was assessed semi-quantitatively to define two scores: RNA CISH "low" and RNA CISH "high". Negative HPV RNA CISH cases were scored as RNA CISH "low". This series contained 29 RNA CISH low cases (58%) and 21 RNA CISH high cases (42%). Clinical and pathologic baseline characteristics were similar between the two groups. RNA CISH high staining was associated with a better overall survival in both univariate and multivariate analyses (p = 0.033 and p = 0.042, respectively). Other recorded parameters had no prognostic value. In conclusion, HPV RNA CISH might be an independent prognostic marker in p16 positive oropharyngeal squamous cell carcinomas and might help guide therapeutics.

Development of an On-board Failure Diagnostics and Prognostics System for Solid Rocket Booster

NASA Technical Reports Server (NTRS)

Smelyanskiy, Vadim N.; Luchinsky, Dmitry G.; Osipov, Vyatcheslav V.; Timucin, Dogan A.; Uckun, Serdar

2009-01-01

We develop a case breach model for the on-board fault diagnostics and prognostics system for subscale solid-rocket boosters (SRBs). The model development was motivated by recent ground firing tests, in which a deviation of measured time-traces from the predicted time-series was observed. A modified model takes into account the nozzle ablation, including the effect of roughness of the nozzle surface, the geometry of the fault, and erosion and burning of the walls of the hole in the metal case. The derived low-dimensional performance model (LDPM) of the fault can reproduce the observed time-series data very well. To verify the performance of the LDPM we build a FLUENT model of the case breach fault and demonstrate a good agreement between theoretical predictions based on the analytical solution of the model equations and the results of the FLUENT simulations. We then incorporate the derived LDPM into an inferential Bayesian framework and verify performance of the Bayesian algorithm for the diagnostics and prognostics of the case breach fault. It is shown that the obtained LDPM allows one to track parameters of the SRB during the flight in real time, to diagnose case breach fault, and to predict its values in the future. The application of the method to fault diagnostics and prognostics (FD&P) of other SRB faults modes is discussed.

Prognostic value of preoperative serum CA 242 in Esophageal squamous cell carcinoma cases.

PubMed

Feng, Ji-Feng; Huang, Ying; Chen, Qi-Xun

2013-01-01

Carbohydrate antigen (CA) 242 is inversely related to prognosis in many cancers. However, few data regarding CA 242 in esophageal cancer (EC) are available. The aim of this study was to determine the prognostic value of CA 242 and propose an optimum cut-off point in predicting survival difference in patients with esophageal squamous cell carcinoma (ESCC). A retrospective analysis was conducted of 192 cases. A receiver operating characteristic (ROC) curve for survival prediction was plotted to verify the optimum cuf- off point. Univariate and multivariate analyses were performed to evaluate prognostic parameters for survival. The positive rate for CA 242 was 7.3% (14/192). The ROC curve for survival prediction gave an optimum cut-off of 2.15 (U/ml). Patients with CA 242 ≤ 2.15 U/ml had significantly better 5-year survival than patients with CA 242 >2.15 U/ml (45.4% versus 22.6%; P=0.003). Multivariate analysis showed that differentiation (P=0.033), CA 242 (P=0.017), T grade (P=0.004) and N staging (P<0.001) were independent prognostic factors. Preoperative CA 242 is a predictive factor for long-term survival in ESCC, especially in nodal-negative patients. We conclude that 2.15 U/ml may be the optimum cuf-off point for CA 242 in predicting survival in ESCC.

Prognostic significance of Fas and Fas ligand system-associated apoptosis in gastric cancer.

PubMed

Ohno, S; Tachibana, M; Shibakita, M; Dhar, D K; Yoshimura, H; Kinugasa, S; Kubota, H; Masunaga, R; Nagasue, N

2000-12-01

Previous studies indicate that gastric carcinomas express Fas ligand and down-regulate Fas to escape from the host immune attack; however, the prognostic importance of Fas/FasL expression in this tumor is yet to be evaluated. Specimens from 87 gastric carcinoma patients of different stages treated in a defined period with curative intent were evaluated for apoptosis, Fas, FasL, and CD8 expression using an immunohistochemical method. The percentage of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive apoptotic cells expressed as apoptotic index (AI) was higher in 43 patients when the cut-off value was set at the median value. There were no significant correlations between AI and clinicopathologic parameters. Thirty-nine patients showed a high number of CD8+ cells within cancer nests. Positive FasL and Fas expression was seen in 53 and 72 patients, respectively. CD8 and FasL expressions were related only to patients' age. Fas expression had significant correlations with tumor invasion and Lauren classification. There were significant direct correlations between AI and number of nest CD8+ cells and between AI and grade of Fas expression. Apoptotic index, pT stage, CD8 expression, and Fas expression were identified as independent prognostic factors. Spontaneous apoptosis in gastric carcinoma may be an independent prognosticator for survival and is significantly influenced by tumor Fas expression and number of nest CD8 + cells.

Echocardiographic assessment of right ventricular function in routine practice: Which parameters are useful to predict one-year outcome in advanced heart failure patients with dilated cardiomyopathy?

PubMed

Kawata, Takayuki; Daimon, Masao; Kimura, Koichi; Nakao, Tomoko; Lee, Seitetsu L; Hirokawa, Megumi; Kato, Tomoko S; Watanabe, Masafumi; Yatomi, Yutaka; Komuro, Issei

2017-10-01

Right ventricular (RV) function has recently gained attention as a prognostic predictor of outcome even in patients who have left-sided heart failure. Since several conventional echocardiographic parameters of RV systolic function have been proposed, our aim was to determine if any of these parameters (tricuspid annular plane systolic excursion: TAPSE, tissue Doppler derived systolic tricuspid annular motion velocity: S', fractional area change: FAC) are associated with outcome in advanced heart failure patients with dilated cardiomyopathy (DCM). We retrospectively enrolled 68 DCM patients, who were New York Heart Association (NYHA) Class III or IV and had a left ventricular (LV) ejection fraction <35%. All patients were undergoing evaluation for heart transplantation or management of heart failure. Primary outcomes were defined as LV assist device implantation or cardiac death within one year. Thirty-nine events occurred (5 deaths, 32 LV assist devices implanted). Univariate analysis showed that age, systolic blood pressure, heart rate, NYHA functional class IV, plasma brain natriuretic peptide concentration, intravenous inotrope use, left atrial volume index, and FAC were associated with outcome, whereas TAPSE and S' were not. Receiver-operating characteristic curve analysis showed that the optimal FAC cut-off value to identify patients with an event was <26.7% (area under the curve=0.74). The event-free rate determined by Kaplan-Meier analysis was significantly higher in patients with FAC≥26.7% than in those with FAC<26.7% (log-lank, p=0.0003). Moreover, the addition of FAC<26.7% improved the prognostic utility of a model containing clinical variables and conventional echocardiographic indexes. FAC may provide better prognostic information than TAPSE or S' in advanced heart failure patients with DCM. Copyright © 2017 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

The Anatomical Biological Value on Pretreatment (18)F-fluorodeoxyglucose Positron Emission Tomography Computed Tomography Predicts Response and Survival in Locally Advanced Head and Neck Cancer.

PubMed

Ashamalla, Hani; Mattes, Malcolm; Guirguis, Adel; Zaidi, Arifa; Mokhtar, Bahaa; Tejwani, Ajay

2014-05-01

(18)F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) has become increasingly relevant in the staging of head and neck cancers, but its prognostic value is controversial. The objective of this study was to evaluate different PET/CT parameters for their ability to predict response to therapy and survival in patients treated for head and neck cancer. A total of 28 consecutive patients with a variety of newly diagnosed head and neck cancers underwent PET/CT scanning at our institution before initiating definitive radiation therapy. All underwent a posttreatment PET/CT to gauge tumor response. Pretreatment PET/CT parameters calculated include the standardized uptake value (SUV) and the anatomical biological value (ABV), which is the product of SUV and greatest tumor diameter. Maximum and mean values were studied for both SUV and ABV, and correlated with response rate and survival. The mean pretreatment tumor ABVmax decreased from 35.5 to 7.9 (P = 0.0001). Of the parameters tested, only pretreatment ABVmax was significantly different among those patients with a complete response (CR) and incomplete response (22.8 vs. 65, respectively, P = 0.021). This difference was maximized at a cut-off ABVmax of 30 and those patients with ABVmax < 30 were significantly more likely to have a CR compared to those with ABVmax of ≥ 30 (93.8% vs. 50%, respectively, P = 0.023). The 5-year overall survival was 80% compared to 36%, respectively, (P = 0.028). Multivariate analysis confirmed that ABVmax was an independent prognostic factor. Our data supports the use of PET/CT, and specifically ABVmax, as a prognostic factor in head and neck cancer. Patients who have an ABVmax ≥ 30 were more likely to have a poor outcome with chemoradiation alone, and a more aggressive trimodality approach may be indicated in these patients.

Correlation of HER-2 over-expression with clinico-pathological parameters in Tunisian breast carcinoma

PubMed Central

Ayadi, Lobna; Khabir, Abdelmajid; Amouri, Habib; Karray, Sondes; Dammak, Abdallah; Guermazi, Mohamed; Boudawara, Tahya

2008-01-01

Background Breast carcinoma is a disease with a tremendous heterogeneity in its clinical behavior. Newer prognostic factors and predictors of response to therapy are needed. The aim of this study was to evaluate the expression of HER-2, estrogen receptor (ER) and progesterone receptors (PR) in breast carcinoma and to compare it with other prognostic parameters such as histological type and grade, tumor size, patients' age, and lymph node metastases. Patients and methods This is a retrospective study conducted in the department of pathology at Sfax University Hospital. Confirmed 155 Cases of breast carcinoma were reviewed in the period between January 2000 and December 2004. We used immunohistochemistry to evaluate the expression of HER-2, ER, and PR receptor and Chi-square and Fisher exact test to correlate immunohistochemical findings with prognostic parameters for breast carcinoma such as patients' age, tumor size, histological type, histological grade and lymph node status. Results The mean age of patients was 51.5 years, ranging from 22 to 89 years. 80 (51.6%) of the patients were below 50 years. The percentage of expression of HER-2, ER and PR was 26, 59.4, and 52.3%, respectively. HER-2 was over-expressed (3+) in 18.1% of the cases, was inversely related to ER expression (p = 0.00) and to PR expression (p = 0.048). This over-expression was also associated with a high tumor grade with marginal significance (p = 0.072). A negative correlation was noted between ER and PR expression and SBR grade (p = 0.000) and ER and age (p = 0.002). Conclusion HER-2 over-expression was observed in 18.1% of Tunisian breast carcinoma affecting female patients. This group presents apparently an aggressive form of breast carcinoma with high histological grade and negative ER. PMID:18945339

Impact of paranasal sinus invasion on advanced nasopharyngeal carcinoma treated with intensity-modulated radiation therapy: the validity of advanced T stage of AJCC/UICC eighth edition staging system.

PubMed

Wang, Ying; Zhao, Jie; Zhao, Yajie; Yang, Zhen; Lei, Mingjun; Li, Zhanzhan; Wei, Rui; Chen, Dengming; He, Yuxiang; Shen, Liangfang

2018-05-01

The aim of this study was to clarify the prognostic role of paranasal sinus invasion in advanced NPC patients. Data of patients (n = 295) with advanced NPC (T3/T4N0-3 M0) treated with intensity-modulated radiation therapy were retrospectively analyzed. Staging was according to the AJCC/UICC eighth edition staging system. Overall survival (OS), local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and disease-free survival (DFS) were calculated, and differences were compared between patients with and without paranasal sinus invasion. Multivariate analysis was used to identify the independent predictors of different survival parameters. Paranasal sinus invasion was present in 126 of 295 (42.7%) patients. Sphenoid, ethmoid, maxillary, and frontal sinus involvements were present in 123 of 295 (41.7%), 95 of 295 (32.2%), 45 of 295 (15.3%), and 0 of 295 (0%), respectively. All survival parameters were significantly better in patients without paranasal sinus invasion. When paranasal sinus invasion was reclassified as T4 instead of T3, all survival rates, other than LRFS (P = 0.156), were significantly better in the new T3 patients, and differences in all survival parameters remained nonsignificant between T3 with paranasal sinus invasion and T4 without paranasal sinus invasion patients (all P > 0.05). In multivariate analysis, paranasal sinus invasion was found to be an independent negative prognostic factor for OS, DFS, and DMFS (P = 0.016, P = 0.004, and P = 0.006, respectively), but not for LRFS (P = 0.068). Paranasal sinus invasion has prognostic value in advanced NPC. It may be reasonable to classify paranasal sinus invasion as T4 stage. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Analysis of histological and immunological parameters of metastatic lymph nodes from colon cancer patients reveals that T-helper 1 type immune response is associated with improved overall survival.

PubMed

Nizri, Eran; Greenman-Maaravi, Nofar; Bar-David, Shoshi; Ben-Yehuda, Amir; Weiner, Gilad; Lahat, Guy; Klausner, Joseph

2016-11-01

Lymph node (LN) involvement in colonic carcinoma (CC) is a grave prognostic sign and mandates the addition of adjuvant treatment. However, in light of the histological variability and outcomes observed, we hypothesized that patients with LN metastases (LNM) comprise different subgroups.We retrospectively analyzed the histological sections of 82 patients with CC and LNM. We studied various histological parameters (such as tumor grade, desmoplasia, and preservation of LN architecture) as well as the prevalence of specific peritumoral immune cells (CD8, CD20, T-bet, and GATA-3). We correlated the histological and immunological data to patient outcome.Tumor grade was a significant prognostic factor even in patients with LNM. So was the number of LN involved (N1/N2 stage). From the morphological parameters tested (LN extracapsular invasion, desmoplasia in LN, LN architecture preservation, and mode of metastases distribution), none was found to be significantly associated with overall survival (OS). The mean OS of CD8 low patients was 66.6 ± 6.25 versus 71.4 ± 5.1 months for CD8 high patients (P = 0.79). However, T-helper (Th) 1 immune response skewing (measured by Th1/Th2 ratio >1) was significantly associated with improved OS. For patients with low ratio, the median OS was 35.5 ± 5 versus 83.5 months for patients with high Th1/Th2 ratio (P = 0.001).The histological presentation of LNM does not entail specific prognostic information. However, the finding of Th1 immune response in LN signifies a protective immune response. Future studies should be carried to verify this marker and develop a strategy that augments this immune response during subsequent adjuvant treatment.

Cardiac Troponin Is a Predictor of Septic Shock Mortality in Cancer Patients in an Emergency Department: A Retrospective Cohort Study.

PubMed

Yang, Zhi; Qdaisat, Aiham; Hu, Zhihuang; Wagar, Elizabeth A; Reyes-Gibby, Cielito; Meng, Qing H; Yeung, Sai-Ching J

2016-01-01

Septic shock may be associated with myocardial damage; however, the prognostic value of cardiac enzymes in cancer patients with septic shock is unknown. In this study, we evaluated the prognostic significance of cardiac enzymes in combination with established prognostic factors in predicting the 7-day mortality rate of patients with septic shock, and we constructed a new scoring system, Septic Oncologic Patients in Emergency Department (SOPED), which includes cardiac enzymes, to predict 7-day mortality rates. We performed a retrospective cohort study of 375 adult cancer patients with septic shock who visited the emergency department of a comprehensive cancer center between 01/01/2004 and 12/31/2013. The 7-day and 28-day mortality rates were 19.7% and 37.6%, respectively. The creatine kinase myocardial band fraction and troponin-I were significantly higher in patients who died in ≤7 days and ≤28 days than in those who did not. In Cox regression models, troponin-I >0.05 ng/mL plus Predisposition, Infection, Response, and Organ Failure (PIRO2011) or Mortality in Emergency Department Sepsis (MEDS) score was a significant predictor of survival for ≤7 days. With our new SOPED scoring system, the receiver operating characteristic area under the curve was 0.836, higher than those for PIRO2011 and MEDS. Troponin-I >0.05 ng/mL was an important predictor of short-term mortality (≤7 days). The SOPED scoring system, which incorporated troponin-I, was more prognostically accurate than were other scores for 7-day mortality. Large multicenter studies are needed to verify our results and prospectively validate the prognostic performance of the SOPED score.

Tumor-infiltrating Neutrophils is Prognostic and Predictive for Postoperative Adjuvant Chemotherapy Benefit in Patients With Gastric Cancer.

PubMed

Zhang, Heng; Liu, Hao; Shen, Zhenbin; Lin, Chao; Wang, Xuefei; Qin, Jing; Qin, Xinyu; Xu, Jiejie; Sun, Yihong

2018-02-01

This study was aimed to investigate the prognostic value of tumor-infiltrating neutrophils (TINs) and to generate a predictive model to refine postoperative risk stratification system for patients with gastric cancer. TIN presents in various malignant tumors, but its clinical significance in gastric cancer remains obscure. The study enrolled 3 independent sets of patients with gastric cancer from 2 institutional medical centers of China. TIN was estimated by immunohistochemical staining of CD66b, and its relationship with clinicopathological features and clinical outcomes were evaluated. Prognostic accuracies were evaluated by C-index and Akaike information criterion. TINs in gastric cancer tissues ranged from 0 to 192 cells/high magnification filed (HPF), 0 to 117 cells/HPF, and 0 to 142 cells/HPF in the training, testing, and validation sets, respectively. TINs were negatively correlated with lymph node classification (P = 0.007, P = 0.041, and P = 0.032, respectively) and tumor stage (P = 0.019, P = 0.013, and P = 0.025, respectively) in the 3 sets. Moreover, multivariate analysis identified TINs and tumor node metastasis (TNM) stage as 2 independent prognostic factors for overall survival. Incorporation of TINs into well-established TNM system generated a predictive model that shows better predictive accuracy for overall survival. More importantly, patients with higher TINs were prone to overall survival benefit from postoperative adjuvant chemotherapy. These results were validated in the independent testing and validation sets. TIN in gastric cancer was identified as an independent prognostic factor, which could be incorporated into standard TNM staging system to refine risk stratification and predict for overall survival benefit from postoperative chemotherapy in patients with gastric cancer.

Thai venous stroke prognostic score: TV-SPSS.

PubMed

Poungvarin, Niphon; Prayoonwiwat, Naraporn; Ratanakorn, Disya; Towanabut, Somchai; Tantirittisak, Tassanee; Suwanwela, Nijasri; Phanthumchinda, Kamman; Tiamkoa, Somsak; Chankrachang, Siwaporn; Nidhinandana, Samart; Laptikultham, Somsak; Limsoontarakul, Sansern; Udomphanthuruk, Suthipol

2009-11-01

Prognosis of cerebral venous sinus thrombosis (CVST) has never been studied in Thailand. A simple prognostic score to predict poor prognosis of CVST has also never been reported. The authors are aiming to establish a simple and reliable prognostic score for this condition. The medical records of CVST patients from eight neurological training centers in Thailand who received between April 1993 and September 2005 were reviewed as part of this retrospective study. Clinical features included headache, seizure, stroke risk factors, Glasgow coma scale (GCS), blood pressure on arrival, papilledema, hemiparesis, meningeal irritation sign, location of occluded venous sinuses, hemorrhagic infarction, cerebrospinal fluid opening pressure, treatment options, length of stay, and other complications were analyzed to determine the outcome using modified Rankin scale (mRS). Poor prognosis (defined as mRS of 3-6) was determined on the discharge date. One hundred ninety four patients' records, 127 females (65.5%) and mean age of 36.6 +/- 14.4 years, were analyzed Fifty-one patients (26.3%) were in the poor outcome group (mRS 3-6). Overall mortality was 8.4%. Univariate analysis and then multivariate analysis using SPSS version 11.5 revealed only four statistically significant predictors influencing outcome of CVST They were underlying malignancy, low GCS, presence of hemorrhagic infarction (for poor outcome), and involvement of lateral sinus (for good outcome). Thai venous stroke prognostic score (TV-SPSS) was derived from these four factors using a multiple logistic model. A simple and pragmatic prognostic score for CVST outcome has been developed with high sensitivity (93%), yet low specificity (33%). The next study should focus on the validation of this score in other prospective populations.

Tumour budding activity and cell nest size determine patient outcome in oral squamous cell carcinoma: proposal for an adjusted grading system.

PubMed

Boxberg, Melanie; Jesinghaus, Moritz; Dorfner, Christiane; Mogler, Carolin; Drecoll, Enken; Warth, Arne; Steiger, Katja; Bollwein, Christine; Meyer, Petra; Wolff, Klaus D; Kolk, Andreas; Weichert, Wilko

2017-06-01

Oral squamous cell carcinoma (OSCC) is a common malignancy with a variable clinical course. One of the established survival predictors in carcinomas in general is tumour grade; in OSCC, however, grading according to the World Health Organization (WHO) has no independent prognostic impact. Recently, a novel grading scheme associated with high impact on patient outcome has been proposed for squamous cell carcinoma of the lung. To probe whether this scheme could be applied to the upper aerodigestive tract, we retrospectively evaluated 157 chemo- and radiotherapy-naive OSCCs with complete clinical follow-up data and standardized treatment for tumour budding activity (BA), cell nest size (CNS), extent of keratinization, stromal content, nuclear size and mitotic count. Histomorphological characteristics were correlated with clinicopathological data and patient outcome. As in squamous cell carcinoma of the lung, high BA and small CNS were correlated significantly with shortened overall, disease-specific and disease-free survival. A three-tiered grading system based on a sum score of these two prognostic markers proved to be a strong age-, stage- and sex-independent prognosticator for survival with a hazard ratio for overall survival of 2.1 for intermediately differentiated (G2) tumours and 3.4 for poorly differentiated (G3) tumours compared to well-differentiated (G1) tumours (P < 0.001). We recapitulated and validated almost exactly the strong prognostic impact of a grading algorithm proposed recently for squamous cell carcinoma of the lung in OSCC. Our data may pave the way for a prognostically highly relevant future squamous cell carcinoma grading system broadly applicable in the aerodigestive tract. © 2017 John Wiley & Sons Ltd.

Prognostic impact of number of resected and involved lymph nodes at complete resection on survival in non-small cell lung cancer.

PubMed

Saji, Hisashi; Tsuboi, Masahiro; Yoshida, Koichi; Kato, Yasufumi; Nomura, Masaharu; Matsubayashi, Jun; Nagao, Toshitaka; Kakihana, Masatoshi; Usuda, Jitsuo; Kajiwara, Naohiro; Ohira, Tatsuo; Ikeda, Norihiko

2011-11-01

Lymph node (LN) status is a major determinant of stage and survival in patients with lung cancer. In the 7th edition of the TNM Classification of Malignant Tumors, the number of involved LNs is included in the definition of pN factors in breast, stomach, esophageal, and colorectal cancer, and the pN status significantly correlates with prognosis. We retrospectively investigated the prognostic impact of the number of resected LNs (RLNs) and involved LNs in the context of other established clinical prognostic factors, in a series of 928 consecutive patients with non-small cell lung cancer (NSCLC) who underwent complete resection at our institution between 2000 and 2007. The mean number of RLNs was 15. There was a significant difference in the total number of RLNs categorized between less than 10 and ≥10 (p = 0.0129). Although the incidence of LN involvement was statistically associated with poor prognosis, the largest statistically significant increase in overall survival was observed between 0 to 3 and ≥4 involved LNs (hazard ratio = 7.680; 95% confidence interval = 5.051-11.655, p < 0.0001). On multivariate analysis, we used the ratio between the number of involved LNs and RLNs. The number of RLNs was found to be a strong independent prognostic factor for NSCLC (hazard ratio = 6.803; 95% confidence interval = 4.137-11.186, p < 0.0001). Complete resection including 10 or more LNs influenced survival at complete NSCLC resection. Four involved LNs seemed to be a benchmark for NSCLC prognosis. The number of involved LNs is a strong independent prognostic factor in NSCLC, and the results of this study may provide new information for determining the N category in the next tumor, node, metastasis classification.

Preferences for Life-Sustaining Treatments and Associations With Accurate Prognostic Awareness and Depressive Symptoms in Terminally Ill Cancer Patients' Last Year of Life.

PubMed

Tang, Siew Tzuh; Wen, Fur-Hsing; Hsieh, Chia-Hsun; Chou, Wen-Chi; Chang, Wen-Cheng; Chen, Jen-Shi; Chiang, Ming-Chu

2016-01-01

The stability of life-sustaining treatment (LST) preferences at end of life (EOL) has been established. However, few studies have assessed preferences more than two times. Furthermore, associations of LST preferences with modifiable variables of accurate prognostic awareness, physician-patient EOL care discussions, and depressive symptoms have been investigated in cross-sectional studies only. To explore longitudinal changes in LST preferences and their associations with accurate prognostic awareness, physician-patient EOL care discussions, and depressive symptoms in terminally ill cancer patients' last year. LST preferences (cardiopulmonary resuscitation, intensive care unit [ICU] care, intubation, and mechanical ventilation) were measured approximately every two weeks. Changes in LST preferences and their associations with independent variables were examined by hierarchical generalized linear modeling with logistic regression. Participants (n = 249) predominantly rejected cardiopulmonary resuscitation, ICU care, intubation, and mechanical ventilation at EOL without significant changes as death approached. Patients with inaccurate prognostic awareness were significantly more likely than those with accurate understanding to prefer ICU care, intubation, and mechanical ventilation than to reject these LSTs. Patients with more severe depressive symptoms were less likely to prefer ICU care and to be undecided about wanting ICU care and mechanical ventilation than to reject such LSTs. LST preferences were not associated with physician-patient EOL care discussions, which were rare in our sample. LST preferences are stable in cancer patients' last year. Facilitating accurate prognostic awareness and providing adequate psychological support may counteract the increasing trend for aggressive EOL care and minimize emotional distress during EOL care decisions. Copyright © 2016 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

Google Goes Cancer: Improving Outcome Prediction for Cancer Patients by Network-Based Ranking of Marker Genes

PubMed Central

Roy, Janine; Aust, Daniela; Knösel, Thomas; Rümmele, Petra; Jahnke, Beatrix; Hentrich, Vera; Rückert, Felix; Niedergethmann, Marco; Weichert, Wilko; Bahra, Marcus; Schlitt, Hans J.; Settmacher, Utz; Friess, Helmut; Büchler, Markus; Saeger, Hans-Detlev; Schroeder, Michael; Pilarsky, Christian; Grützmann, Robert

2012-01-01

Predicting the clinical outcome of cancer patients based on the expression of marker genes in their tumors has received increasing interest in the past decade. Accurate predictors of outcome and response to therapy could be used to personalize and thereby improve therapy. However, state of the art methods used so far often found marker genes with limited prediction accuracy, limited reproducibility, and unclear biological relevance. To address this problem, we developed a novel computational approach to identify genes prognostic for outcome that couples gene expression measurements from primary tumor samples with a network of known relationships between the genes. Our approach ranks genes according to their prognostic relevance using both expression and network information in a manner similar to Google's PageRank. We applied this method to gene expression profiles which we obtained from 30 patients with pancreatic cancer, and identified seven candidate marker genes prognostic for outcome. Compared to genes found with state of the art methods, such as Pearson correlation of gene expression with survival time, we improve the prediction accuracy by up to 7%. Accuracies were assessed using support vector machine classifiers and Monte Carlo cross-validation. We then validated the prognostic value of our seven candidate markers using immunohistochemistry on an independent set of 412 pancreatic cancer samples. Notably, signatures derived from our candidate markers were independently predictive of outcome and superior to established clinical prognostic factors such as grade, tumor size, and nodal status. As the amount of genomic data of individual tumors grows rapidly, our algorithm meets the need for powerful computational approaches that are key to exploit these data for personalized cancer therapies in clinical practice. PMID:22615549

Pre-Treatment Anemia Is a Poor Prognostic Factor in Soft Tissue Sarcoma Patients

PubMed Central

Szkandera, Joanna; Gerger, Armin; Liegl-Atzwanger, Bernadette; Stotz, Michael; Samonigg, Hellmut; Ploner, Ferdinand; Stojakovic, Tatjana; Leithner, Andreas; Pichler, Martin

2014-01-01

Background Anemia refers to low hemoglobin (Hb) levels, represents a common symptom and complication in cancer patients and was reported to negatively influence survival in patients with various malignancies. In the present study, we aimed to explore the prognostic impact of pre-operative Hb levels on clinical outcome in a large cohort of soft tissue sarcoma (STS) patients after curative surgery. Methods Retrospective data from 367 STS patients, which were operated between 1998 and 2013, were included in the study. Cut-off levels for anemia were defined as Hb<13 g/dl in males and Hb<12 g/dl in females according to the current WHO guidelines. The impact of pre-operative Hb levels on cancer-specific survival (CSS) and overall survival (OS) was assessed using Kaplan-Meier curves. Additionally, Hb levels were compared for the prognostic influence on CSS and OS applying univariate and multivariate Cox proportional models. Results Hb level was associated with established prognostic factors, including age, tumor grade, size and depth (p<0.05). Kaplan-Meier curves showed that low Hb levels were significantly associated with decreased CSS and OS in STS patients (p<0.001 for both endpoints, log-rank test). In multivariate analysis, we found an independent association between low Hb levels and poor CSS and OS (HR = 0.46, Cl 95% = 0.25–0.85, p = 0.012; HR = 0.34, Cl 95% = 0.23–0.51, p<0.001). Conclusion The present data underline a negative prognostic impact of low pre-operative Hb levels on clinical outcome in STS patients. Thus, Hb levels may provide an additional and cost-effective tool to discriminate between STS patients that are at high risk of mortality. PMID:25207808

Development of a prognostic scale for severely hemiplegic stroke patients in a rehabilitation hospital.

PubMed

Hirano, Yoshitake; Nitta, Osamu; Hayashi, Takeshi; Takahashi, Hidetoshi; Miyazaki, Yasuhiro; Kigawa, Hiroshi

2017-07-01

For patients with severe hemiplegia in a rehabilitation hospital, early prediction of the functional prognosis and outcomes is challenging. The purpose of this study was to create and verify a prognostic scale in severely hemiplegic stroke patients and allowing for prediction of (1) the ability to walk at the time of hospital discharge, (2) the ability to carry out activities of daily living (ADL), and (3) feasibility of home discharge. The study was conducted on 80 severely hemiplegic stroke patients. A prognostic scale was created as an analysis method using the following items: mini-mental state examination (MMSE) at the time of admission, modified NIH stroke scale (m-NIHSS); trunk control test (TCT); and the ratio of the knee extensor strength on the non-paralyzed side to the body weight (KES/BW-US). We verified the reliability and validity of this scale. We established a prognostic scale using the MMSE, m-NIHSS, TCT, and KES/BW-US. A score of 56.8 or higher on the prognostic scale suggested that the patient would be able to walk and that assistance with ADL would be unnecessary at the time of hospital discharge. In addition, a score of 41.3 points indicated that the patient's return home was feasible. The reliability and the results were in good agreement. These findings showed that the ability or inability to walk was predictable in 85%, the need of assistance with ADL in 82.5%, and the feasibility of home return in 76.3% of cases. At the time of admission, four evaluation items permitted the prediction of three outcomes at time of discharge. Our formula predicts three outcomes with an accuracy of more than 76%. Copyright © 2017 Elsevier B.V. All rights reserved.

The prognostic value of reactive stroma on prostate needle biopsy: a population-based study.

PubMed

Saeter, Thorstein; Vlatkovic, Ljiljana; Waaler, Gudmund; Servoll, Einar; Nesland, Jahn M; Axcrona, Karol; Axcrona, Ulrika

2015-05-01

Reactive tumor stroma has been shown to play an active role in prostatic carcinogenesis. A grading system for reactive stroma in prostate cancer (PC) has recently been established and found to predict biochemical recurrence and prostate cancer-specific mortality (PCSM) in prostatectomized patients. To the best of our knowledge, there has been no study investigating the prognostic value of reactive stromal grading (RSG) with regard to PCSM when evaluated in diagnostic prostate needle biopsies. A population-based study on 318 patients, encompassing all cases of PC diagnosed by needle biopsies and without evidence of systemic metastasis at the time of diagnosis in Aust-Agder County in the period 1991-1999. Patients were identified by cross-referencing the Cancer Registry of Norway. Clinical data were obtained by review of medical charts. The endpoint was PCSM. RSG was evaluated on haematoxylin and eosin stained sections according to previously described criteria; grade 0, 0-5% reactive stroma; grade 1, 6-15%; grade 2, 16-50%; grade 3, 51-100%. RSG could be evaluated in 278 patients. The median follow- up time was 110 months (interquartile range: 51-171). The 10-year PC - specific survival rate for RSGs of 0, 1, 2, and 3 was 96%, 81%, 69%, and 63%, respectively (P < 0.005). RSG remained independently associated with PCSM in a multivariate Cox regression analysis adjusting for prostate-specific antigen level, clinical stage, Gleason score, and mode of treatment. The concordance index of the multivariate model was 0.814 CONCLUSIONS: Our study demonstrates that RSG in diagnostic prostate needle biopsies predicts PCSM independently of other evaluable prognostic factors. Hence, RSG could be used in addition to traditional prognostic factors for prognostication and treatment stratification of PC patients. © 2015 Wiley Periodicals, Inc.

[Interaction of oxytocin, laser and electromagnetic radiation on the persistence properties of Staphylococcus aureus].

PubMed

Kurlaev, P P; Chernova, O L; Kirgizova, S B

2000-01-01

The suppressive action of oxytocin, heliumneon radiation and ultrahigh-frequency electromagnetic waves (UHF-therapy) on the persistence properties of S. aureus has been experimentally established. The effectiveness of the therapeutic actions under study in the treatment of patients with the prognosticated unfavorable course of purulent inflammatory diseases of soft tissues has been shown.

Up regulation of the steroid hormone synthesis regulator HSD3B2 is linked to early PSA recurrence in prostate cancer.

PubMed

Neubauer, Emily; Latif, Morwari; Krause, Jenny; Heumann, Asmus; Armbrust, Moritz; Luehr, Clara; Fraune, Christoph; Hube-Magg, Claudia; Kluth, Martina; Möller-Koop, Christina; Sauter, Guido; Simon, Ronald; Beyer, Burkhard; Pompe, Raisa S; Thederan, Imke; Schlomm, Thorsten; Büscheck, Franziska

2018-05-24

HSD3B2 plays a crucial role in steroid hormone biosynthesis and is thus of particular interest in hormone dependent tumors such as prostate cancer. To clarify the clinical relevance of HSD3B2 expression in prostate cancer, we analyzed HSD3B2 protein expression by immunohistochemistry on our preexisting tissue microarray with 12.247 annotated cancers. Compared with normal tissue cytoplasmic HSD3B2 staining was stronger in prostate cancers. In 9371 interpretable cancers, HSD3B2 expression was found in 95.5% of cancers and was considered weak in 29.9%, moderate in 40.7% and strong in 24.9%. HSD3B2 up regulation was linked to advanced pathological tumor stage (pT), high Gleason grade, elevated preoperative PSA levels (p < 0.0001 each), lymph node metastasis (p = 0.0019), accelerated cell proliferation (p < 0.0001), androgen receptor (AR) expression (p < 0.0001), and early biochemical recurrence (p < 0.0001). HSD3B2 up regulation was only marginally more frequent in ERG positive (98%) than in ERG negative cancers (94%; p < 0.0001) and was strongly linked to deletions of 5q and 6q (p < 0.0001 each). Multivariate analyses showed that the prognostic impact of HSD3B2 expression was independent of established preoperative, but not of postoperative prognostic parameters. In summary, the results of our study demonstrate that HSD3B2 is strongly up regulated in a fraction of prostate cancers that are characterized by increased AR signaling, adverse tumor phenotype and early biochemical recurrence. Copyright © 2018 Elsevier Inc. All rights reserved.

Tumour-specific HMG-CoAR is an independent predictor of recurrence free survival in epithelial ovarian cancer.

PubMed

Brennan, Donal J; Brändstedt, Jenny; Rexhepaj, Elton; Foley, Michael; Pontén, Fredrik; Uhlén, Mathias; Gallagher, William M; O'Connor, Darran P; O'Herlihy, Colm; Jirstrom, Karin

2010-04-01

Our group previously reported that tumour-specific expression of the rate-limiting enzyme in the mevalonate pathway, 3-hydroxy-3-methylglutharyl-coenzyme A reductase (HMG-CoAR) is associated with more favourable tumour parameters and a good prognosis in breast cancer. In the present study, the prognostic value of HMG-CoAR expression was examined in tumours from a cohort of patients with primary epithelial ovarian cancer. HMG-CoAR expression was assessed using immunohistochemistry (IHC) on tissue microarrays (TMA) consisting of 76 ovarian cancer cases, analysed using automated algorithms to develop a quantitative scoring model. Kaplan Meier analysis and Cox proportional hazards modelling were used to estimate the risk of recurrence free survival (RFS). Seventy-two tumours were suitable for analysis. Cytoplasmic HMG-CoAR expression was present in 65% (n = 46) of tumours. No relationship was seen between HMG-CoAR and age, histological subtype, grade, disease stage, estrogen receptor or Ki-67 status. Patients with tumours expressing HMG-CoAR had a significantly prolonged RFS (p = 0.012). Multivariate Cox regression analysis revealed that HMG-CoAR expression was an independent predictor of improved RFS (RR = 0.49, 95% CI (0.25-0.93); p = 0.03) when adjusted for established prognostic factors such as residual disease, tumour stage and grade. HMG-CoAR expression is an independent predictor of prolonged RFS in primary ovarian cancer. As HMG-CoAR inhibitors, also known as statins, have demonstrated anti-neoplastic effects in vitro, further studies are required to evaluate HMG-CoAR expression as a surrogate marker of response to statin treatment, especially in conjunction with current chemotherapeutic regimens.

Tumour-specific HMG-CoAR is an independent predictor of recurrence free survival in epithelial ovarian cancer

PubMed Central

2010-01-01

Background Our group previously reported that tumour-specific expression of the rate-limiting enzyme in the mevalonate pathway, 3-hydroxy-3-methylglutharyl-coenzyme A reductase (HMG-CoAR) is associated with more favourable tumour parameters and a good prognosis in breast cancer. In the present study, the prognostic value of HMG-CoAR expression was examined in tumours from a cohort of patients with primary epithelial ovarian cancer. Methods HMG-CoAR expression was assessed using immunohistochemistry (IHC) on tissue microarrays (TMA) consisting of 76 ovarian cancer cases, analysed using automated algorithms to develop a quantitative scoring model. Kaplan Meier analysis and Cox proportional hazards modelling were used to estimate the risk of recurrence free survival (RFS). Results Seventy-two tumours were suitable for analysis. Cytoplasmic HMG-CoAR expression was present in 65% (n = 46) of tumours. No relationship was seen between HMG-CoAR and age, histological subtype, grade, disease stage, estrogen receptor or Ki-67 status. Patients with tumours expressing HMG-CoAR had a significantly prolonged RFS (p = 0.012). Multivariate Cox regression analysis revealed that HMG-CoAR expression was an independent predictor of improved RFS (RR = 0.49, 95% CI (0.25-0.93); p = 0.03) when adjusted for established prognostic factors such as residual disease, tumour stage and grade. Conclusion HMG-CoAR expression is an independent predictor of prolonged RFS in primary ovarian cancer. As HMG-CoAR inhibitors, also known as statins, have demonstrated anti-neoplastic effects in vitro, further studies are required to evaluate HMG-CoAR expression as a surrogate marker of response to statin treatment, especially in conjunction with current chemotherapeutic regimens. PMID:20359358

Impact of Preoperative Abdominal Visceral Adipose Tissue Area and Nutritional Status on Renal Function After Donor Nephrectomy in Japanese Living Donors for Renal Transplantation.

PubMed

Hori, Shunta; Miyake, Makito; Morizawa, Yosuke; Nakai, Yasushi; Onishi, Kenta; Iida, Kota; Gotoh, Daisuke; Anai, Satoshi; Torimoto, Kazumasa; Aoki, Katsuya; Yoneda, Tatsuo; Tanaka, Nobumichi; Yoshida, Katsunori; Fujimoto, Kiyohide

2018-05-29

BACKGROUND Living kidney donors face the risk of renal dysfunction, resulting in end-stage renal disease, cardiovascular disease, or cerebrovascular disease, after donor nephrectomy. Reducing this risk is important to increasing survival of living donors. In this study, we investigated the effect of preoperative distribution of abdominal adipose tissue and nutritional status on postoperative renal function in living donors. MATERIAL AND METHODS Seventy-five living donors were enrolled in this retrospective study. Preoperative unenhanced computed tomography images were used to measure abdominal adipose tissue parameters. Prognostic nutritional index (PNI) was used to assess preoperative nutritional status. Donors were divided into 2 groups according to abdominal visceral adipose tissue (VAT) area at the level of the fourth and fifth lumbar vertebrae (<80 or ≥80 cm²). Postoperative renal function was compared in the 2 groups, and prognostic factors for development of chronic kidney disease (CKD) G3b were identified using multivariate analysis. RESULTS Donors with a VAT area ≥80 significantly more often had hypertension preoperatively. Although there was no significant difference in preoperative estimated glomerular filtration rate (eGFR) between the 2 groups, postoperative renal function was significantly decreased in donors with a VAT area ≥80 compared to those with a VAT area <80. In multivariate analysis, VAT area ≥80 and PNI <54 were independent factors predicting the development of CKD G3b after 12 months. CONCLUSIONS Our findings suggest that preoperative VAT and PNI affect postoperative renal function. Further research is required to establish appropriate exercise protocols and nutritional interventions during follow-up to improve outcomes in living donors.

An overview of the applied definitions and diagnostic methods to assess exercise oscillatory ventilation--a systematic review.

PubMed

Cornelis, Justien; Beckers, Paul; Vanroy, Christel; Volckaerts, Tess; Vrints, Christiaan; Vissers, Dirk

2015-01-01

The variable "exercise oscillatory ventilation" (EOV), assessed during cardiopulmonary exercise test (CPET), recently became a fundamental prognostic parameter in patients with heart failure. In literature, various definitions are suggested, but an uniformly accepted description to identify EOV still lacks. We performed a systematic review of the literature in order to determine the different definitions and diagnostic techniques to assess EOV. A systematic search strategy was established and executed in seven databases (PubMed, Google Scholar, Cochrane Clinical Trials, Science Direct, Pedro, Web Of Science library and Medline (Ovid)) resulting in 605 citations after de-duplication. Full-text articles (n=124) were assessed for eligibility, resulting in 75 citations. The review accounted 17,440 patients of whom 4,638 subjects presented EOV. Seven studies described EOV in a non-heart failure population accounting 168 EOV subjects. The definitions could be categorized in nine subdivisions of which four (n=43) referred to an original description. The other subdivisions were combinations of the original definitions (n=11), quantifications (n=4), computational (n=3), vaguely described (n=8) or not defined (n=6). Symptom limited maximal exercise tests were conducted to assess EOV, however the modes, protocols, software and data sampling were divers. Heterogeneity in the numerous definitions to identify EOV and the vaguely described assessment methods are hindering the evolution to a standardized uniformly accepted definition and technique to identify this abnormal breathing pattern. Unity in definition and international adopted assessment is warranted to strengthen its validity as a prognostic marker and could promote communication. It may facilitate clinical trials on pathophysiology and origin of EOV. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Mucinous Colorectal Adenocarcinoma: Influence of EGFR and E-Cadherin Expression on Clinicopathologic Features and Prognosis.

PubMed

Foda, Abd AlRahman M; AbdelAziz, Azza; El-Hawary, Amira K; Hosni, Ali; Zalata, Khalid R; Gado, Asmaa I

2015-08-01

Previous studies have shown conflicting results on epidermal growth factor receptor (EGFR) and E-cadherin expression in colorectal carcinoma and their prognostic significance. To the best of our knowledge, this study is the first to investigate EGFR and E-cadherin expression, interrelation and relation to clinicopathologic, histologic parameters, and survival in rare colorectal mucinous adenocarcinoma (MA). In this study, we studied tumor tissue specimens from 150 patients with colorectal MA and nonmucinous adenocarcinoma (NMA). High-density manual tissue microarrays were constructed using modified mechanical pencil tips technique, and immunohistochemistry for EGFR and E-cadherin was performed. All relations were analyzed using established statistical methodologies. NMA expressed EGFR and E-cadherin in significantly higher rates with significant heterogenous pattern than MA. EGFR and E-cadherin positivity rates were significantly interrelated in both NMA and MA groups. In the NMA group, high EGFR expression was associated with old age, male sex, multiplicity of tumors, lack of mucinous component, and association with schistosomiasis. However, in the MA group, high EGFR expression was associated only with old age and MA subtype rather than signet ring carcinoma subtype. Conversely, high E-cadherin expression in MA cases was associated with old age, fungating tumor configuration, MA subtype, and negative intratumoral lymphocytic response. However, in the NMA cases, none of these factors was statistically significant. In a univariate analysis, neither EGFR nor E-cadherin expression showed a significant impact on disease-free or overall survival. Targeted therapy against EGFR and E-cadherin may not be useful in patients with MA. Neither EGFR nor E-cadherin is an independent prognostic factor in NMA or MA.

PD-1 (PDCD1) Promoter Methylation Is a Prognostic Factor in Patients With Diffuse Lower-Grade Gliomas Harboring Isocitrate Dehydrogenase (IDH) Mutations.

PubMed

Röver, Lea Kristin; Gevensleben, Heidrun; Dietrich, Jörn; Bootz, Friedrich; Landsberg, Jennifer; Goltz, Diane; Dietrich, Dimo

2018-02-01

Immune checkpoints are important targets for immunotherapies. However, knowledge on the epigenetic modification of immune checkpoint genes is sparse. In the present study, we investigated promoter methylation of CTLA4, PD-L1, PD-L2, and PD-1 in diffuse lower-grade gliomas (LGG) harboring isocitrate dehydrogenase (IDH) mutations with regard to mRNA expression levels, clinicopathological parameters, previously established methylation subtypes, immune cell infiltrates, and survival in a cohort of 419 patients with IDH-mutated LGG provided by The Cancer Genome Atlas. PD-L1, PD-L2, and CTLA-4 mRNA expression levels showed a significant inverse correlation with promoter methylation (PD-L1: p=0.005; PD-L2: p<0.001; CTLA-4: p<0.001). Furthermore, immune checkpoint methylation was significantly associated with age (PD-L2: p=0.003; PD-1: p=0.015), molecular alterations, i.e. MGMT methylation (PD-L1: p<0.001; PD-L2: p<0.001), ATRX mutations (PD-L2: p<0.001, PD-1: p=0.001), and TERT mutations (PD-L1: p=0.035, PD-L2: p<0.001, PD-1: p<0.001, CTLA4: p<0.001) as well as methylation subgroups and immune cell infiltrates. In multivariate Cox proportional hazard analysis, PD-1 methylation qualified as strong prognostic factor (HR=0.51 [0.34-0.76], p=0.001). Our findings suggest an epigenetic regulation of immune checkpoint genes via DNA methylation in LGG. PD-1 methylation may assist the identification of patients that might benefit from an alternative treatment, particularly in the context of emerging immunotherapies. Copyright © 2018 The Author(s). Published by Elsevier B.V. All rights reserved.

Prognostic Value of Electrocardiographic Left Ventricular Hypertrophy on Cardiovascular Risk in a Non-hypertensive Community-based Population.

PubMed

Tanaka, Kentaro; Tanaka, Fumitaka; Onoda, Toshiyuki; Tanno, Kozo; Ohsawa, Masaki; Sakata, Kiyomi; Omama, Shinichi; Ogasawara, Kuniaki; Ishibashi, Yasuhiro; Itai, Kazuyoshi; Kuribayashi, Toru; Okayama, Akira; Nakamura, Motoyuki

2018-04-06

The appearance of left ventricular hypertrophy on 12-lead electrocardiography (ECG-LVH) has been clarified to be associated with the risk of incidence of cardiovascular events (CVEs) in hypertensive individuals and the general population, but not enough in non-hypertensive individuals. A total of 4,927 non-hypertensive individuals ≥ 40 years of age who were free of CVE in the general population were followed for the incidence of CVE. ECG-LVH was defined according to criteria of the Sokolow-Lyon (SL) voltage, Cornell voltage (CV), or Cornell voltage product (CP). During the average 9.8 ± 2.0 years of follow-up, 267 individuals (5.4%) had their first CVE. The hazard ratio (HR) for the incidence of CVE after full adjustment by potential confounders significantly increased in the individuals with ECG-LVH by any criteria of the SL voltage, CV, and CP (HR = 1.77, p < 0.001) compared to those with no ECG-LVH. This association was significant also in individuals without any of obesity, dyslipidemia, and diabetes mellitus or those with systolic BP <120 mmHg and diastolic BP < 80mmHg. Furthermore, ECG-LVH by each criteria provided the reclassification improvement for the CVE risk prediction model by the Framingham 10-year risk score (the net reclassification improvement = 0.17 to 0.22, each p value < 0.010). In the absence of hypertension, ECG-LVH parameters are associated with the increased risk of developed CVEs independent of the established risk factors and provide the additional prognostic value in an assessment of the CVE risk using the traditional risk factors.

Prognostic impact of c-Rel nuclear expression and REL amplification and crosstalk between c-Rel and the p53 pathway in diffuse large B-cell lymphoma

PubMed Central

Ok, Chi Young; Tzankov, Alexandar; Manyam, Ganiraju C.; Sun, Ruifan; Visco, Carlo; Zhang, Mingzhi; Montes-Moreno, Santiago; Dybkaer, Karen; Chiu, April; Orazi, Attilio; Zu, Youli; Bhagat, Govind; Richards, Kristy L.; Hsi, Eric D.; Choi, William W.L.; van Krieken, J. Han; Huh, Jooryung; Ponzoni, Maurilio; Ferreri, Andrés J.M.; Møller, Michael B.; Wang, Jinfeng; Parsons, Ben M.; Winter, Jane N.; Piris, Miguel A.; Pham, Lan V.; Medeiros, L. Jeffrey; Young, Ken H.

2015-01-01

Dysregulated NF-κB signaling is critical for lymphomagenesis. The regulation, function, and clinical relevance of c-Rel/NF-κB activation in diffuse large B-cell lymphoma (DLBCL) have not been well studied. In this study we analyzed the prognostic significance and gene-expression signature of c-Rel nuclear expression as surrogate of c-Rel activation in 460 patients with de novo DLBCL. Nuclear c-Rel expression, observed in 137 (26.3%) DLBCL patients frequently associated with extranoal origin, did not show significantly prognostic impact in the overall- or germinal center B-like-DLBCL cohort, likely due to decreased pAKT and Myc levels, up-regulation of FOXP3, FOXO3, MEG3 and other tumor suppressors coincided with c-Rel nuclear expression, as well as the complicated relationships between NF-κB members and their overlapping function. However, c-Rel nuclear expression correlated with significantly poorer survival in p63+ and BCL-2− activated B-cell-like-DLBCL, and in DLBCL patients with TP53 mutations. Multivariate analysis indicated that after adjusting clinical parameters, c-Rel positivity was a significantly adverse prognostic factor in DLBCL patients with wild type TP53. Gene expression profiling suggested dysregulations of cell cycle, metabolism, adhesion, and migration associated with c-Rel activation. In contrast, REL amplification did not correlate with c-Rel nuclear expression and patient survival, likely due to co-amplification of genes that negatively regulate NF-κB activation. These insights into the expression, prognostic impact, regulation and function of c-Rel as well as its crosstalk with the p53 pathway underscore the importance of c-Rel and have significant therapeutic implications. PMID:26324762

Comparison of the AJCC, MSTS, and Modified Spanier Systems for Clinical and Pathologic Staging of Osteosarcoma.

PubMed

Cates, Justin M M

2017-03-01

The prognostic performance of the 2 most commonly used staging systems for skeletal sarcoma (the American Joint Committee on Cancer [AJCC] and Musculoskeletal Tumor Society [MSTS] systems) have never been compared analytically. Another staging system originally proposed by Spanier has not yet been validated. Given the recent release of the 8th edition of the AJCC Cancer Staging Manual, this study was designed to directly compare these anatomic staging systems in a series of 153 high-grade, intramedullary osteosarcomas. Kaplan-Meier curves were plotted and pairwise comparisons between each stage category were performed. Predictive accuracy of each staging system for determining 5-year disease-free survival was evaluated by comparing areas under receiver-operating characteristic curves generated from logistic regression analysis. Multiple concordance indices were calculated using bootstrapping methods (200 replications). ρk and R were estimated as measures of the variation in survival outcomes explained by the regression models. The AJCC, MSTS, and a modified version of the Spanier staging systems showed similar discriminatory abilities and no significant differences in the levels of contrast between different tumor stages across staging systems. Addition of T-category information from each staging system contributed significant prognostic information compared with a Cox proportional hazard regression model consisting only of the presence or absence of metastatic disease as a measure of disease extent. Concordance indices and predictive accuracy for 5-year disease-free survival were not significantly different among the different staging systems either. Similar findings were observed after accounting for other important prognostic variables. Additional studies are necessary to determine performance parameters of each staging system for other types of skeletal sarcoma. Prognostic performance of osteosarcoma staging systems would also be improved by incorporating nonanatomic prognostic variables into staging algorithms.

Clinicopathologic and prognostic significance of C-reactive protein/albumin ratio in patients with solid tumors: an updated systemic review and meta-analysis.

PubMed

Wu, Jiayuan; Tan, Wenkai; Chen, Lin; Huang, Zhe; Mai, Shao

2018-03-02

C-reactive protein/albumin ratio (CAR) was originally used as a novel inflammation-based prognostic score in predicting outcomes in septic patients. Recently, more and more studies have reported the prognostic value of pretreatment CAR in solid tumors. However, the results remain controversial rather than conclusive. We conducted a meta-analysis based on 24 studies with 10203 patients to explore the relationship between CAR and survival outcomes in patients with solid tumors. The correlation between CAR and clinicopathological parameters was also assessed. Hazard ratio (HR) or odds ratio (OR) with its 95% confidence interval (CI) was applied to be the effect size estimate. The overall results showed that elevated CAR was associated with shorter overall survival (OS) (including 23 studies and 10067 patients) and poorer disease-free survival (DFS) (including 6 studies and 2904 patients). Significant associations between high CAR level and poor OS were also found in the subgroup analyses of study region, cancer type, primary treatment, clinical stage, cut-off selection, sample size, and cut-off value. Moreover, subgroup analyses demonstrated that study region, primary treatment, clinical stage, sample size, and cut-off value did not alter the prognostic value of CAR for DFS. Furthermore, elevated CAR was correlated with certain phenotypes of tumor aggressiveness, such as poor histological grade, serious clinical stage, advanced tumor depth, positive lymph node metastasis, and positive distant metastasis. Together, our meta-analysis suggests that elevated level of serum CAR predicts worse survival and unfavorable clinical characteristics in cancer patients, and CAR may serve as an effective prognostic factor for solid tumors.

Prognostic value of FDG-PET indices for the assessment of histological response to neoadjuvant chemotherapy and outcome in pediatric patients with Ewing sarcoma and osteosarcoma

PubMed Central

Bailly, Clement; Leforestier, Rodolphe; Campion, Loic; Thebaud, Estelle; Moreau, Anne; Kraeber-Bodere, Francoise

2017-01-01

Purpose The objective of this retrospective work was to evaluate the prognostic value on histological response and survival of quantitative indices derived from FDG-PET performed before and after chemotherapy (CHT), in a homogeneous pediatric Ewing sarcoma (EWS) and Osteosarcoma (OST) population. Methods Thirty-one patients with EWS and 31 with OST were included. All patients were treated with neoadjuvant CHT, and underwent surgery for local control. All patients had FDG-PET at diagnosis and after CHT, prior to surgery. Several parameters were evaluated: SUVmax, SUVpeak, SUVmean, metabolic tumor volume, total lesion glycolysis, 7 textural features and 3 shape features (SF). The segmentation was performed using an adaptive approach. Results were compared to histopathological regression of the resected tumor and to clinical follow-up for survival evaluation. Results For EWS, univariate analysis did not highlight any prognostic value on histological response, or survival regardless of all the considered metrics. For OST, only one of the SF, namely elongation, was significantly associated with PFS and OS on both univariate and multivariate analysis (PFS: p = 0.019, HR = 5.583; OS: p = 0.0062, HR = 7.113). Conclusion Only elongation determined on initial FDG-PET has a potential interest as a prognostic factor of PFS and OS in pediatric OST patients. Unlike recent studies of the literature realized in adult population, all the metrics reveal limited additional prognostic value in pediatric EWS patients. This seems to reinforce the question of whether children experience different subtypes of the same pathologies than older patients, with different outcomes. PMID:28841702

Value of the prognostic nutritional index in advanced gastric cancer treated with preoperative chemotherapy.

PubMed

Sun, Jianyi; Wang, Donghai; Mei, Ying; Jin, Hailong; Zhu, Kankai; Liu, Xiaosun; Zhang, Qing; Yu, Jiren

2017-03-01

The prognostic nutritional index (PNI) is a useful parameter indicating the immune and nutritional status of cancer patients; this study investigated the prognostic value of the PNI in advanced gastric cancer patients treated with preoperative chemotherapy. We retrospectively reviewed 117 advanced gastric cancer patients who met the inclusion criteria for preoperative chemotherapy and underwent surgical resection from July 2004 to December 2011. The patients were divided into PNI-high (PNI ≥ 45) and PNI-low (PNI < 45) groups. Clinicopathologic features, chemotherapy adverse events, and surgical complications were compared between the prechemotherapy PNI-high and PNI-low groups using the chi-square test. Survival analysis was performed using the Kaplan-Meier method and log-rank test. The Cox proportional hazard model was used to identify prognostic factors. Overall survival was better in the prechemotherapy PNI-high group than in the PNI-low group (hazard ratio [HR] = 2.237, 95% confidence interval [CI]: 1.271-3.393, P = 0.005), while there was no significant difference in Overall survival between the postchemotherapy PNI-high and PNI-low groups (P > 0.05). Cox regression analysis indicated that yield pathologic T (ypT), yield pathologic N (ypN) stage, and prechemotherapy PNI were independent prognostic factors (ypT: HR = 2.914, 95% CI = 1.312-6.470, P = 0.009; ypN: HR = 4.909, 95% CI = 1.764-13.660, P = 0.003; prechemotherapy PNI: HR = 1.963, 95% CI = 1.101-3.499, P = 0.022). The prechemotherapy PNI is a useful predictor of the long-term outcome of patients with advanced gastric cancer treated with preoperative chemotherapy. Copyright © 2016 Elsevier Inc. All rights reserved.

Prognostic nomogram and score to predict overall survival in locally advanced untreated pancreatic cancer (PROLAP)

PubMed Central

Vernerey, Dewi; Huguet, Florence; Vienot, Angélique; Goldstein, David; Paget-Bailly, Sophie; Van Laethem, Jean-Luc; Glimelius, Bengt; Artru, Pascal; Moore, Malcolm J; André, Thierry; Mineur, Laurent; Chibaudel, Benoist; Benetkiewicz, Magdalena; Louvet, Christophe; Hammel, Pascal; Bonnetain, Franck

2016-01-01

Background: The management of locally advanced pancreatic cancer (LAPC) patients remains controversial. Better discrimination for overall survival (OS) at diagnosis is needed. We address this issue by developing and validating a prognostic nomogram and a score for OS in LAPC (PROLAP). Methods: Analyses were derived from 442 LAPC patients enrolled in the LAP07 trial. The prognostic ability of 30 baseline parameters was evaluated using univariate and multivariate Cox regression analyses. Performance assessment and internal validation of the final model were done with Harrell's C-index, calibration plot and bootstrap sample procedures. On the basis of the final model, a prognostic nomogram and a score were developed, and externally validated in 106 consecutive LAPC patients treated in Besançon Hospital, France. Results: Age, pain, tumour size, albumin and CA 19-9 were independent prognostic factors for OS. The final model had good calibration, acceptable discrimination (C-index=0.60) and robust internal validity. The PROLAP score has the potential to delineate three different prognosis groups with median OS of 15.4, 11.7 and 8.5 months (log-rank P<0.0001). The score ability to discriminate OS was externally confirmed in 63 (59%) patients with complete clinical data derived from a data set of 106 consecutive LAPC patients; median OS of 18.3, 14.1 and 7.6 months for the three groups (log-rank P<0.0001). Conclusions: The PROLAP nomogram and score can accurately predict OS before initiation of induction chemotherapy in LAPC-untreated patients. They may help to optimise clinical trials design and might offer the opportunity to define risk-adapted strategies for LAPC management in the future. PMID:27404456

The prognostic value of long noncoding RNA Sox2ot expression in various cancers: A systematic review and meta-analysis.

PubMed

Song, Xiaoyang; Yao, Hongyan; Liu, Jinlin; Wang, Qiang

2018-05-19

Several investigations have explored the prognostic value of long noncoding RNA Sox2 overlapping transcript (lncRNA Sox2ot) expression in human cancers, however, with inconsistent results. The aim of this study was to evaluate the prognostic role of lncRNA Sox2ot expression in various cancers. PubMed, Web of Science, Embase, and Cochrane Library were comprehensively searched to retrieve relevant studies. The relationships between lncRNA Sox2ot expression and prognostic parameters were detected, including overall survival (OS), tumor differentiation, clinical stage, distant metastasis, lymph node metastasis and so on. A total of 10 studies involving 943 cancer patients were finally included into the study. High lncRNA Sox2ot expression was significantly related to shorter OS in cancers (HR = 2.06, 95%CI = 1.67-2.55, P < 0.01). The cancer patients with high lncRNA Sox2ot expression tended to have worse tumor differentiation (P = 0.04), advanced clinical stage (P < 0.01), earlier distant metastasis (P < 0.01), and earlier lymph node metastasis (P = 0.01) compared to those with low lncRNA Sox2ot expression. However, there was no distinct correlation between lncRNA Sox2ot expression and age (P = 0.87), gender (P = 0.48), tumor size (P = 0.08), or vascular invasion (P = 0.07). High lncRNA Sox2ot expression was significantly associated with worse OS, advanced clinical stage, worse tumor differentiation, earlier distant metastasis, and earlier lymph node metastasis in various cancers. LncRNA Sox2ot expression might a promising prognostic factor in various cancers. Copyright © 2018 Elsevier B.V. All rights reserved.

A Physics-Based Modeling Framework for Prognostic Studies

NASA Technical Reports Server (NTRS)

Kulkarni, Chetan S.

2014-01-01

Prognostics and Health Management (PHM) methodologies have emerged as one of the key enablers for achieving efficient system level maintenance as part of a busy operations schedule, and lowering overall life cycle costs. PHM is also emerging as a high-priority issue in critical applications, where the focus is on conducting fundamental research in the field of integrated systems health management. The term diagnostics relates to the ability to detect and isolate faults or failures in a system. Prognostics on the other hand is the process of predicting health condition and remaining useful life based on current state, previous conditions and future operating conditions. PHM methods combine sensing, data collection, interpretation of environmental, operational, and performance related parameters to indicate systems health under its actual application conditions. The development of prognostics methodologies for the electronics field has become more important as more electrical systems are being used to replace traditional systems in several applications in the aeronautics, maritime, and automotive fields. The development of prognostics methods for electronics presents several challenges due to the great variety of components used in a system, a continuous development of new electronics technologies, and a general lack of understanding of how electronics fail. Similarly with electric unmanned aerial vehicles, electrichybrid cars, and commercial passenger aircraft, we are witnessing a drastic increase in the usage of batteries to power vehicles. However, for battery-powered vehicles to operate at maximum efficiency and reliability, it becomes crucial to both monitor battery health and performance and to predict end of discharge (EOD) and end of useful life (EOL) events. We develop an electrochemistry-based model of Li-ion batteries that capture the significant electrochemical processes, are computationally efficient, capture the effects of aging, and are of suitable accuracy for reliable EOD prediction in a variety of usage profiles.

Satellite observations of the onset and growth of severe local storms

NASA Technical Reports Server (NTRS)

Negri, A. J.; Vonderhaar, T. H.

1977-01-01

The mesoscale nature of the forcing and evolution of these storms was investigated, with emphasis on techniques to aid in the early detection of such severe events. In the pre-storm environment (t-4 to t-2 hours), the satellite wind fields were combined with moisture parameters to derive horizontal moisture flux information. Low level moisture convergence was indicative of regions of subsequent severe storm genesis. Dynamic parameters such as boundary layer vorticity production and relative vorticity were also useful prognosticators of subsequent severe activity.

Genetic data: The new challenge of personalized medicine, insights for rheumatoid arthritis patients.

PubMed

Goulielmos, George N; Zervou, Maria I; Myrthianou, Effie; Burska, Agata; Niewold, Timothy B; Ponchel, Frederique

2016-06-01

Rapid advances in genotyping technology, analytical methods, and the establishment of large cohorts for population genetic studies have resulted in a large new body of information about the genetic basis of human rheumatoid arthritis (RA). Improved understanding of the root pathogenesis of the disease holds the promise of improved diagnostic and prognostic tools based upon this information. In this review, we summarize the nature of new genetic findings in human RA, including susceptibility loci and gene-gene and gene-environment interactions, as well as genetic loci associated with sub-groups of patients and those associated with response to therapy. Possible uses of these data are discussed, such as prediction of disease risk as well as personalized therapy and prediction of therapeutic response and risk of adverse events. While these applications are largely not refined to the point of clinical utility in RA, it seems likely that multi-parameter datasets including genetic, clinical, and biomarker data will be employed in the future care of RA patients. Copyright © 2016 Elsevier B.V. All rights reserved.

Imaging intratumor heterogeneity: role in therapy response, resistance, and clinical outcome.

PubMed

O'Connor, James P B; Rose, Chris J; Waterton, John C; Carano, Richard A D; Parker, Geoff J M; Jackson, Alan

2015-01-15

Tumors exhibit genomic and phenotypic heterogeneity, which has prognostic significance and may influence response to therapy. Imaging can quantify the spatial variation in architecture and function of individual tumors through quantifying basic biophysical parameters such as CT density or MRI signal relaxation rate; through measurements of blood flow, hypoxia, metabolism, cell death, and other phenotypic features; and through mapping the spatial distribution of biochemical pathways and cell signaling networks using PET, MRI, and other emerging molecular imaging techniques. These methods can establish whether one tumor is more or less heterogeneous than another and can identify subregions with differing biology. In this article, we review the image analysis methods currently used to quantify spatial heterogeneity within tumors. We discuss how analysis of intratumor heterogeneity can provide benefit over more simple biomarkers such as tumor size and average function. We consider how imaging methods can be integrated with genomic and pathology data, instead of being developed in isolation. Finally, we identify the challenges that must be overcome before measurements of intratumoral heterogeneity can be used routinely to guide patient care. ©2014 American Association for Cancer Research.

Relationship Between Physiological Parameters and Acute Coronary Syndrome in Patients Presenting to the Emergency Department With Undifferentiated Chest Pain.

PubMed

Greenslade, Jaimi H; Beamish, Daniel; Parsonage, William; Hawkins, Tracey; Schluter, Jessica; Dalton, Emily; Parker, Kate; Than, Martin; Hammett, Christopher; Lamanna, Arvin; Cullen, Louise

2016-01-01

The investigators of this study sought to examine whether abnormal physiological parameters are associated with increased risk for acute coronary syndrome (ACS) in patients presenting to the emergency department (ED) with chest pain. We used prospectively collected data on adult patients presenting with suspected ACS in 2 EDs in Australia and New Zealand. Trained research nurses collected physiological data including temperature, respiratory rate, heart rate, and systolic blood pressure (SBP) on presentation to the ED. The primary endpoint was ACS within 30 days of presentation, as adjudicated by cardiologists using standardized guidelines. The prognostic utility of physiological parameters for ACS was examined using risk ratios. Acute coronary syndrome was diagnosed in 384 of the 1951 patients (20%) recruited. Compared with patients whose SBP was between 100 and 140 mm Hg, patients with an SBP of lower than 100 mm Hg or higher than 140 mm Hg were 1.4 times (95% confidence interval, 1.2-1.7) more likely to have ACS. Similarly, compared with patients whose temperature was between 36.5°C and 37.5°C, patients with temperature of lower than 36.5°C or higher than 37.5°C were 1.4 times (95% confidence interval, 1.1-1.6) more likely to have ACS. Heart rate and respiratory rate were not predictors of ACS. Patients with abnormal temperature or SBP were slightly more likely to have ACS, but such risk was of too small a magnitude to be useful in clinical decision making. Other physiological parameters (heart rate and respiratory rate) had no prognostic value. The use of physiological parameters cannot reliably confirm or rule out ACS.

[THE COMPARISON OF RESULTS OF DETECTION OF MINIMAL RESIDUAL DISEASE IN PERIPHERAL BLOOD AND MARROW IN CHILDREN OF THE FIRST YEAR OF LIFE WITH ACUTE LYMPHOBLASTIC LEUCOSIS].

PubMed

Tsaur, G A; Riger, T O; Popov, A M; Nasedkina, T V; Kustanovich, A M; Solodovnikov, A G; Streneva, O V; Shorikov, E V; Tsvirenko, S V; Saveliev, L I; Fechina, L G

2015-04-01

The occurrence of minimal residual disease is an important prognostic factor under acute lymphoblastic leucosis in children and adults. In overwhelming majority of research studies bone marrow is used to detect minimal residual disease. The comparative characteristic of detection of minimal residual disease in peripheral blood and bone marrow was carried out. The prognostic role of occurrence of minimal residual disease in peripheral blood and bone marrow under therapy according protocol MLL-Baby was evaluated. The analysis embraced 142 pair samples from 53 patients with acute lymphoblastic leucosis and various displacements of gene MLL younger than 365 days. The minimal residual disease was detected by force of identification of chimeric transcripts using polymerase chain reaction in real-time mode in 7 sequential points of observation established by protocol of therapy. The comparability of results of qualitative detection of minimal residual disease in bone marrow and peripheral blood amounted to 84.5%. At that, in all 22 (15.5%) discordant samples minimal residual disease was detected only in bone marrow. Despite of high level of comparability of results of detection of minimal residual disease in peripheral blood and bone marrow the occurrence of minimal residual disease in peripheral blood at various stages of therapy demonstrated no independent prognostic significance. The established differences had no relationship with sensitivity of method determined by value of absolute expression of gene ABL. Most likely, these differences reflected real distribution of tumor cells. The results of study demonstrated that application of peripheral blood instead of bone marrow for monitoring of minimal residual disease under acute lymphoblastic leucosis in children of first year of life is inappropriate. At the same time, retention of minimal residual disease in TH4 in bone marrow was an independent and prognostic unfavorable factor under therapy of acute lymphoblastic leucosis of children of first year of life according protocol MLL-Baby (OO=7.326, confidence interval 2.378-22.565).

New and emerging prognostic and predictive genetic biomarkers in B-cell precursor acute lymphoblastic leukemia

PubMed Central

Moorman, Anthony V.

2016-01-01

Acute lymphoblastic leukemia (ALL) is a heterogeneous disease at the genetic level. Chromosomal abnormalities are used as diagnostic, prognostic and predictive biomarkers to provide subtype, outcome and drug response information. t(12;21)/ETV6-RUNX1 and high hyper-diploidy are good-risk prognostic biomarkers whereas KMT2A (MLL) translocations, t(17;19)/TCF3-HLF, haploidy or low hypodiploidy are high-risk biomarkers. t(9;22)/BCR-ABL1 patients require targeted treatment (imatinib/dasatinib), whereas iAMP21 patients achieve better outcomes when treated intensively. High-risk genetic biomarkers are four times more prevalent in adults compared to children. The application of genomic technologies to cases without an established abnormality (B-other) reveals copy number alterations which can be used either individually or in combination as prognostic biomarkers. Transcriptome sequencing studies have identified a network of fusion genes involving kinase genes - ABL1, ABL2, PDGFRB, CSF1R, CRLF2, JAK2 and EPOR. In vitro and in vivo studies along with emerging clinical observations indicate that patients with a kinase-activating aberration may respond to treatment with small molecular inhibitors like imatinib/dasatinib and ruxolitinib. Further work is required to determine the true frequency of these abnormalities across the age spectrum and the optimal way to incorporate such inhibitors into protocols. In conclusion, genetic biomarkers are playing an increasingly important role in the management of patients with ALL. PMID:27033238

Development and External Validation of a Prognostic Nomogram for Metastatic Uveal Melanoma

PubMed Central

Valpione, Sara; Moser, Justin C.; Parrozzani, Raffaele; Bazzi, Marco; Mansfield, Aaron S.; Mocellin, Simone; Pigozzo, Jacopo; Midena, Edoardo; Markovic, Svetomir N.; Aliberti, Camillo; Campana, Luca G.; Chiarion-Sileni, Vanna

2015-01-01

Background Approximately 50% of patients with uveal melanoma (UM) will develop metastatic disease, usually involving the liver. The outcome of metastatic UM (mUM) is generally poor and no standard therapy has been established. Additionally, clinicians lack a validated prognostic tool to evaluate these patients. The aim of this work was to develop a reliable prognostic nomogram for clinicians. Patients and Methods Two cohorts of mUM patients, from Veneto Oncology Institute (IOV) (N=152) and Mayo Clinic (MC) (N=102), were analyzed to develop and externally validate, a prognostic nomogram. Results The median survival of mUM was 17.2 months in the IOV cohort and 19.7 in the MC cohort. Percentage of liver involvement (HR 1.6), elevated levels of serum LDH (HR 1.6), and a WHO performance status=1 (HR 1.5) or 2–3 (HR 4.6) were associated with worse prognosis. Longer disease-free interval from diagnosis of UM to that of mUM conferred a survival advantage (HR 0.9). The nomogram had a concordance probability of 0.75 (SE .006) in the development dataset (IOV), and 0.80 (SE .009) in the external validation (MC). Nomogram predictions were well calibrated. Conclusions The nomogram, which includes percentage of liver involvement, LDH levels, WHO performance status and disease free-interval accurately predicts the prognosis of mUM and could be useful for decision-making and risk stratification for clinical trials. PMID:25780931

High anaplastic lymphoma kinase immunohistochemical staining in neuroblastoma and ganglioneuroblastoma is an independent predictor of poor outcome.

PubMed

Duijkers, Floor A M; Gaal, José; Meijerink, Jules P P; Admiraal, Pieter; Pieters, Rob; de Krijger, Ronald R; van Noesel, Max M

2012-03-01

Anaplastic lymphoma kinase (ALK) mutations occur in 3% to 11% of neuroblastoma (NBL) cases and are associated with high ALK levels. However, high ALK levels appear to be a mutation-independent hallmark of NBL. Evidence about the prognostic relevance of ALK mutations and ALK tumor positivity in patients with NBL has been inconclusive. In this study, we investigated the prognostic relevance of ALK positivity by IHC and ALK mutation status by PCR sequencing in 71 NBL, 12 ganglioneuroblastoma (GNBL), and 20 ganglioneuroma samples in a multivariate model. ALK mutations were present in 2 of 72 NBL and 2 of 12 GNBL samples, which all contained many ALK-positive cells (>50%). In addition, half of all NBL samples showed ALK positivity in most (>50%) of tumor cells, whereas half of the GNBL showed staining in <20% of the tumor cells. In most ganglioneuroma samples, a low percentage of tumor cells stained positive for ALK, which mainly involved ganglion cells. Higher percentages of ALK-positive cells in NBL and GNBL patient samples correlated with inferior survival in univariate and multivariate analyses with established prognostic factors, such as stage, age, and MYCN status. In conclusion, ALK positivity by IHC is an independent, poor prognostic factor in patients with GNBL and NBL. ALK IHC is an easy test suitable for future risk stratification in patients with NBL and GNBL. Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Clinicopathological significance and prognostic role of p-STAT3 in patients with hepatocellular carcinoma.

PubMed

Liang, Chaojie; Xu, Yingchen; Ge, Hua; Li, Guangming; Wu, Jixiang

2018-01-01

Constitutive activation of STAT3 through its phosphorylation (p-STAT3) plays a key role in the development and progression of various cancers. However, the relationship between p-STAT3 expression and the clinicopathological features and prognostic value in patients with hepatocellular carcinoma (HCC) remains controversial. We conducted a meta-analysis to evaluate the role of p-STAT3 in HCC. The PubMed, Cochrane Library, Web of Science, EMBASE, Chinese CNKI, and Chinese Wanfang databases were searched using the appropriate terms to find the relevant studies on p-STAT3 and HCC. The relationship between p-STAT3 expression and clinicopathological characteristics and prognostic value was established. Pool odds ratios (ORs) and hazard ratios (HRs) with 95% CIs were calculated using the STATA 14.2 software. The eight articles included in this meta-analysis comprised 752 patients. Expression of p-STAT3 was associated with incidence, age, liver cirrhosis, tumor size, vascular invasion, and TNM stage of HCC, but it was not related to gender, alpha-fetoprotein (AFP), hepatitis B surface antigen (HBsAg), number of tumors, and tumor differentiation. Additionally, the expression of p-STAT3 was related to a poor 3- and 5-year overall survival rate and disease-free survival rate. Expression of p-STAT3 was associated with the incidence, age, liver cirrhosis, tumor size, vascular invasion, and TNM stage. Thus, p-STAT3 can be a reliable prognostic biomarker for HCC. Further high-quality studies with larger numbers of patients are needed.

Long leukocyte telomere length in prostate cancer patients at diagnosis is associated with poor metastasis-free and cancer-specific survival.

PubMed

Svenson, Ulrika; Roos, Göran; Wikström, Pernilla

2017-02-01

Previous studies have suggested that leukocyte telomere length is associated with risk of developing prostate cancer. Investigations of leukocyte telomere length as a prognostic factor in prostate cancer are, however, lacking. In this study, leukocyte telomere length was investigated both as a risk marker, comparing control subjects and patient risk groups (based on serum levels of prostate-specific antigen, tumor differentiation, and tumor stage), and as a prognostic marker for metastasis-free and cancer-specific survival. Relative telomere length was measured by a well-established quantitative polymerase chain reaction method in 415 consecutively sampled individuals. Statistical evaluation included 162 control subjects without cancer development during follow-up and 110 untreated patients with newly diagnosed localized prostate cancer at the time of blood draw. Leukocyte telomere length did not differ significantly between control subjects and patients, or between patient risk groups. Interestingly, however, and in line with our previous results in breast and kidney cancer patients, relative telomere length at diagnosis was an independent prognostic factor. Patients with long leukocyte telomeres (⩾median) had a significantly worse prostate cancer-specific and metastasis-free survival compared to patients with short telomere length. In contrast, for patients who died of other causes than prostate cancer, long relative telomere length was not coupled to shorter survival time. To our knowledge, these results are novel and give further strength to our hypothesis that leukocyte telomere length might be used as a prognostic marker in malignancy.

The Effect of Self-Reported and Performance-Based Functional Impairment on Future Hospital Costs of Community-Dwelling Older Persons

ERIC Educational Resources Information Center

Reuben, David B.; Seeman, Teresa E.; Keeler, Emmett; Hayes, Risa P.; Bowman, Lee; Sewall, Ase; Hirsch, Susan H.; Wallace, Robert B.; Guralnik, Jack M.

2004-01-01

Purpose: We determined the prognostic value of self-reported and performance-based measurement of function, including functional transitions and combining different measurement approaches, on utilization. Design and Methods: Our cohort study used the 6th, 7th, and 10th waves of three sites of the Established Populations for Epidemiologic Studies…

Data Mining for Anomaly Detection

NASA Technical Reports Server (NTRS)

Biswas, Gautam; Mack, Daniel; Mylaraswamy, Dinkar; Bharadwaj, Raj

2013-01-01

The Vehicle Integrated Prognostics Reasoner (VIPR) program describes methods for enhanced diagnostics as well as a prognostic extension to current state of art Aircraft Diagnostic and Maintenance System (ADMS). VIPR introduced a new anomaly detection function for discovering previously undetected and undocumented situations, where there are clear deviations from nominal behavior. Once a baseline (nominal model of operations) is established, the detection and analysis is split between on-aircraft outlier generation and off-aircraft expert analysis to characterize and classify events that may not have been anticipated by individual system providers. Offline expert analysis is supported by data curation and data mining algorithms that can be applied in the contexts of supervised learning methods and unsupervised learning. In this report, we discuss efficient methods to implement the Kolmogorov complexity measure using compression algorithms, and run a systematic empirical analysis to determine the best compression measure. Our experiments established that the combination of the DZIP compression algorithm and CiDM distance measure provides the best results for capturing relevant properties of time series data encountered in aircraft operations. This combination was used as the basis for developing an unsupervised learning algorithm to define "nominal" flight segments using historical flight segments.

[Consensus statement on biomarkers in breast cancer by the Spanish Society of Pathology and the Spanish Society of Medical Oncology].

PubMed

Palacios Calvo, José; Albanell, Joan; Rojo, Federico; Ciruelos, Eva; Aranda-López, Ignacio; Cortés, Javier; García-Caballero, Tomás; Martín, Miguel; López-García, María Ángeles; Colomer, Ramon

This consensus statement is a joint initiative of the Spanish Society of Pathology (SEAP) and the Spanish Society of Medical Oncology (SEOM). It revises and updates the recommendations for the use of biomarkers in the diagnosis and treatment of breast cancer. The group of experts recommends that, in all cases of breast cancer, the histologic grade and the alpha-estrogen receptor (ER), progesterone receptor, Ki-67 and HER2 status should be determined, in order to assist prognosis and establish therapeutic options, including hormone therapy, chemotherapy and anti-HER2 therapy. One of the four available genetic prognostic platforms (MammaPrint ® , Oncotype DX ® , Prosigna ® or EndoPredict ® ) may be used in node-negative ER-positive patients to establish a prognostic category and decide, together with the patient, whether adjuvant treatment be limited to hormonal therapy. Newer technologies, including next generation sequencing, liquid biopsy, tumour infiltrating lymphocytes or PD-1 determination, are still investigational. Copyright © 2018 Sociedad Española de Anatomía Patológica. Publicado por Elsevier España, S.L.U. All rights reserved.

Contrasting breast cancer molecular subtypes across serial tumor progression stages: biological and prognostic implications

PubMed Central

Kimbung, Siker; Kovács, Anikó; Danielsson, Anna; Bendahl, Pär-Ola; Lövgren, Kristina; Stolt, Marianne Frostvik; Tobin, Nicholas P.; Lindström, Linda; Bergh, Jonas; Einbeigi, Zakaria; Fernö, Mårten; Hatschek, Thomas; Hedenfalk, Ingrid

2015-01-01

The relevance of the intrinsic subtypes for clinical management of metastatic breast cancer is not comprehensively established. We aimed to evaluate the prevalence and prognostic significance of drifts in tumor molecular subtypes during breast cancer progression. A well-annotated cohort of 304 women with advanced breast cancer was studied. Tissue microarrays of primary tumors and synchronous lymph node metastases were constructed. Conventional biomarkers were centrally assessed and molecular subtypes were assigned following the 2013 St Gallen guidelines. Fine-needle aspirates of asynchronous metastases were transcriptionally profiled and subtyped using PAM50. Discordant expression of individual biomarkers and molecular subtypes was observed during tumor progression. Primary luminal-like tumors were relatively unstable, frequently adopting a more aggressive subtype in the metastases. Notably, loss of ER expression and a luminal to non-luminal subtype conversion was associated with an inferior post-recurrence survival. In addition, ER and molecular subtype assessed at all tumor progression stages were independent prognostic factors for post-recurrence breast cancer mortality in multivariable analyses. Our results demonstrate that drifts in tumor molecular subtypes may occur during tumor progression, conferring adverse consequences on outcome following breast cancer relapse. PMID:26375671

Two microRNA signatures for malignancy and immune infiltration predict overall survival in advanced epithelial ovarian cancer.

PubMed

Korsunsky, Ilya; Parameswaran, Janaki; Shapira, Iuliana; Lovecchio, John; Menzin, Andrew; Whyte, Jill; Dos Santos, Lisa; Liang, Sharon; Bhuiya, Tawfiqul; Keogh, Mary; Khalili, Houman; Pond, Cassandra; Liew, Anthony; Shih, Andrew; Gregersen, Peter K; Lee, Annette T

2017-10-01

MicroRNAs have been established as key regulators of tumor gene expression and as prime biomarker candidates for clinical phenotypes in epithelial ovarian cancer (EOC). We analyzed the coexpression and regulatory structure of microRNAs and their co-localized gene targets in primary tumor tissue of 20 patients with advanced EOC in order to construct a regulatory signature for clinical prognosis. We performed an integrative analysis to identify two prognostic microRNA/mRNA coexpression modules, each enriched for consistent biological functions. One module, enriched for malignancy-related functions, was found to be upregulated in malignant versus benign samples. The second module, enriched for immune-related functions, was strongly correlated with imputed intratumoral immune infiltrates of T cells, natural killer cells, cytotoxic lymphocytes, and macrophages. We validated the prognostic relevance of the immunological module microRNAs in the publicly available The Cancer Genome Atlas data set. These findings provide novel functional roles for microRNAs in the progression of advanced EOC and possible prognostic signatures for survival. © American Federation for Medical Research (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Heterogeneous impact of alcohol consumption according to treatment method on survival in head and neck cancer: A prospective study.

PubMed

Sawabe, Michi; Ito, Hidemi; Oze, Isao; Hosono, Satoyo; Kawakita, Daisuke; Tanaka, Hideo; Hasegawa, Yasuhisa; Murakami, Shingo; Matsuo, Keitaro

2017-01-01

Alcohol consumption is an established risk factor, and also a potential prognostic factor, for squamous cell carcinoma of the head and neck (HNSCC). However, little is known about whether the prognostic impact of alcohol consumption differs by treatment method. We evaluated the association between alcohol drinking and survival by treatment method to the primary site in 427 patients with HNSCC treated between 2005 and 2013 at Aichi Cancer Center Central Hospital (Nagoya, Japan). The impact of alcohol on prognosis was measured by multivariable Cox regression analysis adjusted for established prognostic factors. Among all HNSCC patients, the overall survival rate was significantly poorer with increased levels of alcohol consumption in multivariable analysis (trend P = 0.038). Stratification by treatment method and primary site revealed that the impact of drinking was heterogeneous. Among laryngopharyngeal cancer (laryngeal, oropharyngeal, and hypopharyngeal cancer) patients receiving radiotherapy (n = 141), a significant dose-response relationship was observed (trend P = 0.034). In contrast, among laryngopharyngeal cancer patients treated with surgery (n = 80), no obvious impact of alcohol was observed. This heterogeneity in the impact of alcohol between surgery and radiotherapy was significant (for interaction, P = 0.048). Furthermore, among patients with oral cavity cancer treated by surgery, a significant impact of drinking on survival was seen with tongue cancer, but not with non-tongue oral cancer. We observed a significant inverse association between alcohol drinking and prognosis among HNSCC patients, and its impact was heterogeneous by treatment method and primary site. © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Prognosticators and risk grouping in patients with lung metastasis from nasopharyngeal carcinoma: a more accurate and appropriate assessment of prognosis.

PubMed

Cao, Xun; Luo, Rong-Zhen; He, Li-Ru; Li, Yong; Lin, Wen-Qian; Chen, You-Fang; Wen, Zhe-Sheng

2011-08-26

Lung metastases arising from nasopharyngeal carcinomas (NPC) have a relatively favourable prognosis. The purpose of this study was to identify the prognostic factors and to establish a risk grouping in patients with lung metastases from NPC. A total of 198 patients who developed lung metastases from NPC after primary therapy were retrospectively recruited from January 1982 to December 2000. Univariate and multivariate analyses of clinical variables were performed using Cox proportional hazards regression models. Actuarial survival rates were plotted against time using the Kaplan-Meier method, and log-rank testing was used to compare the differences between the curves. The median overall survival (OS) period and the lung metastasis survival (LMS) period were 51.5 and 20.9 months, respectively. After univariate and multivariate analyses of the clinical variables, age, T classification, N classification, site of metastases, secondary metastases and disease-free interval (DFI) correlated with OS, whereas age, VCA-IgA titre, number of metastases and secondary metastases were related to LMS. The prognoses of the low- (score 0-1), intermediate- (score 2-3) and high-risk (score 4-8) subsets based on these factors were significantly different. The 3-, 5- and 10-year survival rates of the low-, intermediate- and high-risk subsets, respectively (P < 0.001) were as follows: 77.3%, 60% and 59%; 52.3%, 30% and 27.8%; and 20.5%, 7% and 0%. In this study, clinical variables provided prognostic indicators of survival in NPC patients with lung metastases. Risk subsets would help in a more accurate assessment of a patient's prognosis in the clinical setting and could facilitate the establishment of patient-tailored medical strategies and supports.

Ratio of progesterone-to-number of follicles as a prognostic tool for in vitro fertilization cycles.

PubMed

Roque, Matheus; Valle, Marcello; Sampaio, Marcos; Geber, Selmo; Checa, Miguel Angel

2015-06-01

To establish a ratio of the P level to the number of follicles (P/F ratio) on the day of human chorionic gonadotropin (hCG) administration and to evaluate whether this ratio is associated with in vitro fertilization (IVF) outcome. This study was conducted between January 2012 and June 2013. A total of 337 patients with cleavage-stage day-3 fresh embryo transfer with P levels ≤1.5 ng/mL on the day of hCG administration were included in the study. The main outcome was ongoing pregnancy rate. The P/F ratio was calculated according to the equation (P[ng/mL]/number of follicles) on the day of final oocyte maturation. Using ROC, we established a cut-off level of 0.075 for the P/F ratio. The area under the curve (AUC) (0.756; 95 % confidence interval [CI]: 0.704-0.807) indicated that it was a good prognostic test. In group 1 (patients under 36 years old), the ongoing pregnancy rates were 57 and 30 % for patients with P/F ratios ≤ .075 and > .075, respectively, (p = 0.003). In group 2 (patients between 36 and 39 years old), the ongoing pregnancy rates were 58 % and 17 % (p = 0.001) for patients with P/F ratios ≤ .075 and > .075, respectively. In group 3 (patients ≥ 40 years old), the ongoing pregnancy rates were 41.7 and 10.9 % (p = 0.001) for patients with P/F ratios ≤ .075 and > .075, respectively. The P/F ratio is a good prognostic test for predicting IVF outcome that can correlate the P level with ovarian response.

Plasma suPAR as a prognostic biological marker for ICU mortality in ARDS patients.

PubMed

Geboers, Diederik G P J; de Beer, Friso M; Tuip-de Boer, Anita M; van der Poll, Tom; Horn, Janneke; Cremer, Olaf L; Bonten, Marc J M; Ong, David S Y; Schultz, Marcus J; Bos, Lieuwe D J

2015-07-01

We investigated the prognostic value of plasma soluble urokinase plasminogen activator receptor (suPAR) on day 1 in patients with the acute respiratory distress syndrome (ARDS) for intensive care unit (ICU) mortality and compared it with established disease severity scores on day 1. suPAR was determined batchwise in plasma obtained within 24 h after admission. 632 ARDS patients were included. Significantly (P = 0.02) higher median levels of suPAR were found with increasing severity of ARDS: 5.9 ng/ml [IQR 3.1-12.8] in mild ARDS (n = 82), 8.4 ng/ml [IQR 4.1-15.0] in moderate ARDS (n = 333), and 9.0 ng/ml [IQR 4.5-16.0] in severe ARDS (n = 217). Non-survivors had higher median levels of suPAR [12.5 ng/ml (IQR 5.1-19.5) vs. 7.4 ng/ml (3.9-13.6), P < 0.001]. The area under the receiver operator characteristic curve (ROC-AUC) for mortality of suPAR (0.62) was lower than the ROC-AUC of the APACHE IV score (0.72, P = 0.007), higher than that of the ARDS definition classification (0.53, P = 0.005), and did not differ from that of the SOFA score (0.68, P = 0.07) and the oxygenation index (OI) (0.58, P = 0.29). Plasma suPAR did not improve the discrimination of the established disease severity scores, but did improve net reclassification of the APACHE score (29%), SOFA score (23%), OI (38%), and Berlin definition classification (39%). As a single biological marker, the prognostic value for death of plasma suPAR in ARDS patients is low. Plasma suPAR, however, improves the net reclassification, suggesting a potential role for suPAR in ICU mortality prediction models.

Tissue expression of MLH1, PMS2, MSH2, and MSH6 proteins and prognostic value of microsatellite instability in Wilms tumor: experience of 45 cases.

PubMed

Diniz, Gulden; Aktas, Safiye; Cubuk, Cankut; Ortac, Ragip; Vergin, Canan; Olgun, Nur

2013-05-01

Although the importance of microsatellite instability (MSI) and mismatch repair genes (MMR) is strongly established in colorectal cancer seen in the Lynch syndrome, its significance has not been fully established in Wilms tumor (WT). The aim of this study was to determine the prognostic value of MSI and MMR proteins in WT. This study included 45 pediatric cases with nephroblastoma. Protein expression was analyzed by immunohistochemistry of archival tissue sections. Real-time PCR melting analysis and fluorescence capillary electrophoresis (FCE) were performed to evaluate the MSI markers BAT25, BAT26, NR21, NR24, MONO27, penta D, and penta C in DNA extracted from tumor and normal tissues. Lower levels of MSI were observed in six cases (13.3%). There were no statistically significant correlations between MSI and some clinical prognostic factors such as stage of the tumors, and survival rates. Nineteen tumors (42.2%) showed loss of protein expression of MLH1, PMS2, MSH2, or MSH6. MMR protein defects were correlated with size (P = .021), and stage (P = .019) of the tumor, and survival rates (P < .01).Similarly MSI was also correlated with the size of the tumor (P = .046). This study showed that a small proportion of WT might be associated with the presence of MSI, as is the case with defects of DNA mismatch repair genes in the pathogenesis of WT. However, there was no concordance with the frequency of tissue expression of MMR proteins and MSI. These findings suggest that MMR genes may play an important role in the development of WT via different pathways.

Histologic parameters predictive of disease outcome in women with advanced stage ovarian carcinoma treated with neoadjuvant chemotherapy.

PubMed

Samrao, Damanzoopinder; Wang, Dan; Ough, Faith; Lin, Yvonne G; Liu, Song; Menesses, Teodulo; Yessaian, Annie; Turner, Nicole; Pejovic, Tanja; Mhawech-Fauceglia, Paulette

2012-12-01

The use of neoadjuvant chemotherapy followed by tumor reduction surgery, also called interval debulking surgery (IDS), is considered an alternative therapeutic regimen for selected patients with advanced stage epithelial ovarian cancer (EOC). Although minimal residual disease has been proven to be a prognostic factor in traditional cytoreduction for advanced stage EOC, predictive factors after IDS still remain unexplored. The aim of this study was to determine the prognostic value of post-neoadjuvant histologic changes with clinical outcome. Three pathologists evaluated 67 cases for the following parameters: fibrosis, necrosis, residual tumor, and inflammation. The Cohen's kappa statistic was used to measure agreement among pathologists. Univariate and multivariate Cox proportional hazards models were used to determine the association between histologic parameters and recurrence-free survival (RFS) and overall survival (OS). There was substantial to almost perfect agreement among the three pathologists in all four histologic parameters (k ranged from 0.65 to 0.97). Fibrosis was associated with longer RFS (P = 0.0257) with a median of 20 months for tumors with fibrosis (3+) versus 12 months for tumors with fibrosis (1+, 2+) and longer OS (P = 0.0249) with a median of 51 months for tumors with fibrosis (3+) versus 32 months for tumors with fibrosis (1+, 2+). Our results revealed that patients with tumors exhibiting fibrosis (1+, 2+), as well as necrosis (0, 1+), had significant shorter RFS and OS (P = 0.059 and P = 0.0234, respectively). We suggest that the assessment of fibrosis and necrosis should be implemented in pathologic evaluation and prospectively validated in future studies.

Hematologic and biochemical characteristics of stranded green sea turtles.

PubMed

March, Duane T; Vinette-Herrin, Kimberly; Peters, Andrew; Ariel, Ellen; Blyde, David; Hayward, Doug; Christidis, Les; Kelaher, Brendan P

2018-05-01

To improve understanding of pathophysiologic processes occurring in green sea turtles ( Chelonia mydas) stranded along the east coast of Australia, we retrospectively examined the hematologic and biochemical blood parameters of 127 green turtles admitted to 2 rehabilitation facilities, Dolphin Marine Magic (DMM) and Taronga Zoo (TZ), between 2002 and 2016. The predominant size class presented was small immature animals (SIM), comprising 88% and 69% of admissions to DMM and TZ, respectively. Significant differences in blood profiles were noted between facility, size, and outcome. Elevated levels of aspartate aminotransferase (AST) and heterophils were poor prognostic indicators in animals from TZ, but not DMM. SIM animals at both institutions had lower protein levels than large older (LO) animals. SIM animals at DMM also had lower hematocrit and monocyte concentration; SIM animals at TZ had lower heterophil counts. Urea was measured for 27 SIM animals from TZ, but the urea-to-uric acid ratio was not prognostically useful. Strong correlations were seen between AST and glutamate dehydrogenase (GDH; r = 0.68) and uric acid and bile acids ( r = 0.72) in the 45 SIM animals from DMM in which additional analytes were measured. χ 2 contingency tests showed that the most recently published reference intervals were not prognostically useful. A paired t-test showed that protein levels rose and heterophil numbers fell in the 15 SIM animals from TZ during the rehabilitation process. Our results indicate that further work is required to identify reliable prognostic biomarkers for green turtles.

[Clinical and prognostic significance of preoperative serum CA153, CEA and TPS levels in patients with primary breast cancer].

PubMed

Chen, Yan; Zheng, Yu-hong; Lin, Ying-ying; Hu, Min-hua; Chen, Yan-song

2011-11-01

To investigate the clinical and prognostic values of preoperative serum CA153, CEA and TPS levels in patients with primary breast cancer. A total of 386 hospitalized patients with stage I ∼ IV breast cancer from Nov 1998 to Feb 2009 were followed up, and their clinicopathological data were analyzed retrospectively to determine the factors affecting their prognosis. First, preoperative serum CA153 expression level was significantly associated with the age of onset and tumor size (P < 0.05), the expression of serum CEA was correlated with tumor size (P < 0.05), and the expression of serum tissue polypeptide specific antigen (TPS) was correlated with tumor size and lymph node metastases (P < 0.05). Second, the overall survival was significantly shorter among patients with elevated serum CA153, CEA or TPS, respectively (P < 0.05 for overall). Finally, multivariate Cox regression analysis indicated that estrogen receptor status (ER) and elevated preoperative values of CA 153 are independent prognostic factors for overall survival (P < 0.05), and CA 153 is a risk factor but estrogen receptor status is a protective factor for overall survival. Higher preoperative expression of serum CA153, CEA or TPS is closely correlated with clinicopathological characteristics and overall survival. The prognosis is poorer in primary breast cancer patients with higher CA15-3 expression level, and pre-treatment CA153 expression level can be used as an independent prognostic parameter in patients with primarily breast cancer.

Prognostic relevance of epithelial-mesenchymal transition and proliferation in surgically treated primary parotid gland cancer.

PubMed

Busch, Alina; Bauer, Larissa; Wardelmann, Eva; Rudack, Claudia; Grünewald, Inga; Stenner, Markus

2017-05-01

Cancer of the major salivary glands comprises a morphologically diverse group of rare tumours of largely unknown cause. Epithelial-mesenchymal transition (EMT) has been shown to play a significant prognostic role in various human cancers. The aim was to assess the expression of EMT markers in different histological subtypes of parotid gland cancer (PGC) and analyse their prognostic value. We examined 94 PGC samples (13 histological subtypes) for the expression of MIB-1, epithelial cadherin (E-cadherin), β-catenin, vimentin and cytokeratin 8/18 (CK8/18) by means of immunohistochemistry. The experimental findings were correlated with clinicopathological and survival parameters. We detected all analysed EMT and proliferation markers in specifically different constellations within the examined histological subtypes of PGC. We found high epithelial marker expressions (CK8/18, E-cadherin, membranous β-catenin) only in a distinct variety of carcinomas. A high proliferation rate (high MIB-1 expression) as well as a combination of high CK8/18 and low vimentin expression was associated with a significantly worse survival. Our findings indicate that activation of the EMT pathway is a relevant explanation for tumour progression in individual histological subtypes of malignant parotid gland lesions, but by far not in all. Evidence of EMT activation in PGC cannot be seen as an isolated prognostic factor. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Clinicopathological and prognostic significance of MUC4 expression in cancers: evidence from meta-analysis.

PubMed

Huang, Xing; Wang, Xin; Lu, Shi-Ming; Chen, Chen; Wang, Jie; Zheng, Yan-Yan; Ren, Bin-Hui; Xu, Lin

2015-01-01

Mucin4 (MUC4) is a secreted glycoprotein. Numerous studies had indicated that MUC4 was an attractive prognostic tumor biomarker. However, the results of different studies have been inconsistent. So we conducted this meta-analysis to explore the association between MUC4 expression and cancer prognosis. A systematically comprehensive search was performed through PubMed, EMBASE and CNKI (Chinese National Knowledge Infrastructure). Prognostic value of MUC4 expression in malignancy patients was evaluated by pooled hazard ratios (HRs) and their 95% confidence intervals (CIs). Meanwhile, pooled odds ratio (OR) with 95% CI was appropriate for the association between MUC4 expression and clinicopathological parameters. Eighteen studies including 1,933 patients were enrolled in this meta-analysis. Significant association was found between elevated MUC4 expression and poorer overall survival (OS) with pooled hazard ratio (HR) of 1.87 [95% confidence interval (CI): 1.58-2.23, P<0.001]. Significant associations were also detected in biliary tract carcinoma (HR: 2.41, 95% CI: 1.69-3.42, P<0.001), pancreatic cancer (HR: 2.01, 95% CI: 1.42-2.86, P<0.001) and colorectal cancer (HR: 1.73, 95% CI: 1.17-2.54, P=0.006). Moreover, combined odds ratio (OR) of MUC4 indicated that MUC4 overexpression was associated with tumor stage, tumor invasion and lymph node metastasis. Our results demonstrated that MUC4 may be exploited as a novel prognostic biomarker for cancer patients.

Clinicopathological and prognostic significance of MUC4 expression in cancers: evidence from meta-analysis

PubMed Central

Huang, Xing; Wang, Xin; Lu, Shi-Ming; Chen, Chen; Wang, Jie; Zheng, Yan-Yan; Ren, Bin-Hui; Xu, Lin

2015-01-01

Mucin4 (MUC4) is a secreted glycoprotein. Numerous studies had indicated that MUC4 was an attractive prognostic tumor biomarker. However, the results of different studies have been inconsistent. So we conducted this meta-analysis to explore the association between MUC4 expression and cancer prognosis. A systematically comprehensive search was performed through PubMed, EMBASE and CNKI (Chinese National Knowledge Infrastructure). Prognostic value of MUC4 expression in malignancy patients was evaluated by pooled hazard ratios (HRs) and their 95% confidence intervals (CIs). Meanwhile, pooled odds ratio (OR) with 95% CI was appropriate for the association between MUC4 expression and clinicopathological parameters. Eighteen studies including 1,933 patients were enrolled in this meta-analysis. Significant association was found between elevated MUC4 expression and poorer overall survival (OS) with pooled hazard ratio (HR) of 1.87 [95% confidence interval (CI): 1.58-2.23, P<0.001]. Significant associations were also detected in biliary tract carcinoma (HR: 2.41, 95% CI: 1.69-3.42, P<0.001), pancreatic cancer (HR: 2.01, 95% CI: 1.42-2.86, P<0.001) and colorectal cancer (HR: 1.73, 95% CI: 1.17-2.54, P=0.006). Moreover, combined odds ratio (OR) of MUC4 indicated that MUC4 overexpression was associated with tumor stage, tumor invasion and lymph node metastasis. Our results demonstrated that MUC4 may be exploited as a novel prognostic biomarker for cancer patients. PMID:26379819

Significance of the prognostic nutritional index in patients with glioblastoma: A retrospective study.

PubMed

Zhou, Xing-Wang; Dong, Hui; Yang, Yuan; Luo, Jie-Wen; Wang, Xiang; Liu, Yan-Hui; Mao, Qing

2016-12-01

Accumulating evidence demonstrates that prognostic nutritional index(PNI) is linked to the clinical outcome of patients with malignant tumors, but few studies had investigated the clinical significance of PNI in glioblastoma multiforme(GBM). This study aimed to clarify the association between PNI and the clinical outcome of patients with GBM. The clinical data of 84 patients with GBM were retrospectively analyzed. PNI was calculated from the following formula: 10×serum albumin (g/dL)+0.005×total lymphocyte count (per mm 3 ). X-tile software was used to determine the cut-off of PNI and other hematological parameters. GBM patients were dichotomized as two groups based on the PNI cut-off. The optimal PNI cut-off level was 44.4. There were 14 patients with a PNI<44.4 and 70 patients with a PNI≥44.4. The results showed that PNI score was associated with gender, serum albumin, and hemoglobin level. Univariate analysis suggested that age, extent of resection, adjuvant treatment, platelet count and PNI score were predictors of overall survival in patients with GBM. The 1- and 2-survival rates of patients with a PNI<44.4 were 28.60 and 0%, respectively, while the corresponding values for patients with a PNI≥44.4 were 52.90 and 5.70%, respectively. Based on multivariate analysis, a PNI≥44.4 (HR:0.479, 95% CI:0.235-0.975,p=0.042) remained an independent prognostic indicator for a favorable outcome of patients with GBM. Furthermore, patients with a PNI≥44.4 may have a better efficacy of adjuvant treatment than patients with a PNI<44.4 (HR:0.259, 95% CI:0.096-0.700, p=0.008). A PNI>44.4 was an independent prognostic parameter of overall survival in patients with GBM and the efficacy of adjuvant treatment. Interventions aimed at correcting the nutritional and immune status of patients with GBM may, therefore, promote the effectiveness of adjuvant treatment and improve the survival outcomes. Copyright © 2016 Elsevier B.V. All rights reserved.

A Multifactorial Analysis of Melanoma: Prognostic Histopathological Features Comparing Clark's and Breslow's Staging Methods

PubMed Central

Balch, Charles M.; Murad, Tariq M.; Soong, Seng-Jaw; Ingalls, Anna Lee; Halpern, Norman B.; Maddox, William A.

1978-01-01

A multifactorial analysis was used to identify the dominant prognostic variables affecting survival from a computerized data base of 339 melanoma patients treated at this institution during the past 17 years. Five of the 13 parameters examined simultaneously were found to independently influence five year survival rates: 1) pathological stage (I vs II, p = 0.0014), 2) lesion ulceration (present vs absent, p = 0.006), 3) surgical treatment (wide excision vs wide excision plus lymphadenectomy, p = 0.024), 4) melanoma thickness (p = 0.032), and 5) location (upper extremity vs lower extremity vs trunk vs head and neck, p = 0.038). Additional factors considered that had either indirect or no influence on survival rates were clinical stage of disease, age, sex, level of invasion, pigmentation, lymphocyte infiltration, growth pattern, and regression. Most of these latter variables derived their prognostic value from correlation with melanoma thickness, except sex which correlated with location (extremity lesions were more frequent on females, trunk lesions on males). This statistical analysis enabled us to derive a mathematical equation for predicting an individual patient's probability of five year survival. Three categories of risk were delineated by measuring tumor thickness (Breslow microstaging) in Stage I patients: 1) thin melanomas (<0.76 mm) were associated with localized disease and a 100% cure rate: 2) intermediate thickness melanomas (0.76-4.00 mm) had an increasing risk (up to 80%) of harboring regional and/or distant metastases and 3) thick melanomas (≥4.00 mm) had a 80% risk of occult distant metastases at the time of initial presentation. The level of invasion (Clark's microstaging) correlated with survival, but was less predictive than measuring tumor thickness. Within each of Clark's Level II, III and IV groups, there were gradations of thickness with statistically different survival rates. Both microstaging methods (Breslow and Clark) were less predictive factors in patients with lymph node or distant metastases. Clinical trials evaluating alternative surgical treatments or adjunctive therapy modalities for melanoma patients should incorporate these parameters into their assessment, especially in Stage I (localized) disease where tumor thickness and the anatomical site of the primary melanoma are dominant prognostic factors. PMID:736651

Serum level of CD26 predicts time to first treatment in early B-chronic lymphocytic leukemia.

PubMed

Molica, Stefano; Digiesi, Giovanna; Mirabelli, Rosanna; Cutrona, Giovanna; Antenucci, Anna; Molica, Matteo; Giannarelli, Diana; Sperduti, Isabella; Morabito, Fortunato; Neri, Antonino; Baldini, Luca; Ferrarini, Manlio

2009-09-01

We analyzed the correlation between well-established biological parameters of prognostic relevance in B-cell chronic lymphocytic leukemia (CLL) [i.e. mutational status of the immunoglobulin heavy chain variable region (IgV(H)), ZAP-70- and CD38-expression] and serum levels of CD26 (dipeptidyl peptidase IV, DPP IV) by evaluating the impact of these variables on the time to first treatment (TFT) in a series of 69 previously untreated Binet stage A B-cell CLL patients. By using a commercial ELISA we found that with exception of a borderline significance for ZAP-70 (P = 0.07) and CD38 (P = 0.08), circulating levels of CD26 did not correlate with either Rai substages (P = 0.520) or other biomarker [beta2-microglobulin (P = 0.933), LDH (P = 0.101), mutational status of IgV(H) (P = 0.320)]. Maximally selected log-rank statistic plots identified a CD26 serum concentration of 371 ng/mL as the best cut-off. This threshold allowed the identification of two subsets of patients with CD26 serum levels higher and lower that 371 ng/mL respectively, whose clinical outcome was different with respect to TFT (i.e. 46% and 71% at 5 yr respectively; P = 0.005). Along with higher serum levels of CD26, the univariate Cox proportional hazard model identified absence of mutation in IgV(H) (P < 0.0001) as predictor of shorter TFT. As in multivariate analysis all these parameters maintained their discriminating power (mutational status of IgV(H,)P < 0.0001; soluble CD26, P = 0.02) their combined effect on clinical outcome was assessed. When three groups were considered: (1) Low-risk group (n = 31), patients with concordant IgVH(mut) and low level of soluble CD26; (2) intermediate risk group (n = 26), patients with discordant pattern; (3) high-risk group (n = 12), patients with concordant IgVH(unmut) and high level of soluble CD26, differences in the TFT were statistically significant, with a TFT at 5 yr of respectively 88%, 51% and 43% (P < 0.0001). Our results indicate that in early B-cell CLL biological profile including among other parameters soluble CD26 may provide a useful insight into the complex interrelationship of prognostic variables. Furthermore, CD26 along with mutational status of IgV(H) can be adequately used to predict clinical behavior of patients with low risk disease.

[THE ROLE OF SYSTEM QUORUM SENSING UNDER CHRONIC UROGENITAL CHLAMYDIA INFECTION].

PubMed

2015-10-01

It is established that system quorum sensing (QS) assure social behavior of bacteria in regulation of genes of virulence and generalization of inflectional inflammatory process under chronic urogenital chlamydia infection. The techniques of gas chromatography and mass-spectrometry were applied to detect molecular markers of generalization of infectious process under urogenital chlamydiasis--activators of QS microbes (lactones, quinolones, furan ethers). The developed diagnostic gas chromatography and mass-spectrometry criteria of indexation of molecular markers under chronic urogenital chlamydia infection have high level of diagnostic sensitivity, specificity and prognostic value of positive and negative result. The application of techniques of gas chromatography and mass-spectrometry permits enhancing effectiveness of diagnostic of chronic inflectional inflammatory diseases of urogenital system of chlamydia etiology with identification of prognostic criteria of generalization of infectious process and subsequent prescription of timely and appropriate therapy

Prognostic and predictive value of tumor-infiltrating lymphocytes in two phase III randomized adjuvant breast cancer trials

PubMed Central

Dieci, M. V.; Mathieu, M. C.; Guarneri, V.; Conte, P.; Delaloge, S.; Andre, F.; Goubar, A.

2015-01-01

Background Tumor-infiltrating lymphocytes (TILs) are emerging as strong prognostic factor for early breast cancer patients, especially in the triple-negative subtype. Here, we aim to validate previous findings on the prognostic role of TIL in the context of two randomized adjuvant trials and to investigate whether lymphocyte infiltrates can predict benefit from adjuvant anthracyclines. Patients and methods A total of 816 patients enrolled and treated at the Gustave Roussy in the context of two multicentric randomized trials comparing adjuvant anthracyclines versus no chemotherapy were included in the present analysis. Primary end point was overall survival (OS). Hematoxilin and eosin slides of primary tumors were retrieved and evaluated for the percentage of intratumoral (It) and stromal (Str) TIL. Each case was also defined as high-TIL or low-TIL breast cancer adopting previously validated cutoffs. Results TIL were assessable for 781 of 816 cases. High-TIL cases were more likely grade 3 and estrogen receptor (ER)-negative (P < 0.001). In multivariate analysis, both continuous It-TIL and Str-TIL were strong prognostic factors for OS [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77–0.95 P = 0.003; HR 0.89, 95% CI 0.81–0.96, P = 0.005 for It-TIL and Str-TIL, respectively]. The prognostic effect of continuous TIL was limited to triple-negative and HER2-positive patients. Ten-year OS rates were: 89% and 68% for triple-negative high-TIL and low-TIL, respectively (HR 0.44, 95% CI 0.18–1.10, P = 0.07) and 78% and 57% for HER2-positive high-TIL versus low-TIL, respectively (HR 0.46, 95% CI 0.20–1.11, P = 0.08). Either continuous or binary TIL variables did not predict for the efficacy of anthracyclines. Test for interaction P value was not significant in the whole study population and in subgroups (ER+/HER2−, HER2+, ER−/HER2−). Conclusions We confirmed the prognostic role of TIL in triple-negative early breast cancer and suggested a prognostic impact in HER2+ patients as well. Basing on our data, TIL should not be used as a parameter to select patients for anthracyclines chemotherapy. PMID:25995301

Survivin expression in head and neck squamous cell carcinomas is frequent and correlates with clinical parameters and treatment outcomes.

PubMed

Münscher, Adrian; Prochnow, Sebastian; Gulati, Amit; Sauter, Guido; Lörincz, Balazs; Blessmann, Marco; Hanken, Henning; Böttcher, Arne; Clauditz, Till Sebastian

2018-04-18

Strong expression of survivin is associated with worse survival in many different tumours, and in cell culture, a correlation between radiation resistance and survivin expression can be seen. The potential of survivin expression as a prognostic/predictive marker or therapeutic target has not been examined in head and neck squamous cell carcinomas (HNSCC) yet. Retrospective study of 452 tissue samples and clinical data from patients with squamous cell carcinomas of the larynx/hypopharynx (LSCC), oral cavity (OSCC) and oropharynx (OPSCC) treated in the University Medical Centre Hamburg-Eppendorf between 2002 and 2006. The expression patterns were detected by tissue microarray technique and correlated with clinical parameters (sex, age, tumour location, TNM 7th edition, grading, recurrence-free and overall survival). 222 OSCC, 126 OPSCC and 105 LSCC tumours of 118 females and 335 males with a mean follow-up of 41.3 months were examined. Survivin expression correlates with pN, cM, pT and overall survival. The potential of survivin as a prognostic/predictive marker is very high. The findings have to be confirmed in a larger cohort of HNSCC esp. in those tumours treated primarily with radio/radiochemotherapy.

[Cervical cancer : Update on morphology].

PubMed

Horn, L-C; Brambs, C E; Handzel, R; Lax, S; Sändig, I; Schmidt, D; Schierle, K

2016-11-01

The World Health Organization (WHO) classification from 2014 differentiates between different subtypes of mucinous adenocarcinoma of the uterine cervix. A gastric subtype was recently described that showed no association with high-risk human papillomavirus (HPV) infections, has a poor prognosis, is mainly diagnosed in women of Asian origin and can occur in patients with Peutz-Jeghers syndrome. Although no clear grading system has been recommended in the WHO classification, it is likely that grading of adenocarcinomas of the uterine cervix will partly be based on the different patterns of invasion. Deep stromal infiltration of macroinvasive carcinomas is defined as an infiltration of >66 % of the cervical stroma. In the near future a maximum tumor size of 2 cm could act as a discriminator for planning of less radical surgery. Parameters of the histopathological report that are relevant for the prognostic assessment as well as the choice of adjuvant treatment and function as quality indicators during certification are described. The histological type of an adenocarcinoma alone is of no predictive or prognostic relevance for patients undergoing primary surgical treatment, neoadjuvant chemotherapy, combined chemo-radiotherapy or treatment with angiogenesis inhibitors. Currently, molecular parameters and biomarkers are of no relevance.

Goseki grade and tumour location influence survival of patients with gastric cancer.

PubMed

Calik, Muhammet; Calik, Ilknur; Demirci, Elif; Altun, Eren; Gundogdu, Betul; Sipal, Sare; Gundogdu, Cemal

2014-01-01

Owing to the variability of histopathological features and biological behaviour in gastric carcinoma, a great number of categorisation methods such as classical histopathologic grading, Lauren classification, the TNM staging system and the newly presented Goseki grading method are used by pathologists and other scientists. In our study, we aimed to investigate whether Goseki grade and tumour location have an effects on survival of gastric cancer cases. Eighty-four patients with gastric adenocarcinoma were covered in the investigation. The importance of Goseki grading system and tumour location were analysed in addition to the TNM staging and other conventional prognostic parameters. The median survival time in our patients was 35 months (minimum: 5, maximum: 116). According to our findings, there was no relation between survival and tumour size (p=0.192) or classical histological type (p=0.270). In contrast, the Goseki grade and tumour location significantly correlated with survival (p=0.007 and p<0.001, respectively). Additionally, tumours of the intestinal type had a longer median survival time (60.0 months) than diffuse tumours (24.0 months). In addition to the TNM staging system, tumour location and the Goseki grading system may be used as significant prognostic parameters in patients with gastric cancer.

Transcranial Magnetic Stimulation (TMS) as a Tool for Early Diagnosis and Prognostication in Cortico-Basal Ganglia Degeneration (CBD) Syndromes: Review of Literature and Case Report.

PubMed

Issac, Thomas Gregor; Chandra, Sadanandavalli Retnaswami; Nagaraju, B C

2016-01-01

Cortico basal degeneration (CBD) of the brain is a rare progressive neurodegenerative disease which encompasses unique neuropsychiatric manifestations. Early diagnosis is essential for initiating proper treatment and favorable outcome. Transcranial Magnetic Stimulation (TMS), a well-known technique for assessment of cortical excitatory and inhibitory properties. It was suggested that in a degenerative disease like CBD which involves the cortex as well as the subcortical structures, comparing both hemispheres, a differential pattern in TMS can be obtained which would help in early identification, prognostication and early therapeutic intervention. We describe a case of CBD with corroborative clinical and imaging picture wherein single pulse TMS was used over both the hemispheres measuring the following parameters of interest which included: Motor Threshold (MT), Central Motor Conduction Time (CMCT) and Silent Period (SP). Differential patterns of MT, CMCT and SP was obtained by stimulating over both the hemispheres with the affected hemisphere showing significantly reduced MT and prolonged CMCT implying early impairment of cortical and subcortical structures thereby revealing the potential application of TMS being utilized in a novel way for early detection and prognostication in CBD syndromes.

On the Prognostic Efficiency of Topological Descriptors for Magnetograms of Active Regions

NASA Astrophysics Data System (ADS)

Knyazeva, I. S.; Urtiev, F. A.; Makarenko, N. G.

2017-12-01

Solar flare prediction remains an important practical task of space weather. An increase in the amount and quality of observational data and the development of machine-learning methods has led to an improvement in prediction techniques. Additional information has been retrieved from the vector magnetograms; these have been recently supplemented by traditional line-of-sight (LOS) magnetograms. In this work, the problem of the comparative prognostic efficiency of features obtained on the basis of vector data and LOS magnetograms is discussed. Invariants obtained from a topological analysis of LOS magnetograms are used as complexity characteristics of magnetic patterns. Alternatively, the so-called SHARP parameters were used; they were calculated by the data analysis group of the Stanford University Laboratory on the basis of HMI/SDO vector magnetograms and are available online at the website (http://jsoc.stanford.edu/) with the solar dynamics observatory (SDO) database for the entire history of SDO observations. It has been found that the efficiency of large-flare prediction based on topological descriptors of LOS magnetograms in epignosis mode is at least s no worse than the results of prognostic schemes based on vector features. The advantages of the use of topological invariants based on LOS data are discussed.

Protein Z efficiently depletes thrombin generation in disseminated intravascular coagulation with poor prognosis.

PubMed

Lee, Nuri; Kim, Ji-Eun; Gu, Ja-Yoon; Yoo, Hyun Ju; Kim, Inho; Yoon, Sung-Soo; Park, Seonyang; Han, Kyou-Sup; Kim, Hyun Kyung

2016-01-01

Disseminated intravascular coagulation (DIC) is characterized by consumption of coagulation factors and anticoagulants. Thrombin generation assay (TGA) gives useful information about global hemostatic status. We developed a new TGA system that anticoagulant addition can deplete thrombin generation in plasma, which may reflect defective anticoagulant system in DIC. TGAs were measured on the calibrated automated thrombogram with and without thrombomodulin or protein Z in 152 patients who were suspected of having DIC, yielding four parameters including lag time, endogenous thrombin potential, peak thrombin and time-to-peak in each experiment. Nonsurvivors showed significantly prolonged lag time and time-to-peak in TGA-protein Z system, which was performed with added protein Z. In multivariate Cox regression analysis, lag time and time-to-peak in TGA system were significant independent prognostic factors. In TGA-protein Z system, lag time and time-to-peak were revealed as independent prognostic factors of DIC. Protein Z addition could potentiate its anticoagulant effect in DIC with poor prognosis, suggesting the presence of defective protein Z system. The prolonged lag time and time-to-peak in both TGA and TGA-protein Z systems are expected to be used as independent prognostic factors of DIC.

A Comparison of Filter-based Approaches for Model-based Prognostics

NASA Technical Reports Server (NTRS)

Daigle, Matthew John; Saha, Bhaskar; Goebel, Kai

2012-01-01

Model-based prognostics approaches use domain knowledge about a system and its failure modes through the use of physics-based models. Model-based prognosis is generally divided into two sequential problems: a joint state-parameter estimation problem, in which, using the model, the health of a system or component is determined based on the observations; and a prediction problem, in which, using the model, the stateparameter distribution is simulated forward in time to compute end of life and remaining useful life. The first problem is typically solved through the use of a state observer, or filter. The choice of filter depends on the assumptions that may be made about the system, and on the desired algorithm performance. In this paper, we review three separate filters for the solution to the first problem: the Daum filter, an exact nonlinear filter; the unscented Kalman filter, which approximates nonlinearities through the use of a deterministic sampling method known as the unscented transform; and the particle filter, which approximates the state distribution using a finite set of discrete, weighted samples, called particles. Using a centrifugal pump as a case study, we conduct a number of simulation-based experiments investigating the performance of the different algorithms as applied to prognostics.

Bone marrow fibrosis in myelodysplastic syndromes: a prospective evaluation including mutational analysis

PubMed Central

Ramos, Fernando; Robledo, Cristina; Izquierdo-García, Francisco Miguel; Suárez-Vilela, Dimas; Benito, Rocío; Fuertes, Marta; Insunza, Andrés; Barragán, Eva; del Rey, Mónica; de Morales, José María García-Ruiz; Tormo, Mar; Salido, Eduardo; Zamora, Lurdes; Pedro, Carmen; Sánchez-del-Real, Javier; Díez-Campelo, María; del Cañizo, Consuelo; Sanz, Guillermo F.; Hernández-Rivas, Jesús María

2016-01-01

The biological and molecular events that underlie bone marrow fibrosis in patients with myelodysplastic syndromes are poorly understood, and its prognostic role in the era of the Revised International Prognostic Scoring System (IPSS-R) is not yet fully determined. We have evaluated the clinical and biological events that underlie bone marrow fibrotic changes, as well as its prognostic role, in a well-characterized prospective patient cohort (n=77) of primary MDS patients. The degree of marrow fibrosis was linked to parameters of erythropoietic failure, marrow cellularity, p53 protein accumulation, WT1 gene expression, and serum levels of CXCL9 and CXCL10, but not to other covariates including the IPSS-R score. The presence of bone marrow fibrosis grade 2 or higher was associated with the presence of mutations in cohesin complex genes (31.5% vs. 5.4%, p=0.006). By contrast, mutations in CALR, JAK2, PDGFRA, PDGFRB, and TP53 were very rare. Survival analysis showed that marrow fibrosis grade 2 or higher was a relevant significant predictor for of overall survival, and independent of age, performance status, and IPSS-R score in multivariate analysis. PMID:27127180

Long non-coding RNA HULC as a potential prognostic biomarker in human cancers: a meta-analysis.

PubMed

Fan, Yang-Hua; Wu, Miao-Jing; Jiang, Yuan; Ye, Minhua; Lu, Shi-Gang; Wu, Lei; Zhu, Xin-Gen

2017-03-28

Since the long non-coding RNA HULC (Highly Upregulated in Liver Cancer) is dysregulated in many cancers, we performed a meta-analysis to determine its prognostic potential in malignant tumors. We searched electronic databases, including PubMed, Medline, OVID, Cochrane Library and Web of Science from inception until August 14, 2016 and identified seven studies with 730 cancer patients for the meta-analysis. We analyzed the hazard ratios (HRs) and 95% confidence intervals (CIs) to determine the relationship between HULC expression and overall survival (OS). We also using RevMan5.3 software to calculate odds ratio (ORs) to assess the association between HULC expression and pathological parameters, including lymph node metastasis (LNM), distant metastasis (DM) and the tumor stage. Our analysis showed that higher HULC expression was associated with OS (HR= 0.50, 95% CI: 0.35-0.70, P <0.00001), LNM (OR=0.20, 95 % CI 0.06-0.64), DM (OR=0.27, 95% CI: 0.13-0.54) and the tumor stage (OR=0.39, 95 % CI 0.25-0.64). These meta-analysis data demonstrate that higher HULC expression can be a useful prognostic biomarker in human cancers.

Normalization for peak oxygen uptake increases the prognostic power of the ventilatory response to exercise in patients with chronic heart failure.

PubMed

Guazzi, Marco; De Vita, Stefano; Cardano, Paola; Barlera, Simona; Guazzi, Maurizio D

2003-09-01

Peak exercise oxygen uptake (peak VO2) and ventilation to CO2 production (VE/VCO2) slope are established prognostic indicators in patients with chronic heart failure (CHF). A high VE/VCO2 slope, however, does not take into account the level of physical performance as expressed by peak VO2. We hypothesized that the prognostic value of a high VE/VCO2 slope may be improved by normalization for peak VO2 (VE/VCO2/VO2). One hundred patients with CHF underwent pulmonary function tests at rest (spirometry and lung diffusion capacity) and maximal cardiopulmonary exercise testing. The prognostic value of VE/VCO2 slope, peak VO2 and VE/VCO2/VO2 was probed prospectively. Twenty-one patients died from cardiac reasons during a mean follow-up of 26 +/- 19 months. Nonsurvivors, compared to survivors, showed a lower peak VO2 (13.6 +/- 4.0 vs 17.5 +/- 4.1 mL x min(-1) x kg(-1), P <.01) and a steeper VE/VCO2 slope (43 +/- 11 vs 31.6 +/- 5.0, P <.01). Nonetheless, in patients whose VE/VCO2 slope exceeded 34 (upper normal limit), there was no correlation with peak VO2 (r = -35, P = not significant). Interestingly 35% of them showed a normal exercise performance (peak VO2 > or =18 mL x min(-1) x kg(-1)). At multivariate analysis, the VE/VCO2 slope showed a prognostic power stronger than that of peak VO2; however, the VE/VCO2/VO2 index retained a prognostic power greater than that of both VE/VCO2 slope and peak VO2. A VE/VCO2/VO2 > or =2.4 signaled cases at higher risk. Discrepancies between VE/VCO2 slope and peak VO2 may generate uncertainty. Normalization of the former by the latter improves outcome prediction and may be considered a simple and effective way for maximizing the clinical applicability of these 2 indicators.

[68Ga]Pentixafor-PET/CT for imaging of chemokine receptor CXCR4 expression in multiple myeloma - Comparison to [18F]FDG and laboratory values.

PubMed

Lapa, Constantin; Schreder, Martin; Schirbel, Andreas; Samnick, Samuel; Kortüm, Klaus Martin; Herrmann, Ken; Kropf, Saskia; Einsele, Herrmann; Buck, Andreas K; Wester, Hans-Jürgen; Knop, Stefan; Lückerath, Katharina

2017-01-01

Chemokine (C-X-C motif) receptor 4 (CXCR4) is a key factor for tumor growth and metastasis in several types of human cancer including multiple myeloma (MM). Proof-of-concept of CXCR4-directed radionuclide therapy in MM has recently been reported. This study assessed the diagnostic performance of the CXCR4-directed radiotracer [ 68 Ga]Pentixafor in MM and a potential role for stratifying patients to CXCR4-directed therapies. Thirty-five patients with MM underwent [ 68 Ga]Pentixafor-PET/CT for evaluation of eligibility for endoradiotherapy. In 19/35 cases, [ 18 F]FDG-PET/CT for correlation was available. Scans were compared on a patient and on a lesion basis. Tracer uptake was correlated with standard clinical parameters of disease activity. [ 68 Ga]Pentixafor-PET detected CXCR4-positive disease in 23/35 subjects (66%). CXCR4-positivity at PET was independent from myeloma subtypes, cytogenetics or any serological parameters and turned out as a negative prognostic factor. In the 19 patients in whom a comparison to [ 18 F]FDG was available, [ 68 Ga]Pentixafor-PET detected more lesions in 4/19 (21%) subjects, [ 18 F]FDG proved superior in 7/19 (37%). In the remaining 8/19 (42%) patients, both tracers detected an equal number of lesions. [ 18 F]FDG-PET positivity correlated with [ 68 Ga]Pentixafor-PET positivity (p=0.018). [ 68 Ga]Pentixafor-PET provides further evidence that CXCR4 expression frequently occurs in advanced multiple myeloma, representing a negative prognostic factor and a potential target for myeloma specific treatment. However, selecting patients for CXCR4 directed therapies and prognostic stratification seem to be more relevant clinical applications for this novel imaging modality, rather than diagnostic imaging of myeloma.

Dynamic Contrast-Enhanced Magnetic Resonance Imaging as a Predictor of Outcome in Head-and-Neck Squamous Cell Carcinoma Patients With Nodal Metastases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shukla-Dave, Amita, E-mail: davea@mskcc.org; Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY; Lee, Nancy Y.

2012-04-01

Purpose: Dynamic contrast-enhanced MRI (DCE-MRI) can provide information regarding tumor perfusion and permeability and has shown prognostic value in certain tumors types. The goal of this study was to assess the prognostic value of pretreatment DCE-MRI in head and neck squamous cell carcinoma (HNSCC) patients with nodal disease undergoing chemoradiation therapy or surgery. Methods and Materials: Seventy-four patients with histologically proven squamous cell carcinoma and neck nodal metastases were eligible for the study. Pretreatment DCE-MRI was performed on a 1.5T MRI. Clinical follow-up was a minimum of 12 months. DCE-MRI data were analyzed using the Tofts model. DCE-MRI parameters weremore » related to treatment outcome (progression-free survival [PFS] and overall survival [OS]). Patients were grouped as no evidence of disease (NED), alive with disease (AWD), dead with disease (DOD), or dead of other causes (DOC). Prognostic significance was assessed using the log-rank test for single variables and Cox proportional hazards regression for combinations of variables. Results: At last clinical follow-up, for Stage III, all 12 patients were NED. For Stage IV, 43 patients were NED, 4 were AWD, 11 were DOD, and 4 were DOC. K{sup trans} is volume transfer constant. In a stepwise Cox regression, skewness of K{sup trans} (volume transfer constant) was the strongest predictor for Stage IV patients (PFS and OS: p <0.001). Conclusion: Our study shows that skewness of K{sup trans} was the strongest predictor of PFS and OS in Stage IV HNSCC patients with nodal disease. This study suggests an important role for pretreatment DCE-MRI parameter K{sup trans} as a predictor of outcome in these patients.« less

Development of a clinical applicable graphical user interface to automatically detect exercise oscillatory ventilation: The VOdEX-tool.

PubMed

Cornelis, Justien; Denis, Tim; Beckers, Paul; Vrints, Christiaan; Vissers, Dirk; Goossens, Maggy

2017-08-01

Cardiopulmonary exercise testing (CPET) gained importance in the prognostic assessment of especially patients with heart failure (HF). A meaningful prognostic parameter for early mortality in HF is exercise oscillatory ventilation (EOV). This abnormal respiratory pattern is recognized by hypo- and hyperventilation during CPET. Up until now, assessment of EOV is mainly done upon visual agreement or manual calculation. The purpose of this research was to automate the interpretation of EOV so this prognostic parameter could be readily investigated during CPET. Preliminary, four definitions describing the original characteristics of EOV, were selected and integrated in the "Ventilatory Oscillations during Exercise-tool" (VOdEX-tool), a graphical user interface that allows automate calculation of EOV. A Discrete Meyer Level 2 wavelet transformation appeared to be the optimal filter to apply on the collected breath-by-breath minute ventilation CPET data. Divers aspects of the definitions i.e. cycle length, amplitude, regularity and total duration of EOV were combined and calculated. The oscillations meeting the criteria were visualised. Filter methods and cut-off criteria were made adjustable for clinical application and research. The VOdEX-tool was connected to a database. The VOdEX-tool provides the possibility to calculate EOV automatically and to present the clinician an overview of the presence of EOV at a glance. The computerized analysis of EOV can be made readily available in clinical practice by integrating the tool in the manufactures existing CPET software. The VOdEX-tool enhances assessment of EOV and therefore contributes to the estimation of prognosis in especially patients with HF. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Aldehyde dehydrogenase 1 (ALDH1) expression is an independent prognostic factor in triple negative breast cancer (TNBC).

PubMed

Ma, Fei; Li, Huihui; Li, Yiqun; Ding, Xiaoyan; Wang, Haijuan; Fan, Ying; Lin, Chen; Qian, Haili; Xu, Binghe

2017-04-01

Triple negative breast cancer (TNBC) is a subset of breast cancer that is highly aggressive and has a poor prognosis. Meanwhile, cancer stem cells (CSCs) are also characterized by a strong tumorigenic potential, which might be partly responsible for the aggressive behavior of TNBC. We previously showed that CSCs are enriched in TNBC cell lines and tissues. Further experiments in animal models revealed higher tumorigenicity of CSCs sorted from TNBC cell lines. In this study, we aimed to determine the clinical relationship between CSCs and TNBC by exploring the expression of aldehyde dehydrogenase 1 (ALDH1), which is a putative marker of breast CSCs, in TNBC tissues.ALDH1 levels in paraffin-embedded tumor tissues from 158 TNBC patients were evaluated by immunohistochemistry staining using an ALDH1A1 primary antibody. Staining evaluation was performed independently by two pathologists, and the expression level of ALDH1 was evaluated in terms of the percentage and intensity of positive cells. The association of immunohistochemistry staining of ALDH1 expression with clinical parameters was also analyzed.ALDH1 expression in tumor cells was observed in 88 out of 158 cases (55.7%). Analysis of clinicopathological parameters showed that the immunohistochemistry staining of ALDH1 was significantly correlated with tumor size (P = 0.02) and stage (P = 0.04). Survival analysis in patients with ALDH1 expression demonstrated shorter relapse-free survival (RFS) and overall survival (OS) times (P = 0.01; P = 0.001). Moreover, Cox multivariate analysis revealed that ALDH1 expression was an independent prognostic indicator of RFS and OS (P = 0.04; P = 0.04).Immunohistochemistry staining of ALDH1 in tumor cells is an independent prognostic indicator of RFS and OS in TNBC patients.

Prognostic capacity of a clinically indicated exercise test for cardiovascular mortality is enhanced by combined analysis of exercise capacity, heart rate recovery and T-wave alternans.

PubMed

Minkkinen, Mikko; Nieminen, Tuomo; Verrier, Richard L; Leino, Johanna; Lehtimäki, Terho; Viik, Jari; Lehtinen, Rami; Nikus, Kjell; Kööbi, Tiit; Turjanmaa, Väinö; Kähönen, Mika

2015-09-01

Exercise capacity, heart rate recovery and T-wave alternans are independent predictors of cardiovascular mortality. We tested whether these parameters contain supplementary prognostic information. A total of 3609 consecutive patients (2157 men) referred for a routine, clinically indicated bicycle exercise test were enrolled in the Finnish Cardiovascular Study (FINCAVAS). Exercise capacity was measured in metabolic equivalents, heart rate recovery as the decrease in heart rate from maximum to one minute post-exercise, and T-wave alternans by time-domain Modified Moving Average method. During 57-month median follow-up (interquartile range 35-78 months), 96 patients died of cardiovascular causes (primary endpoint) and 233 from any cause. All three parameters were independent predictors of cardiovascular mortality when analysed as continuous variables. Adding metabolic equivalents (p < 0.001), heart rate recovery (p = 0.002) or T-wave alternans (p = 0.01) to the linear model improved its predictive power for cardiovascular mortality. The combination of low exercise capacity (<6 metabolic equivalents), reduced heart rate recovery (≤12 beats/min) and elevated T-wave alternans (≥60 μV) yielded the highest hazard ratio for cardiovascular mortality of 16.5 (95% confidence interval 4.0-67.7, p < 0.001). Harrell's C index was 0.719 (confidence interval 0.665-0.772) for cardiovascular mortality with previously defined cutpoints (<8 units for metabolic equivalents, ≤18 beats/min for heart rate recovery and ≥60 μV for T-wave alternans). The prognostic capacity of the clinical exercise test is enhanced by combined analysis of exercise capacity, heart rate recovery and T-wave alternans. © The European Society of Cardiology 2014.

Factors prognostic for phonetic development after cleft palate repair.

PubMed

Lee, Joon Seok; Kim, Jae Bong; Lee, Jeong Woo; Yang, Jung Dug; Chung, Ho Yun; Cho, Byung Chae; Choi, Kang Young

2015-10-01

Palatoplasty is aimed to achieve normal speech, improve food intake, and ensure successful maxillary growth. However, the velopharyngeal function is harder to control than other functions. Therefore, many studies on the prognostic factor of velopharyngeal insufficiency have been conducted. This study aimed to evaluate the relationships between speech outcomes and multimodality based on intraoral and preoperative three-dimensional computerized tomographic (CT) findings. Among 73 children with cleft palate who underwent palatoplasty between April 2011 and August 2014 at Kyungpook National University Hospital (KNUH), 27 were retrospectively evaluated. The 27 cases were non-syndromic, for which successful speech evaluation was conducted by a single speech-language pathologist (Table 1). Successful speech evaluation was defined as performing the test three times in 6-month intervals. Three intraoral parameters were measured before and immediately after operation (Fig. 1). On axial- and coronal-view preoperative facial CT, 5 and 2 different parameters were analyzed, respectively (Figs. 2 and 3). Regression analysis (SPSS IBM 22.0) was used in the statistical analysis. Two-flap palatoplasty and Furlow's double opposing Z-plasty were performed in 15 and 12 patients, respectively. The operation was performed 11 months after birth on average. Children with a higher palatal arch and wider maxillary tuberosity distance showed hypernasality (p < 0.05; Table 2). The useful prognostic factors of velopharyngeal function after palatoplasty were palate width and height, rather than initial diagnosis, treatment method, or palate length. Therefore, a more active intervention is needed, such as orthopedic appliance, posterior pharyngeal wall augmentation, or early speech training. Copyright © 2015 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Dynamic imaging response following radiation therapy predicts long-term outcomes for diffuse low-grade gliomas.

PubMed

Pallud, Johan; Llitjos, Jean-François; Dhermain, Frédéric; Varlet, Pascale; Dezamis, Edouard; Devaux, Bertrand; Souillard-Scémama, Raphaëlle; Sanai, Nader; Koziak, Maria; Page, Philippe; Schlienger, Michel; Daumas-Duport, Catherine; Meder, Jean-François; Oppenheim, Catherine; Roux, François-Xavier

2012-04-01

Quantitative imaging assessment of radiation therapy (RT) for diffuse low-grade gliomas (DLGG) by measuring the velocity of diametric expansion (VDE) over time has never been studied. We assessed the VDE changes following RT and determined whether this parameter can serve as a prognostic factor. We reviewed a consecutive series of 33 adults with supratentorial DLGG treated with first-line RT with available imaging follow-up (median follow-up, 103 months). Before RT, all patients presented with a spontaneous tumor volume increase (positive VDE, mean 5.9 mm/year). After RT, all patients demonstrated a tumor volume decrease (negative VDE, mean, -16.7 mm/year) during a mean 49-month duration. In univariate analysis, initial tumor volume (>100 cm(3)), lack of IDH1 expression, p53 expression, high proliferation index, and fast post-RT tumor volume decrease (VDE at -10 mm/year or faster, fast responders) were associated with a significantly shorter overall survival (OS). The median OS was significantly longer (120.8 months) for slow responders (post-RT VDE slower than -10.0 mm/year) than for fast responders (47.9 months). In multivariate analysis, fast responders, larger initial tumor volume, lack of IDH1 expression, and p53 expression were independent poor prognostic factors for OS. A high proliferation index was significantly more frequent in the fast responder subgroup than in the slow responder subgroup. We conclude that the pattern of post-RT VDE changes is an independent prognostic factor for DLGG and offers a quantitative parameter to predict long-term outcomes. We propose to monitor individually the post-RT VDE changes using MRI follow-up, with particular attention to fast responders.

Dynamic imaging response following radiation therapy predicts long-term outcomes for diffuse low-grade gliomas

PubMed Central

Pallud, Johan; Llitjos, Jean-François; Dhermain, Frédéric; Varlet, Pascale; Dezamis, Edouard; Devaux, Bertrand; Souillard-Scémama, Raphaëlle; Sanai, Nader; Koziak, Maria; Page, Philippe; Schlienger, Michel; Daumas-Duport, Catherine; Meder, Jean-François; Oppenheim, Catherine; Roux, François-Xavier

2012-01-01

Quantitative imaging assessment of radiation therapy (RT) for diffuse low-grade gliomas (DLGG) by measuring the velocity of diametric expansion (VDE) over time has never been studied. We assessed the VDE changes following RT and determined whether this parameter can serve as a prognostic factor. We reviewed a consecutive series of 33 adults with supratentorial DLGG treated with first-line RT with available imaging follow-up (median follow-up, 103 months). Before RT, all patients presented with a spontaneous tumor volume increase (positive VDE, mean 5.9 mm/year). After RT, all patients demonstrated a tumor volume decrease (negative VDE, mean, −16.7 mm/year) during a mean 49-month duration. In univariate analysis, initial tumor volume (>100 cm3), lack of IDH1 expression, p53 expression, high proliferation index, and fast post-RT tumor volume decrease (VDE at −10 mm/year or faster, fast responders) were associated with a significantly shorter overall survival (OS). The median OS was significantly longer (120.8 months) for slow responders (post-RT VDE slower than −10.0 mm/year) than for fast responders (47.9 months). In multivariate analysis, fast responders, larger initial tumor volume, lack of IDH1 expression, and p53 expression were independent poor prognostic factors for OS. A high proliferation index was significantly more frequent in the fast responder subgroup than in the slow responder subgroup. We conclude that the pattern of post-RT VDE changes is an independent prognostic factor for DLGG and offers a quantitative parameter to predict long-term outcomes. We propose to monitor individually the post-RT VDE changes using MRI follow-up, with particular attention to fast responders. PMID:22416109

Prognostic significance of epidermal growth factor receptor in surgically treated squamous cell lung cancer patients.

PubMed

Niemiec, Joanna; Kołodziejski, Leszek; Dyczek, Sonia; Gasińska, Anna

2004-01-01

Epidermal growth factor receptor (EGFR) is one of signalling pathways activated during premalignant proliferative changes in the airway epithelium. However there is no agreement about prognostic significance of EGFR expression in non-small cell lung cancer (NSCLC). Facts mentioned above prompted us to study EGFR expression in the group of 78 surgically treated squamous cell lung cancer (SqCLC) patients. The EGFR expression was visualized in formalin-fixed, paraffin-embedded sections, using immunohistochemistry. Three methods of assessment of EGFR expression were applied: percentage of cells with membranous EGFR expression--EGFR labellig index (EGFR LI), percentage of fields with membranous EGFR staining (PS%) and staining intensity (absent, weak or strong) in the whole specimen (SI). Mean EGFR LI and PS% values were 30.4 +/- 3.5% and 51.6 +/- 3.9%, respectively. Patients with higher EGFR expression (EGFR LI, PS%, SI) were significantly younger than those with low EGFR expression. EGFR LI was higher in pT3 tumours than in pT1+pT2 tumours, moreover, EGFR expression (EGFR LI, PS%, SI) was significantly higher in G1+G2 tumours than in G3 tumours. There were significant correlations between parameters used for assessment of EGFR expression. PS% < or = 50 indicated shorter disease-specific survival than PS% > 50. However, patients with tumours with both very low and very high EGFR LI (13% > or = EGFR LI > 80%) showed significantly shorter survival than those with medium EGFR LI (13% < GFR LI < or = 80%). Additionally, pTNM and pN significantly influenced patients' survival. In multivariate analysis, EGFR LI and pTNM were independent prognostic parameters influencing disease-specific survival of patients.

[The prognostic value of cardio-pulmonary exercise test parameters in patients with asymptomatic ischemic heart dysfunction during 2-years observation].

PubMed

Skrzypek, Agnieszka; Nessler, Jadwiga

2015-01-01

Measurement of oxygen uptake at the maximal exercise (VO2max) in the cardio-pulmonary exercise test provides the most reliable information about exertion tolerance. Establishment of VO2peak, VE/CO2 and AT value in the early diagnosis of asymptomatic heart dysfunction in patients with coronary disease (CAD) and prognosis during 2-years observation. The study population: 57 patients (35 M) with CAD, without any signs or symptoms of heart dysfunction, without any features of myocardial infarction, in the age 51.08 +/- 4.01. The analysis was performed twice: in the beginning and after 2-years observation. Physical examinations, echocardiographic parameters [(assessment of systolic and diastolic dysfunction of the left ventricle (LV)] and spiroergometric parameters (VO2peak, VE/CO2 at AT). On the basis of echocardiographic examination, there were created groups of patients: Group A--the patients with normal LV function (n=32; 56.2%; 23 M); Group B--the patients with diastolic heart dysfunction (n=22; 38.6%; 10 M); Group A--32 patients in the age of 50.9 +/- 4, 23 men. Values of VO2pe ak :28.8 +/- 6 ml/kg/min, VE/CO2 28.8 +/- 4.9 and AT 18 +/- 2.5. Group B--the patients with diastolic heart dysfunction: 22 (39%) patients; 10 men, in the age of 51.2 +/- 4.3. Values of VO2peak: 26 +/- 3.4 mi/ kg/min, VE/CO2 31.2 +/- 5.1 and AT 16 +/- 2.5. In the beginning of the study was established significantly differences between anaerobic threshold and degree of heart dysfunction (p=0.039). (1) There was observed that VO2 A and VE/CO2 depended on filling LV profile LV and also of systolic LV function. Anaerobic threshold significantly depended on LV filling pattern. (2) In asymptomatic patients with LV diastolic dysfunction and VO2peak < or = 18.4 ml/kg/min was observed progression of LV diastolic dysfunction during two years.

Dual Roles of RNF2 in Melanoma Progression | Office of Cancer Genomics

Cancer.gov

Epigenetic regulators have emerged as critical factors governing the biology of cancer. Here, in the context of melanoma, we show that RNF2 is prognostic, exhibiting progression-correlated expression in human melanocytic neoplasms. Through a series of complementary gain-of-function and loss-of-function studies in mouse and human systems, we establish that RNF2 is oncogenic and prometastatic.

Predictive and prognostic value of 18F-DOPA PET/CT in patients affected by recurrent medullary carcinoma of the thyroid.

PubMed

Caobelli, Federico; Chiaravalloti, Agostino; Evangelista, Laura; Saladini, Giorgio; Schillaci, Orazio; Vadrucci, Manuela; Scalorbi, Federica; Donner, Davide; Alongi, Pierpaolo

2018-01-01

Medullary thyroid carcinoma (MTC) is a malignancy accounting for about 5-8% of thyroid cancers. Serum calcitonin and carcinoembryonic antigen (CEA) levels are widely used to monitor disease progression. However, prognostic factors able to predict outcomes are highly desirable. We, therefore, aimed to assess the prognostic role of 18 F-DOPA PET/CT in patients with recurrent MTC. 60 patients (mean age 64 ± 13 years, range 44-82) with recurrent MTC were eligible from a multicenter database. All patients underwent a restaging 18 F-DOPA PET/CT, performed at least 6 months after surgery. CEA/calcitonin levels, local recurrences, nodal involvement and metastases at PET/CT were recorded. SUVmax, SUVmean (also normalized to mediastinal uptake) and metabolic tumor volume were automatically calculated for each lesion, by placing a volume of interest around the lesion with 40% of peak activity as threshold for the automatic contouring. The patients were clinically and radiologically followed up for 21 ± 11 months. Rate of progression-free survival (PFS), disease-specific survival (DSS) and incremental prognostic value of 18 F-DOPA PET/CT over conventional imaging modalities were assessed by Kaplan-Meier curves and Log-Rank test. Cox regression univariate and multivariate analyses were performed for assessing predictors of prognosis. 18 F-DOPA PET/CT showed abnormal findings in 27 patients (45%) and resulted unremarkable in 33 (55%). PFS was significantly longer in patients with an unremarkable PET/CT scan (p = 0.018). Similarly, an unremarkable PET/CT study was associated with a significantly longer DSS (p = 0.04). 18 F-DOPA PET/CT added prognostic value over other imaging modalities both for PFS and for DSS (p < 0.001 and p = 0.012, respectively). Neither semiquantitative PET parameters nor clinical or laboratory data were predictive of a worse PFS and DSS in patients with recurrent MTC. 18 F-DOPA PET/CT scan has an important prognostic value in predicting disease progression and mortality rate.

Sub-classification of Advanced-Stage Hepatocellular Carcinoma: A Cohort Study Including 612 Patients Treated with Sorafenib.

PubMed

Yoo, Jeong-Ju; Chung, Goh Eun; Lee, Jeong-Hoon; Nam, Joon Yeul; Chang, Young; Lee, Jeong Min; Lee, Dong Ho; Kim, Hwi Young; Cho, Eun Ju; Yu, Su Jong; Kim, Yoon Jun; Yoon, Jung-Hwan

2018-04-01

Advanced hepatocellular carcinoma (HCC) is associated with various clinical conditions including major vessel invasion, metastasis, and poor performance status. The aim of this study was to establish a prognostic scoring system and to propose a sub-classification of the Barcelona-Clinic Liver Cancer (BCLC) stage C. This retrospective study included consecutive patientswho received sorafenib for BCLC stage C HCC at a single tertiary hospital in Korea. A Cox proportional hazard model was used to develop a scoring system, and internal validationwas performed by a 5-fold cross-validation. The performance of the model in predicting risk was assessed by the area under the curve and the Hosmer-Lemeshow test. A total of 612 BCLC stage C HCC patients were sub- classified into strata depending on their performance status. Five independent prognostic factors (Child-Pugh score, α-fetoprotein, tumor type, extrahepatic metastasis, and portal vein invasion) were identified and used in the prognostic scoring system. This scoring system showed good discrimination (area under the receiver operating characteristic curve, 0.734 to 0.818) and calibration functions (both p < 0.05 by the Hosmer-Lemeshow test at 1 month and 12 months, respectively). The differences in survival among the different risk groups classified by the total score were significant (p < 0.001 by the log-rank test in both the Eastern Cooperative Oncology Group 0 and 1 strata). The heterogeneity of patientswith BCLC stage C HCC requires sub-classification of advanced HCC. A prognostic scoring system with five independent factors is useful in predicting the survival of patients with BCLC stage C HCC.

Predictive Factors of Surgical Outcome in Frontal Lobe Epilepsy Explored with Stereoelectroencephalography.

PubMed

Bonini, Francesca; McGonigal, Aileen; Scavarda, Didier; Carron, Romain; Régis, Jean; Dufour, Henry; Péragut, Jean-Claude; Laguitton, Virginie; Villeneuve, Nathalie; Chauvel, Patrick; Giusiano, Bernard; Trébuchon, Agnès; Bartolomei, Fabrice

2017-06-29

Resective surgery established treatment for pharmacoresistant frontal lobe epilepsy (FLE), but seizure outcome and prognostic indicators are poorly characterized and vary between studies. To study long-term seizure outcome and identify prognostic factors. We retrospectively analyzed 42 FLE patients having undergone surgical resection, mostly preceded by invasive recordings with stereoelectroencephalography (SEEG). Postsurgical outcome up to 10-yr follow-up and prognostic indicators were analyzed using Kaplan-Meier analysis and multivariate and conditional inference procedures. At the time of last follow-up, 57.1% of patients were seizure-free. The estimated chance of seizure freedom was 67% (95% confidence interval [CI]: 54-83) at 6 mo, 59% (95% CI: 46-76) at 1 yr, 53% (95% CI: 40-71) at 2 yr, and 46% (95% CI: 32-66) at 5 yr. Most relapses (83%) occurred within the first 12 mo. Multivariate analysis showed that completeness of resection of the epileptogenic zone (EZ) as defined by SEEG was the main predictor of seizure outcome. According to conditional inference trees, in patients with complete resection of the EZ, focal cortical dysplasia as etiology and focal EZ were positive prognostic indicators. No difference in outcome was found in patients with positive vs negative magnetic resonance imaging. Surgical resection in drug-resistant FLE can be a successful therapeutic approach, even in the absence of neuroradiologically visible lesions. SEEG may be highly useful in both nonlesional and lesional FLE cases, because complete resection of the EZ as defined by SEEG is associated with better prognosis. Copyright © 2017 by the Congress of Neurological Surgeons

Flow-mediated dilation and cardiovascular event prediction: does nitric oxide matter?

PubMed

Green, Daniel J; Jones, Helen; Thijssen, Dick; Cable, N T; Atkinson, Greg

2011-03-01

Endothelial dysfunction is an early atherosclerotic event that precedes clinical symptoms and may also render established plaque vulnerable to rupture. Noninvasive assessment of endothelial function is commonly undertaken using the flow-mediated dilation (FMD) technique. Some studies indicate that FMD possesses independent prognostic value to predict future cardiovascular events that may exceed that associated with traditional risk factor assessment. It has been assumed that this association is related to the proposal that FMD provides an index of endothelium-derived nitric oxide (NO) function. Interestingly, placement of the occlusion cuff during the FMD procedure alters the shear stress stimulus and NO dependency of the resulting dilation: cuff placement distal to the imaged artery leads to a largely NO-mediated response, whereas proximal cuff placement leads to dilation which is less NO dependent. We used this physiological observation and the knowledge that prognostic studies have used both approaches to examine whether the prognostic capacity of FMD is related to its role as a putative index of NO function. In a meta-analysis of 14 studies (>8300 subjects), we found that FMD derived using a proximal cuff was at least as predictive as that derived using distal cuff placement, despite the latter being more NO dependent. This suggests that, whilst FMD is strongly predictive of future cardiovascular events, this may not solely be related to its assumed NO dependency. Although this finding should be confirmed with more and larger studies, we suggest that any direct measure of vascular (endothelial) function may provide independent prognostic information in humans.

High BAALC expression associates with other molecular prognostic markers, poor outcome, and a distinct gene-expression signature in cytogenetically normal patients younger than 60 years with acute myeloid leukemia: a Cancer and Leukemia Group B (CALGB) study

PubMed Central

Langer, Christian; Radmacher, Michael D.; Ruppert, Amy S.; Whitman, Susan P.; Paschka, Peter; Mrózek, Krzysztof; Baldus, Claudia D.; Vukosavljevic, Tamara; Liu, Chang-Gong; Ross, Mary E.; Powell, Bayard L.; de la Chapelle, Albert; Kolitz, Jonathan E.; Larson, Richard A.; Marcucci, Guido

2008-01-01

BAALC expression is considered an independent prognostic factor in cytogenetically normal acute myeloid leukemia (CN-AML), but has yet to be investigated together with multiple other established prognostic molecular markers in CN-AML. We analyzed BAALC expression in 172 primary CN-AML patients younger than 60 years of age, treated similarly on CALGB protocols. High BAALC expression was associated with FLT3-ITD (P = .04), wild-type NPM1 (P < .001), mutated CEBPA (P = .003), MLL-PTD (P = .009), absent FLT3-TKD (P = .005), and high ERG expression (P = .05). In multivariable analysis, high BAALC expression independently predicted lower complete remission rates (P = .04) when adjusting for ERG expression and age, and shorter survival (P = .04) when adjusting for FLT3-ITD, NPM1, CEBPA, and white blood cell count. A gene-expression signature of 312 probe sets differentiating high from low BAALC expressers was identified. High BAALC expression was associated with overexpression of genes involved in drug resistance (MDR1) and stem cell markers (CD133, CD34, KIT). Global microRNA-expression analysis did not reveal significant differences between BAALC expression groups. However, an analysis of microRNAs that putatively target BAALC revealed a potentially interesting inverse association between expression of miR-148a and BAALC. We conclude that high BAALC expression is an independent adverse prognostic factor and is associated with a specific gene-expression profile. PMID:18378853

High expression of atypical protein kinase C lambda/iota in gastric cancer as a prognostic factor for recurrence.

PubMed

Takagawa, Ryo; Akimoto, Kazunori; Ichikawa, Yasushi; Akiyama, Hirotoshi; Kojima, Yasuyuki; Ishiguro, Hitoshi; Inayama, Yoshiaki; Aoki, Ichiro; Kunisaki, Chikara; Endo, Itaru; Nagashima, Yoji; Ohno, Shigeo

2010-01-01

The atypical protein kinase C lambda/iota (aPKClambda/iota) is involved in several signal transduction pathways that influence cell growth, apoptosis, and the establishment and maintenance of epithelial cell polarity. Overexpression of aPKClambda/iota has been reported in several cancers and been shown to be associated with oncogenesis. However, the expression and role of aPKClambda/iota in gastric cancer, one of the commonest cancers in Asia, have not so far been investigated. This study aimed to clarify the relationship between aPKClambda/iota expression and the clinicopathological features of gastric cancer. Gastric adenocarcinoma samples were obtained from 177 patients who underwent gastrectomy at the Yokohama City University Hospital between 1999 and 2004. Expression of aPKClambda/iota and E: -cadherin was examined immunohistochemically and compared with clinicopathological features of the tumors. Univariate and multivariate analyses were performed for both disease-specific and relapse-free survival. Overexpression of aPKClambda/iota protein was detected in 126 of the 177 (71.2%) gastric cancers. Immunohistological staining for aPKClambda/iota was stronger in gastric adenocarcinoma of intestinal type than diffuse type (p = 0.036), but was not correlated with E: -cadherin expression. A multivariate analysis suggested that nodal metastasis and aPKClambda/iota overexpression were prognostic factors for disease recurrence. Our results suggested that aPKClambda/iota overexpression was a strong prognostic factor for gastric adenocarcinoma recurrence. As well as being a new prognostic indicator, aPKClambda/iota is also likely to be a novel therapeutic target for gastric cancer.

Coronary artery calcium scoring does not add prognostic value to standard 64-section CT angiography protocol in low-risk patients suspected of having coronary artery disease.

PubMed

Kwon, Sung Woo; Kim, Young Jin; Shim, Jaemin; Sung, Ji Min; Han, Mi Eun; Kang, Dong Won; Kim, Ji-Ye; Choi, Byoung Wook; Chang, Hyuk-Jae

2011-04-01

To evaluate the prognostic outcome of cardiac computed tomography (CT) for prediction of major adverse cardiac events (MACEs) in low-risk patients suspected of having coronary artery disease (CAD) and to explore the differential prognostic values of coronary artery calcium (CAC) scoring and coronary CT angiography. Institutional review committee approval and informed consent were obtained. In 4338 patients who underwent 64-section CT for evaluation of suspected CAD, both CAC scoring and CT angiography were concurrently performed by using standard scanning protocols. Follow-up clinical outcome data regarding composite MACEs were procured. Multivariable Cox proportional hazards models were developed to predict MACEs. Risk-adjusted models incorporated traditional risk factors for CAC scoring and coronary CT angiography. During the mean follow-up of 828 days ± 380, there were 105 MACEs, for an event rate of 3%. The presence of obstructive CAD at coronary CT angiography had independent prognostic value, which escalated according to the number of stenosed vessels (P < .001). In the receiver operating characteristic curve (ROC) analysis, the superiority of coronary CT angiography to CAC scoring was demonstrated by a significantly greater area under the ROC curve (AUC) (0.892 vs 0.810, P < .001), whereas no significant incremental value for the addition of CAC scoring to coronary CT angiography was established (AUC = 0.892 for coronary CT angiography alone vs 0.902 with addition of CAC scoring, P = .198). Coronary CT angiography is better than CAC scoring in predicting MACEs in low-risk patients suspected of having CAD. Furthermore, the current standard multisection CT protocol (coronary CT angiography combined with CAC scoring) has no incremental prognostic value compared with coronary CT angiography alone. Therefore, in terms of determining prognosis, CAC scoring may no longer need to be incorporated in the cardiac CT protocol in this population. © RSNA, 2011.

Technical Needs for Prototypic Prognostic Technique Demonstration for Advanced Small Modular Reactor Passive Components

DOE Office of Scientific and Technical Information (OSTI.GOV)

Meyer, Ryan M.; Coble, Jamie B.; Hirt, Evelyn H.

2013-05-17

This report identifies a number of requirements for prognostics health management of passive systems in AdvSMRs, documents technical gaps in establishing a prototypical prognostic methodology for this purpose, and describes a preliminary research plan for addressing these technical gaps. AdvSMRs span multiple concepts; therefore a technology- and design-neutral approach is taken, with the focus being on characteristics that are likely to be common to all or several AdvSMR concepts. An evaluation of available literature is used to identify proposed concepts for AdvSMRs along with likely operational characteristics. Available operating experience of advanced reactors is used in identifying passive components thatmore » may be subject to degradation, materials likely to be used for these components, and potential modes of degradation of these components. This information helps in assessing measurement needs for PHM systems, as well as defining functional requirements of PHM systems. An assessment of current state-of-the-art approaches to measurements, sensors and instrumentation, diagnostics and prognostics is also documented. This state-of-the-art evaluation, combined with the requirements, may be used to identify technical gaps and research needs in the development, evaluation, and deployment of PHM systems for AdvSMRs. A preliminary research plan to address high-priority research needs for the deployment of PHM systems to AdvSMRs is described, with the objective being the demonstration of prototypic prognostics technology for passive components in AdvSMRs. Greater efficiency in achieving this objective can be gained through judicious selection of materials and degradation modes that are relevant to proposed AdvSMR concepts, and for which significant knowledge already exists. These selections were made based on multiple constraints including the analysis performed in this document, ready access to laboratory-scale facilities for materials testing and measurement, and potential synergies with other national laboratory and university partners.« less

The Presence of Vascular Mimicry Predicts High Risk of Clear Cell Renal Cell Carcinoma after Radical Nephrectomy.

PubMed

Zhou, Lin; Chang, Yuan; Xu, Le; Liu, Zheng; Fu, Qiang; Yang, Yuanfeng; Lin, Zongming; Xu, Jiejie

2016-08-01

Vascular mimicry is a type of tumor cell plasticity. The aim of this study was to determine the prognostic value of vascular mimicry in patients with clear cell renal cell carcinoma. We performed a retrospective cohort study in 387 patients with clear cell renal cell carcinoma who underwent radical nephrectomy at Zhongshan Hospital, Fudan University between 2008 and 2009. Pathological features, baseline patient characteristics and followup data were recorded. Vascular mimicry in clear cell renal cell carcinoma tissue was identified by CD31-periodic acid-Schiff double staining. Univariate and multivariate Cox regression models were used to analyze the impact of prognostic factors on recurrence-free survival. The concordance index and the Akaike information criterion were used to assess the predictive accuracy and sufficiency of different models. Positive vascular mimicry staining occurred in 25 of 387 clear cell renal cell carcinoma cases (6.5%) and it was associated with an increased risk of recurrence (log-rank p <0.001). Incorporating vascular mimicry into pT stage, Fuhrman grade and Leibovich score helped refine individual risk stratification. Moreover, vascular mimicry was identified as an independent prognostic factor (p = 0.001). It was entered into a nomogram together with pT stage, Fuhrman grade, tumor size and necrosis. In the primary cohort the Harrell concordance index for the established nomogram to predict recurrence-free survival was slightly higher than that of the Leibovich model (0.850 vs. 0.823), which failed to reach statistical significance (p = 0.158). Vascular mimicry could be a potential prognosticator for recurrence-free survival in patients with clear cell renal cell carcinoma after radical nephrectomy. Further external validation and functional analysis should be pursued to assess its potential prognostic and therapeutic values for clear cell renal cell carcinoma. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Risk stratification using stress echocardiography: incremental prognostic value over historic, clinical, and stress electrocardiographic variables across a wide spectrum of bayesian pretest probabilities for coronary artery disease.

PubMed

Bangalore, Sripal; Gopinath, Devi; Yao, Siu-Sun; Chaudhry, Farooq A

2007-03-01

We sought to evaluate the risk stratification ability and incremental prognostic value of stress echocardiography over historic, clinical, and stress electrocardiographic (ECG) variables, over a wide spectrum of bayesian pretest probabilities of coronary artery disease (CAD). Stress echocardiography is an established technique for the diagnosis of CAD. However, data on incremental prognostic value of stress echocardiography over historic, clinical, and stress ECG variables in patients with known or suggested CAD is limited. We evaluated 3259 patients (60 +/- 13 years, 48% men) undergoing stress echocardiography. Patients were grouped into low (<15%), intermediate (15-85%), and high (>85%) pretest CAD likelihood subgroups using standard software. The historical, clinical, stress ECG, and stress echocardiographic variables were recorded for the entire cohort. Follow-up (2.7 +/- 1.1 years) for confirmed myocardial infarction (n = 66) and cardiac death (n = 105) was obtained. For the entire cohort, an ischemic stress echocardiography study confers a 5.0 times higher cardiac event rate than the normal stress echocardiography group (4.0% vs 0.8%/y, P < .0001). Furthermore, Cox proportional hazard regression model showed incremental prognostic value of stress echocardiography variables over historic, clinical, and stress ECG variables across all pretest probability subgroups (global chi2 increased from 5.1 to 8.5 to 20.1 in the low pretest group, P = .44 and P = .01; from 20.9 to 28.2 to 116 in the intermediate pretest group, P = .47 and P < .0001; and from 17.5 to 36.6 to 61.4 in the high pretest group, P < .0001 for both groups). A normal stress echocardiography portends a benign prognosis (<1% event rate/y) in all pretest probability subgroups and even in patients with high pretest probability and yields incremental prognostic value over historic, clinical, and stress ECG variables across all pretest probability subgroups. The best incremental value is, however, in the intermediate pretest probability subgroup.

Associations between interarm differences in blood pressure and cardiovascular disease outcomes: protocol for an individual patient data meta-analysis and development of a prognostic algorithm.

PubMed

Clark, Christopher E; Boddy, Kate; Warren, Fiona C; Taylor, Rod S; Aboyans, Victor; Cloutier, Lyne; McManus, Richard J; Shore, Angela C; Campbell, John L

2017-07-02

Individual cohort studies in various populations and study-level meta-analyses have shown interarm differences (IAD) in blood pressure to be associated with increased cardiovascular and all-cause mortality. However, key questions remain, such as follows: (1) What is the additional contribution of IAD to prognostic risk estimation for cardiovascular and all-cause mortality? (2) What is the minimum cut-off value for IAD that defines elevated risk? (3) Is there a prognostic value of IAD and do different methods of IAD measurement impact on the prognostic value of IAD? We aim to address these questions by conducting an individual patient data (IPD) meta-analysis. This study will identify prospective cohort studies that measured blood pressure in both arms during recruitment, and invite authors to contribute IPD datasets to this collaboration. All patient data received will be combined into a single dataset. Using one-stage meta-analysis, we will undertake multivariable time-to-event regression modelling, with the aim of developing a new prognostic model for cardiovascular risk estimation that includes IAD. We will explore variations in risk contribution of IAD across predefined population subgroups (eg, hypertensives, diabetics), establish the lower limit of IAD that is associated with additional cardiovascular risk and assess the impact of different methods of IAD measurement on risk prediction. This study will not include any patient identifiable data. Included datasets will already have ethical approval and consent from their sponsors. Findings will be presented to international conferences and published in peer reviewed journals, and we have a comprehensive dissemination strategy in place with integrated patient and public involvement. CRD42015031227. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Evaluation of two prognostic indices for adult T cell leukemia/lymphoma in the subtropical endemic area, Okinawa, Japan.

PubMed

Tamaki, Keita; Morishima, Satoko; Nomura, Shogo; Nishi, Yukiko; Nakachi, Sawako; Kitamura, Sakiko; Uchibori, Sachie; Tomori, Shouhei; Hanashiro, Taeko; Shimabukuro, Natsuki; Tedokon, Iori; Morichika, Kazuho; Taira, Naoya; Tomoyose, Takeaki; Miyagi, Takashi; Karimata, Kaori; Ohama, Masayo; Yamanoha, Atsushi; Tamaki, Kazumitsu; Hayashi, Masaki; Uchihara, Jun-Nosuke; Ohshiro, Kazuiku; Asakura, Yoshitaka; Kuba-Miyara, Megumi; Karube, Kennosuke; Fukushima, Takuya; Masuzaki, Hiroaki

2018-05-17

Aggressive adult T-cell leukemia/lymphoma (ATL) has an extremely poor prognosis and is hyperendemic in Okinawa, Japan. This study evaluated two prognostic indices (PIs) for aggressive ATL, the ATL-PI and Japan Clinical Oncology Group (JCOG)-PI, in a cohort from Okinawa. The PIs were developed using two different Japanese cohorts that included few patients from Okinawa. The endpoint was overall survival (OS). Multivariable Cox regression analyses in the cohort of 433 patients revealed that all seven factors for calculating each PI were statistically significant prognostic predictors. Three-year OS rates for ATL-PI were 35.9% (low-risk, n=66), 10.4% (intermediate-risk, n=256), and 1.6% (high-risk, n=111), and those for JCOG-PI were 22.4% (moderate-risk, n=176) and 5.3% (high-risk, n=257). The JCOG-PI moderate-risk group included both the ATL-PI low- and intermediate-risk groups. ATL-PI more clearly identified the low-risk patient subgroup than JCOG-PI. To evaluate the external validity of the two PIs, we also assessed prognostic discriminability among 159 patients who loosely met the eligibility criteria of a previous clinical trial. Three-year OS rates for ATL-PI were 34.5% (low-risk, n=42), 9.2% (intermediate-risk, n=109), and 12.5% (high-risk, n = 8). Those for JCOG-PI were 22.4% (moderate-risk, n=95) and 7.6% (high-risk, n=64). The low-risk ATL-PI group had a better prognosis than the JCOG-PI moderate-risk group, suggesting that ATL-PI would be more useful than JCOG-PI for establishing and examining novel treatment strategies for ATL patients with a better prognosis. In addition, strongyloidiasis, previously suggested to be associated with ATL-related deaths in Okinawa, was not a prognostic factor in this study. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Prognostic impact of location and extent of vessel-related ischemia at myocardial perfusion scintigraphy in patients with or at risk for coronary artery disease.

PubMed

Nudi, Francesco; Schillaci, Orazio; Neri, Giandomenico; Pinto, Annamaria; Procaccini, Enrica; Vetere, Maurizio; Frati, Giacomo; Tomai, Fabrizio; Biondi-Zoccai, Giuseppe

2016-04-01

Myocardial perfusion scintigraphy (MPS) has an established diagnostic and prognostic role in patients with or at risk for coronary artery disease, with ischemia severity and extent having already been identified as key predictors. Whether this is affected by the location of myocardial ischemia is uncertain. We aimed at comparing the prognostic outlook of patients undergoing MPS according to the site of ischemia. Our institutional database was queried for subjects undergoing MPS, without myocardial necrosis or recent revascularization. We focused on the prognostic impact of location of vessel-related ischemia (VRI) at MPS, distinguishing four mutually exclusive groups: single-VRI involving left anterior descending (LAD), single-VRI not involving LAD, multi-VRI involving LAD, and multi-VRI not involving LAD. The primary outcome was the long-term (>1 year) rate of death or myocardial infarction (D/MI). A total of 13,254 patients were included. Moderate or severe VRI occurred in 2,627 (20%) patients. Clinical outcomes were significantly different among the groups of patients with moderate or severe VRI, including death, cardiac death, non-fatal myocardial infarction or their composites (overall P < .001). Specifically, and excluding subjects undergoing revascularization as first follow-up event, D/MI occurred in 8.4% of patients with single-VRI involving LAD, 5.5% of subjects with single-VRI not involving LAD, 16.5% of those with multi-VRI involving LAD, and 7.3% of patients with multi-VRI not involving LAD (overall P < .001). Even at incremental multivariable Cox proportional analysis, hierarchical VRI was independently associated with an increased risk of D/MI [hazard ratio = 1.17 (1.04-1.08) for each class increment, P = .010]. Location and extent of myocardial ischemia at MPS according to the VRI concept have a hierarchical predictive impact, with multi-VRI involving LAD being significantly and independently more prognostically ominous than other types of VRI.

Longitudinal study of prognostic factors in established periodontitis patients.

PubMed

Machtei, E E; Dunford, R; Hausmann, E; Grossi, S G; Powell, J; Cummins, D; Zambon, J J; Genco, R J

1997-02-01

Numerous indicators for disease progression have been described in the last decade. The purpose of this study was to examine, longitudinally, a large battery of clinical, microbiological, and immunological indicators, to try to determine whether the presence of one or a combination of these parameters at baseline, would correlate positively with increased attachment and or bone loss (true prognostic factors). Following initial screening, 79 patients with established periodontitis were monitored longitudinally for one year. Whole mouth clinical measurements, plaque gingival and calculus indices, together with pocket depth and attachment level measurements, were repeated every three months. Full mouth radiographic survey, performed at baseline and 12 months, served to determine changes in crestal bone height using an image enhancement technique. Subgingival plaque samples were taken at baseline and every 3 months. Immunofluorescence assays were performed for the a battery of target microorganisms. Serum and GCF samples for IgG subclasses analysis were obtained at each visit and assayed using ELISA techniques. Likewise blood, samples were also drawn at each visit for a quantitative analysis of serum cotinine level. The overall mean attachment loss (AL) and bone loss (BL) were almost identical (0.159 mm and 0.164 mm, respectively). Individual patients variation was large (-0.733 to +1.004 mm). An overall 6.89% of sites were active; individual patients' means ranged from 0-28.9%. Mean pocket depth (PD) showed minimal change over the study period (-0.033 mm) thus suggesting that most if not all the AL was accompained by concomitant gingival recession. Smokers exhibited greater AL and radiographic BL compared to non-smokers. Likewise, patients' cotinine level showed direct correlation with outcomes of progressive periodontal breakdown. Past severity of periodontal involvement, as reflected in the patients baseline PD, AL and crestal bone height, showed good correlation with longitudinal changes in the periodontium. This correlation was higher for crestal BL as the outcome variable, while somewhat smaller for change in AL as the outcome variable. Bacteroides forsythus (Bf.), Prevotella intermedia (Pi.) and Porphyromonas gingivalis (Pg.) were frequently found in these patients. The presence of these microorganisms at baseline was associated with further disease progression. Subjects with mean baseline pocket depth equal or greater than 3.2 mm were at greater risk for future bone loss 1 year later (O.R. 2.97; C.I. 1.02-8.70). Smokers were at significantly greater risk for further attachment loss when compared to non-smokers (O.R. 5.41; C.I. 1.50-19.5). Subjects that harbored B. forsythus at baseline, were at seven times greater risk for increased pocket depth (O.R. 7.84; C.I.1.74-35.3). In conclusion, past periodontal destruction, smoking habits, Bf., Pg., & Pi. are prognostic factors for further periodontal breakdown. When designing clinical trials, or when evaluating epidemiological data, it is most important to balance for these factors. Also, treatment strategies should attempt to eliminate or modify these factors.

Preoperative Recipient Parameters Allow Early Estimation of Postoperative Outcome and Intraoperative Transfusion Requirements in Liver Transplantation.

PubMed

Schumacher, Carsten; Eismann, Hendrik; Sieg, Lion; Friedrich, Lars; Scheinichen, Dirk; Vondran, Florian W R; Johanning, Kai

2018-01-01

Liver transplantation is a complex intervention, and early anticipation of personnel and logistic requirements is of great importance. Early identification of high-risk patients could prove useful. We therefore evaluated prognostic values of recipient parameters commonly available in the early preoperative stage regarding postoperative 30- and 90-day outcomes and intraoperative transfusion requirements in liver transplantation. All adult patients undergoing first liver transplantation at Hannover Medical School between January 2005 and December 2010 were included in this retrospective study. Demographic, clinical, and laboratory data as well as clinical courses were recorded. Prognostic values regarding 30- and 90-day outcomes were evaluated by uni- and multivariate statistical tests. Identified risk parameters were used to calculate risk scores. There were 426 patients (40.4% female) included with a mean age of 48.6 (11.9) years. Absolute 30-day mortality rate was 9.9%, and absolute 90-day mortality rate was 13.4%. Preoperative leukocyte count >5200/μL, platelet count <91 000/μL, and creatinine values ≥77 μmol/L were relevant risk factors for both observation periods ( P < .05, respectively). A score based on these factors significantly differentiated between groups of varying postoperative outcomes and intraoperative transfusion requirements ( P < .05, respectively). A score based on preoperative creatinine, leukocyte, and platelet values allowed early estimation of postoperative 30- and 90-day outcomes and intraoperative transfusion requirements in liver transplantation. Results might help to improve timely logistic and personal strategies.

Lungscape: resected non-small-cell lung cancer outcome by clinical and pathological parameters.

PubMed

Peters, Solange; Weder, Walter; Dafni, Urania; Kerr, Keith M; Bubendorf, Lukas; Meldgaard, Peter; O'Byrne, Kenneth J; Wrona, Anna; Vansteenkiste, Johan; Felip, Enriqueta; Marchetti, Antonio; Savic, Spasenija; Lu, Shun; Smit, Egbert; Dingemans, Anne-Marie; Blackhall, Fiona H; Baas, Paul; Camps, Carlos; Rosell, Rafael; Stahel, Rolf A

2014-11-01

The Lungscape project was designed to address the impact of clinical, pathological, and molecular characteristics on outcome in resected non-small- cell lung cancer (NSCLC). A decentralized biobank with fully annotated tissue samples was established. Selection criteria for participating centers included sufficient number of cases, tissue microarray building capability, and documented ethical approval. Patient selection was based on availability of comprehensive clinical data, radical resection between 2003 and 2009 with adequate follow-up, and adequate quantity and quality of formalin-fixed tissue. Fifteen centers contributed 2449 cases. The 5-year overall survival (OS) was 69.6% and 63.6% for stages IA and IB, 51.6% and 47.7% for stages IIA and IIB, and 29.0% and 13.0% for stages IIIA and IIIB, respectively (p < 0.001). Median and 5-year relapse-free survival (RFS) were 52.8 months and 47.3%, respectively. Distant relapse was recorded for 44.4%, local for 26.0%, and both for 16.9% of patients. Based on multivariate analysis for the OS, RFS, and time to relapse, the factors significantly associated with all of them are performance status and pathological stage. The aim of this report is to present the results from Lungscape, the first large series reporting on NSCLC surgical outcome measured not only by OS but also by RFS and time to relapse and including multivariate analysis by significant clinical and pathological prognostic parameters. As tissue from all patients is preserved locally and is available for detailed molecular investigations, Lungscape provides an excellent basis to evaluate the influence of molecular parameters on the disease outcome after radical resection, besides providing an overview of the molecular landscape of stage I to III NSCLC.

The genomic landscape of chronic lymphocytic leukaemia: biological and clinical implications.

PubMed

Strefford, Jonathan C

2015-04-01

Chronic lymphocytic leukaemia (CLL) remains at the forefront of the genetic analysis of human tumours, principally due its prevalence, protracted natural history and accessibility to suitable material for analysis. With the application of high-throughput genetic technologies, we have an unbridled view of the architecture of the CLL genome, including a comprehensive description of the copy number and mutational landscape of the disease, a detailed picture of clonal evolution during pathogenesis, and the molecular mechanisms that drive genomic instability and therapeutic resistance. This work has nuanced the prognostic importance of established copy number alterations, and identified novel prognostically relevant gene mutations that function within biological pathways that are attractive treatment targets. Herein, an overview of recent genomic discoveries will be reviewed, with associated biological and clinical implications, and a view into how clinical implementation may be facilitated. © 2014 John Wiley & Sons Ltd.

Diagnostic and prognostic value of cardiovascular magnetic resonance in non-ischaemic cardiomyopathies

PubMed Central

2012-01-01

Cardiovascular Magnetic Resonance (CMR) is recognised as a valuable clinical tool which in a single scan setting can assess ventricular volumes and function, myocardial fibrosis, iron loading, flow quantification, tissue characterisation and myocardial perfusion imaging. The advent of CMR using extrinsic and intrinsic contrast-enhanced protocols for tissue characterisation have dramatically changed the non-invasive work-up of patients with suspected or known cardiomyopathy. Although the technique initially focused on the in vivo identification of myocardial necrosis through the late gadolinium enhancement (LGE) technique, recent work highlighted the ability of CMR to provide more detailed in vivo tissue characterisation to help establish a differential diagnosis of the underlying aetiology, to exclude an ischaemic substrate and to provide important prognostic markers. The potential application of CMR in the clinical approach of a patient with suspected non-ischaemic cardiomyopathy is discussed in this review. PMID:22857649

PubMed Central

Taran, Florin-Andrei; Schneeweiss, Andreas; Lux, Michael P.; Janni, Wolfgang; Hartkopf, Andreas D.; Nabieva, Naiba; Overkamp, Friedrich; Kolberg, Hans-Christian; Hadji, Peyman; Tesch, Hans; Wöckel, Achim; Ettl, Johannes; Lüftner, Diana; Wallwiener, Markus; Müller, Volkmar; Beckmann, Matthias W.; Belleville, Erik; Wallwiener, Diethelm; Brucker, Sara Y.; Fasching, Peter A.; Fehm, Tanja N.; Schütz, Florian

2018-01-01

This summary provides an overview of how new therapies or new aspects of established therapies relate to the latest findings. Neoadjuvant therapy, local therapy, new aspects of systemic therapy, and prognostic and predictive factors are presented. In the neoadjuvant setting, the association between pathological complete response (pCR) and prognosis is still of interest as is the identification of new molecular predictors for new therapies such as CDK4/6 inhibitors. As regards surgical treatment, the target is still to reduce the aggressiveness of surgery. To achieve this, a better understanding particularly of ductal carcinoma in situ is required. With regard to systemic therapy, more data on the best combinations and therapy sequences for existing therapies is available. Finally, the use of prognostic and predictive factors may help to avoid overtreatment and ensure that patients only receive therapies which have been shown to be effective for their specific condition and have fewer side effects. PMID:29576629

COX-2 expression and outcome in canine nasal carcinomas treated with hypofractionated radiotherapy.

PubMed

Belshaw, Z; Constantio-Casas, F; Brearley, M J; Dunning, M D; Holmes, M A; Dobson, J M

2011-06-01

The expression of cyclooxygenase isoform 2 (COX-2) in canine nasal carcinomas has been well documented. COX-2 expression has proven to be a prognostic factor in several human tumours. The aims of this study were to assess the correlation between immunohistochemical COX-2 expression and prognosis using rhinoscopic biopsies from 42 dogs with nasal carcinomas treated with hypofractionated radiotherapy, and to establish a replicable COX-2 scoring system. Ninety per cent of sections evaluated were COX-2 positive with a mean score of 6.6 (median 8.0; range 0-12). Neither COX-2 expression nor tumour type had a significant correlation with survival. There are likely to be many as yet unidentified variants which contribute to length of survival in dogs with nasal carcinomas. Immunohistochemical COX-2 expression appears unlikely to be of prognostic significance for canine nasal carcinoma. © 2010 Blackwell Publishing Ltd.

Programmed cell death 6 interacting protein (PDCD6IP) and Rabenosyn-5 (ZFYVE20) are potential urinary biomarkers for upper gastrointestinal cancer.

PubMed

Husi, Holger; Skipworth, Richard J E; Cronshaw, Andrew; Stephens, Nathan A; Wackerhage, Henning; Greig, Carolyn; Fearon, Kenneth C H; Ross, James A

2015-06-01

Cancer of the upper digestive tract (uGI) is a major contributor to cancer-related death worldwide. Due to a rise in occurrence, together with poor survival rates and a lack of diagnostic or prognostic clinical assays, there is a clear need to establish molecular biomarkers. Initial assessment was performed on urine samples from 60 control and 60 uGI cancer patients using MS to establish a peak pattern or fingerprint model, which was validated by a further set of 59 samples. We detected 86 cluster peaks by MS above frequency and detection thresholds. Statistical testing and model building resulted in a peak profiling model of five relevant peaks with 88% overall sensitivity and 91% specificity, and overall correctness of 90%. High-resolution MS of 40 samples in the 2-10 kDa range resulted in 646 identified proteins, and pattern matching identified four of the five model peaks within significant parameters, namely programmed cell death 6 interacting protein (PDCD6IP/Alix/AIP1), Rabenosyn-5 (ZFYVE20), protein S100A8, and protein S100A9, of which the first two were validated by Western blotting. We demonstrate that MS analysis of human urine can identify lead biomarker candidates in uGI cancers, which makes this technique potentially useful in defining and consolidating biomarker patterns for uGI cancer screening. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Subsonic Aircraft Safety Icing Study

NASA Technical Reports Server (NTRS)

Jones, Sharon Monica; Reveley, Mary S.; Evans, Joni K.; Barrientos, Francesca A.

2008-01-01

NASA's Integrated Resilient Aircraft Control (IRAC) Project is one of four projects within the agency s Aviation Safety Program (AvSafe) in the Aeronautics Research Mission Directorate (ARMD). The IRAC Project, which was redesigned in the first half of 2007, conducts research to advance the state of the art in aircraft control design tools and techniques. A "Key Decision Point" was established for fiscal year 2007 with the following expected outcomes: document the most currently available statistical/prognostic data associated with icing for subsonic transport, summarize reports by subject matter experts in icing research on current knowledge of icing effects on control parameters and establish future requirements for icing research for subsonic transports including the appropriate alignment. This study contains: (1) statistical analyses of accident and incident data conducted by NASA researchers for this "Key Decision Point", (2) an examination of icing in other recent statistically based studies, (3) a summary of aviation safety priority lists that have been developed by various subject-matter experts, including the significance of aircraft icing research in these lists and (4) suggested future requirements for NASA icing research. The review of several studies by subject-matter experts was summarized into four high-priority icing research areas. Based on the Integrated Resilient Aircraft Control (IRAC) Project goals and objectives, the IRAC project was encouraged to conduct work in all of the high-priority icing research areas that were identified, with the exception of the developing of methods to sense and document actual icing conditions.

Match and mismatch - comparing plant phenological metrics from ground-observations and from a prognostic model

NASA Astrophysics Data System (ADS)

Rutishauser, This; Stöckli, Reto; Jeanneret, François; Peñuelas, Josep

2010-05-01

Changes in the seasonality of life cycles of plants as recorded in phenological observations have been widely analysed at the species level with data available for many decades back in time. At the same time, seasonality changes in satellite-based observations and prognostic phenology models comprise information at the pixel-size or landscape scale. Change analysis of satellite-based records is restricted due to relatively short satellite records that further include gaps while model-based analyses are biased due to current model deficiencies., At 30 selected sites across Europe, we analysed three different sources of plant seasonality during the 1971-2000 period. Data consisted of (1) species-specific development stages of flowering and leave-out with different species observed at each site. (2) We used a synthetic phenological metric that integrates the common interannual phenological signal across all species at one site. (3) We estimated daily Leaf Area Index with a prognostic phenology model. The prior uncertainties of the model's empirical parameter space are constrained by assimilating the Fraction of Photosynthetically Active Radiation absorbed by vegetation (FPAR) and Leaf Area Index (LAI) from the MODerate Resolution Imaging Spectroradiometer (MODIS). We extracted the day of year when the 25%, 50% and 75% thresholds were passed each spring. The question arises how the three phenological signals compare and correlate across climate zones in Europe. Is there a match between single species observations, species-based ground-observed metrics and the landscape-scale prognostic model? Are there single key-species across Europe that best represent a landscape scale measure from the prognostic model? Can one source substitute another and serve as proxy-data? What can we learn from potential mismatches? Focusing on changes in spring this contribution presents first results of an ongoing comparison study from a number of European test sites that will be extended to the pan-European phenological database Cost725 and PEP725.

Cancer classification using the Immunoscore: a worldwide task force.

PubMed

Galon, Jérôme; Pagès, Franck; Marincola, Francesco M; Angell, Helen K; Thurin, Magdalena; Lugli, Alessandro; Zlobec, Inti; Berger, Anne; Bifulco, Carlo; Botti, Gerardo; Tatangelo, Fabiana; Britten, Cedrik M; Kreiter, Sebastian; Chouchane, Lotfi; Delrio, Paolo; Arndt, Hartmann; Asslaber, Martin; Maio, Michele; Masucci, Giuseppe V; Mihm, Martin; Vidal-Vanaclocha, Fernando; Allison, James P; Gnjatic, Sacha; Hakansson, Leif; Huber, Christoph; Singh-Jasuja, Harpreet; Ottensmeier, Christian; Zwierzina, Heinz; Laghi, Luigi; Grizzi, Fabio; Ohashi, Pamela S; Shaw, Patricia A; Clarke, Blaise A; Wouters, Bradly G; Kawakami, Yutaka; Hazama, Shoichi; Okuno, Kiyotaka; Wang, Ena; O'Donnell-Tormey, Jill; Lagorce, Christine; Pawelec, Graham; Nishimura, Michael I; Hawkins, Robert; Lapointe, Réjean; Lundqvist, Andreas; Khleif, Samir N; Ogino, Shuji; Gibbs, Peter; Waring, Paul; Sato, Noriyuki; Torigoe, Toshihiko; Itoh, Kyogo; Patel, Prabhu S; Shukla, Shilin N; Palmqvist, Richard; Nagtegaal, Iris D; Wang, Yili; D'Arrigo, Corrado; Kopetz, Scott; Sinicrope, Frank A; Trinchieri, Giorgio; Gajewski, Thomas F; Ascierto, Paolo A; Fox, Bernard A

2012-10-03

Prediction of clinical outcome in cancer is usually achieved by histopathological evaluation of tissue samples obtained during surgical resection of the primary tumor. Traditional tumor staging (AJCC/UICC-TNM classification) summarizes data on tumor burden (T), presence of cancer cells in draining and regional lymph nodes (N) and evidence for metastases (M). However, it is now recognized that clinical outcome can significantly vary among patients within the same stage. The current classification provides limited prognostic information, and does not predict response to therapy. Recent literature has alluded to the importance of the host immune system in controlling tumor progression. Thus, evidence supports the notion to include immunological biomarkers, implemented as a tool for the prediction of prognosis and response to therapy. Accumulating data, collected from large cohorts of human cancers, has demonstrated the impact of immune-classification, which has a prognostic value that may add to the significance of the AJCC/UICC TNM-classification. It is therefore imperative to begin to incorporate the 'Immunoscore' into traditional classification, thus providing an essential prognostic and potentially predictive tool. Introduction of this parameter as a biomarker to classify cancers, as part of routine diagnostic and prognostic assessment of tumors, will facilitate clinical decision-making including rational stratification of patient treatment. Equally, the inherent complexity of quantitative immunohistochemistry, in conjunction with protocol variation across laboratories, analysis of different immune cell types, inconsistent region selection criteria, and variable ways to quantify immune infiltration, all underline the urgent requirement to reach assay harmonization. In an effort to promote the Immunoscore in routine clinical settings, an international task force was initiated. This review represents a follow-up of the announcement of this initiative, and of the J Transl Med. editorial from January 2012. Immunophenotyping of tumors may provide crucial novel prognostic information. The results of this international validation may result in the implementation of the Immunoscore as a new component for the classification of cancer, designated TNM-I (TNM-Immune).

A nationwide multi-institutional retrospective study to identify prognostic factors and develop a graded prognostic assessment system for patients with brain metastases from uterine corpus and cervical cancer.

PubMed

Hayashi, Nakamasa; Takahashi, Hideaki; Hasegawa, Yuzo; Higuchi, Fumi; Takahashi, Masamichi; Makino, Keishi; Takagaki, Masatoshi; Akimoto, Jiro; Okuda, Takeshi; Okita, Yoshiko; Mitsuya, Koichi; Hirashima, Yasuyuki; Narita, Yoshitaka; Nakasu, Yoko

2017-06-02

The prevalence of brain metastases (BM) from uterine cancer has recently increased because of the improvement of overall survival (OS) of patients with uterine cancer due to its early detection and improved local control as a result of new effective treatments. However, little information is available regarding their clinical characteristics and prognosis, because oncologists have encountered BM from uterine cancer on rare occasions. Records from 81 patients with uterine BM were collected from 10 institutes in Japan. These were used in a multi-institutional study to identify prognostic factors and develop a graded prognostic assessment (GPA) for patients with BM from uterine cancer. Median OS after the development of BM was 7 months (95% confidence interval, 4 to 10 months). Multivariate analysis revealed that there were survival differences according to the existence of extracranial metastases and number of BM. In the present uterine-GPA, a score of 0 was assigned to those patients with ≥5 BM and extracranial metastasis, a score of 2 was assigned to those patients with one to four BM or without extracranial metastasis, and a score of 4 was assigned to those patients with one to four BM and without extracranial metastasis. The median OS for patients with a uterine-GPA scores of 0, 2, and 4 was 3, 7, and 22 months, respectively. A survival analysis confirmed the presence of statistically significant differences between these groups (p < 0.05). The results were validated by data obtained from the National Report of Brain Tumor Registry of Japan. Uterine GPA incorporates two simple clinical parameters of high prognostic significance and can be used to predict the expected survival times in patients with BM from uterine cancer. Its use may help in determining an appropriate treatment for individual patients with BM.

Prognostic factors for ovarian epithelial cancer in the elderly: a case-control study.

PubMed

Sabatier, Renaud; Calderon, Benoît; Lambaudie, Eric; Chereau, Elisabeth; Provansal, Magali; Cappiello, Maria-Antonietta; Viens, Patrice; Rousseau, Frederique

2015-06-01

Ovarian cancer is the leading cause of mortality by gynecologic cancers in Western countries. Many publications have suggested that age may be an independent prognostic factor in ovarian carcinoma. There are only few data concerning the impact of treatments and geriatric features within the elderly population. We collected data of older (≥ 70 years old) patients treated in our institution for an invasive ovarian carcinoma between 1995 and 2011. First we described usual clinical and pathological features for these patients, as well as their outcome. We compared these parameters with that of young (<70 years old) patients treated during the same period. We then observed geriatric features in our set: Eastern Cooperative Oncology Group performance status, number of medications, Charlson index, body mass index, hemoglobin, and glomerular filtration rate. We finally looked for prognostic factors specific of the elderly population. One hundred nine elderly patients were identified and compared with 488 younger cases. There was no difference concerning clinicopathologic data. Surgery was more frequently complete in young women (58% vs 41.7%), and older patients received less chemotherapy courses and less taxanes (38.4% vs 67.1%). Young patients had a longer overall survival (median, 65.2 vs 26.2 months, P = 8.5E-10, log-rank test). Multivariate analyses confirmed that age was an independent prognostic factor and that within the elderly set the International Federation of Gynecology and Obstetrics stage, surgery results, number of chemotherapy cycles administered and performance status had a significant prognostic value. No clear correlation could be observed between geriatric characteristics and treatments administration. Ovarian cancer prognosis is poorer for older women, but they are more frequently suboptimally treated. No correlation could be observed between geriatric factors and surgery or chemotherapy achievement. Treatment decision should be based on objective geriatric assessment in order to improve outcome in this population.

D-Cycloserine Augmentation of Cognitive Behavioral Group Therapy of Social Anxiety Disorder: Prognostic and Prescriptive Variables

PubMed Central

Smits, Jasper A. J.; Hofmann, Stefan G.; Rosenfield, David; DeBoer, Lindsey B.; Costa, Paul T.; Simon, Naomi M.; O'Cleirigh, Conall; Meuret, Alicia E.; Marques, Luana; Otto, Michael W.; Pollack, Mark H.

2014-01-01

Objective The aim of the current study was to identify individual characteristics that (1) predict symptom improvement with group cognitive behavioral therapy (CBT) for social anxiety disorder (SAD; i.e., prognostic variables) or (2) moderate the effects of d-cycloserine vs. placebo augmentation of CBT for SAD (i.e., prescriptive variables). Method Adults with SAD (N=169) provided Liebowitz Social Anxiety Scale (LSAS) scores in a trial evaluating DCS augmentation of group CBT. Rate of symptom improvement during therapy and posttreatment symptom severity were evaluated using multilevel modeling. As predictors of these two parameters, we selected the range of variables assessed at baseline (demographic characteristics, clinical characteristics, personality traits). Using step-wise analyses, we first identified prognostic and prescriptive variables within each of these domains and then entered these significant predictors simultaneously in one final model. Results African American ethnicity and cohabitation status were associated with greater overall rates of improvement during therapy and lower posttreatment severity. Higher initial severity was associated with a greater improvement during therapy, but also higher posttreatment severity (the greater improvement was not enough to overcome the initial higher severity). D-cycloserine augmentation was evident only among individuals low in conscientiousness and high in agreeableness. Conclusions African American ethnicity, cohabitation status, and initial severity are prognostic of favorable CBT outcomes in SAD. D-cycloserine augmentation appears particularly useful for patients low in conscientiousness and high in agreeableness. These findings can guide clinicians in making decisions about treatment strategies and can help direct research on the mechanisms of these treatments. PMID:23937345

Prognostic value of 18F-FDG-PET/CT in patients with nasopharyngeal carcinoma: a systematic review and meta-analysis.

PubMed

Lin, Jie; Xie, Guozhu; Liao, Guixiang; Wang, Baiyao; Yan, Miaohong; Li, Hui; Yuan, Yawei

2017-05-16

The prognostic role of 18F-fluorodeoxyglucose positron emission tomography CT (18F-FDG PET/CT) parameters is still controversial in nasopharyngeal carcinoma patients. We sought to perform a systematic review and meta-analysis to explore the prognostic value of maximal standardized uptake value (SUVmax), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) on event-free survival (EFS) and overall survival (OS) in nasopharyngeal carcinoma patients. Fifteen studies comprising 1,938 patients were included in this study. The combined hazard ratios (HRs) for EFS were 2.63 (95%CI 1.71-4.05) for SUVmax, 2.55 (95%CI 1.49-4.35) for MTV, and 3.32 (95%CI 1.23-8.95) for TLG. The pooled HRs for OS were 2.07 (95%CI 1.54-2.79) for SUVmax, 3.86 (95%CI 1.85-8.06) for MTV, and 2.60 (95%CI 1.55-4.34) for TLG. The prognostic role of SUVmax, MTV and TLG remained similar in the sub-group analyses. A systematic literature search was performed to identify studies which associated 18F-FDG PET/CT to clinical survival outcomes of nasopharyngeal carcinoma patients. The summarized HRs for EFS and OS were estimated by using fixed- or random-effect models according to heterogeneity between trials. The present meta-analysis confirms that high values of SUVmax, MTV and TLG predicted a higher risk of adverse events or death in patients with nasopharyngeal carcinoma, despite clinically heterogeneous nasopharyngeal carcinoma patients and the various methods adopted between these studies.

Influence of phenotype at diagnosis and of other potential prognostic factors on the course of inflammatory bowel disease.

PubMed

Romberg-Camps, M J L; Dagnelie, P C; Kester, A D M; Hesselink-van de Kruijs, M A M; Cilissen, M; Engels, L G J B; Van Deursen, C; Hameeteman, W H A; Wolters, F L; Russel, M G V M; Stockbrügger, R W

2009-02-01

Disease course in inflammatory bowel disease (IBD) is variable and difficult to predict. To optimize prognosis, it is of interest to identify phenotypic characteristics at disease onset and other prognostic factors that predict disease course. The aim of this study was to evaluate such factors in a population-based IBD group. IBD patients diagnosed between 1 January 1991 and 1 January 2003 were included. A follow-up questionnaire was developed and medical records were reviewed. Patients were classified according to phenotype at diagnosis and risk factors were registered. Disease severity, cumulative medication use, and "surgical" and "nonsurgical" recurrence rates were calculated as outcome parameters. In total, 476 Crohn's disease (CD), 630 ulcerative colitis (UC), and 81 indeterminate colitis (IC) patients were diagnosed. In CD (mean follow-up 7.6 years), 50% had undergone resective surgery. In UC (mean follow-up 7 years), colectomy rate was 8.3%. First year cumulative recurrence rates per 100 patient-years for CD, UC, and IC were 53, 44, and 42%, respectively. In CD, small bowel localization and stricturing disease were negative prognostic factors for surgery, as was young age. Overall recurrence rate was increased by young age and current smoking. In UC, extensive colitis increased surgical risk. In UC, older age at diagnosis initially increased recurrence risk but was subsequently protective. This population-based IBD study showed high recurrence rates in the first year. In CD, small bowel localization, stricturing disease, and young age were predictive for disease recurrence. In UC, extensive colitis and older age at diagnosis were negative prognostic predictors.

Factors affecting mortality in elderly patients who underwent surgery for gastric cancer.

PubMed

Kayılıoglu, Selami Ilgaz; Göktug, Ufuk Utku; Dinc, Tolga; Sozen, Isa; Yavuz, Zeynep; Coskun, Faruk

2018-03-05

The aim of this study was to determine factors affecting overall mortality in patients over 60 years of age who underwent surgery for gastric cancer in our clinic. Data on histopathological diagnosis (tumor size, lymph node status, and number), pathological stage, serum albumin level, tumor markers, complete blood count, and demographic information of 109 patients over 60 years of age who had surgery for gastric cancer between January 2011 and July 2016 were obtained retrospectively from the patient files. In addition, the survival status of all patients were examined and recorded. Metastatic lymph node ratio (MLR), red cell distribution width platelet ratio (RPR), neutrophil-lymphocyte ratio (NLR), plateletlymphocyte ratio (PLR), and prognostic nutritional index (PNI) were calculated. On univariate analysis of independent parameters, pathological LN number (p = 0.001), MLR (p <0.001), T3 (p = 0.001) or T4 (p = 0,006) tumor stage according to TNM system, the presence of metastasis (p = 0.063), and male gender (p = 0.066) were found to affect overall mortality (OM). On multivariable Cox regression analysis of these results, MLR (p = 0.005) and T stage (p = 0.006) was determined to be a statistically significant and independent prognostic value. In patients over 60 years of age who underwent surgery for gastric cancer, the factors affecting mortality were determined to be the presence of metastases, number of pathological lymph nodes, and male gender. Metastatic lymph node ratio and T1&T2 stage were determined to be independent prognostic factors. Elderly, Gastric cancer, Mortality, Prognostic factor.

Proposal and validation of a new model to estimate survival for hepatocellular carcinoma patients.

PubMed

Liu, Po-Hong; Hsu, Chia-Yang; Hsia, Cheng-Yuan; Lee, Yun-Hsuan; Huang, Yi-Hsiang; Su, Chien-Wei; Lee, Fa-Yauh; Lin, Han-Chieh; Huo, Teh-Ia

2016-08-01

The survival of hepatocellular carcinoma (HCC) patients is heterogeneous. We aim to develop and validate a simple prognostic model to estimate survival for HCC patients (MESH score). A total of 3182 patients were randomised into derivation and validation cohort. Multivariate analysis was used to identify independent predictors of survival in the derivation cohort. The validation cohort was employed to examine the prognostic capabilities. The MESH score allocated 1 point for each of the following parameters: large tumour (beyond Milan criteria), presence of vascular invasion or metastasis, Child-Turcotte-Pugh score ≥6, performance status ≥2, serum alpha-fetoprotein level ≥20 ng/ml, and serum alkaline phosphatase ≥200 IU/L, with a maximal of 6 points. In the validation cohort, significant survival differences were found across all MESH scores from 0 to 6 (all p < 0.01). The MESH system was associated with the highest homogeneity and lowest corrected Akaike information criterion compared with Barcelona Clínic Liver Cancer, Hong Kong Liver Cancer (HKLC), Cancer of the Liver Italian Program, Taipei Integrated Scoring and model to estimate survival in ambulatory HCC Patients systems. The prognostic accuracy of the MESH scores remained constant in patients with hepatitis B- or hepatitis C-related HCC. The MESH score can also discriminate survival for patients from early to advanced stages of HCC. This newly proposed simple and accurate survival model provides enhanced prognostic accuracy for HCC. The MESH system is a useful supplement to the BCLC and HKLC classification schemes in refining treatment strategies. Copyright © 2016 Elsevier Ltd. All rights reserved.

Prognostic impact of alternative splicing-derived hMENA isoforms in resected, node-negative, non-small-cell lung cancer

PubMed Central

Sperduti, Isabella; Iapicca, Pierluigi; Visca, Paolo; Alessandrini, Gabriele; Antoniani, Barbara; Pilotto, Sara; Ludovini, Vienna; Vannucci, Jacopo; Bellezza, Guido; Sidoni, Angelo; Tortora, Giampaolo; Radisky, Derek C.; Crinò, Lucio; Cognetti, Francesco; Facciolo, Francesco; Mottolese, Marcella

2014-01-01

Risk assessment and treatment choice remain a challenge in early non-small-cell lung cancer (NSCLC). Alternative splicing is an emerging source for diagnostic, prognostic and therapeutic tools. Here, we investigated the prognostic value of the actin cytoskeleton regulator hMENA and its isoforms, hMENA11a and hMENAΔv6, in early NSCLC. The epithelial hMENA11a isoform was expressed in NSCLC lines expressing E-CADHERIN and was alternatively expressed with hMENAΔv6. Enforced expression of hMENAΔv6 or hMENA11a increased or decreased the invasive ability of A549 cells, respectively. hMENA isoform expression was evaluated in 248 node-negative NSCLC. High pan-hMENA and low hMENA11a were the only independent predictors of shorter disease-free and cancer-specific survival, and low hMENA11a was an independent predictor of shorter overall survival, at multivariate analysis. Patients with low pan-hMENA/high hMENA11a expression fared significantly better (P≤0.0015) than any other subgroup. Such hybrid variable was incorporated with T-size and number of resected lymph nodes into a 3-class-risk stratification model, which strikingly discriminated between different risks of relapse, cancer-related death, and death. The model was externally validated in an independent dataset of 133 patients. Relative expression of hMENA splice isoforms is a powerful prognostic factor in early NSCLC, complementing clinical parameters to accurately predict individual patient risk. PMID:25373410

CXCL12 promoter methylation and PD-L1 expression as prognostic biomarkers in prostate cancer patients.

PubMed

Goltz, Diane; Holmes, Emily Eva; Gevensleben, Heidrun; Sailer, Verena; Dietrich, Jörn; Jung, Maria; Röhler, Magda; Meller, Sebastian; Ellinger, Jörg; Kristiansen, Glen; Dietrich, Dimo

2016-08-16

The CXCR4/CXCL12 axis plays a central role in systemic metastasis of prostate carcinoma (PCa), thereby representing a promising target for future therapies. Recent data suggest that the CXCR4/CXCL12 axis is functionally linked to the PD-1/PD-L1 immune checkpoint. We evaluated the prognostic value of aberrant CXCL12 DNA methylation with respect to PD-L1 expression in primary PCa. CXCL12 methylation showed a consistent significant correlation with Gleason grading groups in both cohorts (p < 0.001 for training and p = 0.034 for testing cohort). Short BCR-free survival was significantly associated with aberrant CXCL12 methylation in both cohorts and served as an independent prognostic factor in the testing cohort (hazard ratio = 1.92 [95%CI: 1.12-3.27], p = 0.049). Concomitant aberrant CXCL12 methylation and high PD-L1 expression was significantly associated with shorter BCR-free survival (p = 0.005). In comparative analysis, the CXCL12 methylation assay was able to provide approximately equivalent results in biopsy and prostatectomy specimens. CXCL12 methylation was determined by means of a methylation specific quantitative PCR analysis in a radical prostatectomy patient cohort (n = 247, training cohort). Data published by The Cancer Genome Atlas served as a testing cohort (n = 498). CXCL12 methylation results were correlated to clinicopathological parameters including biochemical recurrence (BCR)-free survival. CXCL12 methylation is a powerful prognostic biomarker for BCR in PCa patients after radical prostatectomy. Further studies need to ascertain if CXCL12 methylation may aid in planning active surveillance strategies.

Single Plant Root System Modeling under Soil Moisture Variation

NASA Astrophysics Data System (ADS)

Yabusaki, S.; Fang, Y.; Chen, X.; Scheibe, T. D.

2016-12-01

A prognostic Virtual Plant-Atmosphere-Soil System (vPASS) model is being developed that integrates comprehensively detailed mechanistic single plant modeling with microbial, atmospheric, and soil system processes in its immediate environment. Three broad areas of process module development are targeted: Incorporating models for root growth and function, rhizosphere interactions with bacteria and other organisms, litter decomposition and soil respiration into established porous media flow and reactive transport models Incorporating root/shoot transport, growth, photosynthesis and carbon allocation process models into an integrated plant physiology model Incorporating transpiration, Volatile Organic Compounds (VOC) emission, particulate deposition and local atmospheric processes into a coupled plant/atmosphere model. The integrated plant ecosystem simulation capability is being developed as open source process modules and associated interfaces under a modeling framework. The initial focus addresses the coupling of root growth, vascular transport system, and soil under drought scenarios. Two types of root water uptake modeling approaches are tested: continuous root distribution and constitutive root system architecture. The continuous root distribution models are based on spatially averaged root development process parameters, which are relatively straightforward to accommodate in the continuum soil flow and reactive transport module. Conversely, the constitutive root system architecture models use root growth rates, root growth direction, and root branching to evolve explicit root geometries. The branching topologies require more complex data structures and additional input parameters. Preliminary results are presented for root model development and the vascular response to temporal and spatial variations in soil conditions.

Oxygen regulates amino acid turnover and carbohydrate uptake during the preimplantation period of mouse embryo development.

PubMed

Wale, Petra L; Gardner, David K

2012-07-01

Oxygen is a powerful regulator of preimplantation embryo development, affecting gene expression, the proteome, and energy metabolism. Even a transient exposure to atmospheric oxygen can have a negative impact on embryo development, which is greatest prior to compaction, and subsequent postcompaction culture at low oxygen cannot alleviate this damage. In spite of this evidence, the majority of human in vitro fertilization is still performed at atmospheric oxygen. One of the physiological parameters shown to be affected by the relative oxygen concentration, carbohydrate metabolism, is linked to the ability of the mammalian embryo to develop in culture and remain viable after transfer. The aim of this study was, therefore, to determine the effect of oxygen concentration on the ability of mouse embryos to utilize both amino acids and carbohydrates both before and after compaction. Metabolomic and fluorometric analysis of embryo culture media revealed that when embryos were exposed to atmospheric oxygen during the cleavage stages, they exhibited significantly greater amino acid utilization and pyruvate uptake than when cultured under 5% oxygen. In contrast, postcompaction embryos cultured in atmospheric oxygen showed significantly lower mean amino acid utilization and glucose uptake. These metabolic changes correlated with developmental compromise because embryos grown in atmospheric oxygen at all stages showed significantly lower blastocyst formation and proliferation. These findings confirm the need to consider both embryo development and metabolism in establishing optimal human embryo growth conditions and prognostic markers of viability, and further highlight the impact of oxygen on such vital parameters.

Biomarkers For Breast Cancer Based On Genetic Instability | NCI Technology Transfer Center | TTC

Cancer.gov

It is difficult to establish a prognosis for breast cancer because the clinical course and survival times of patients with the disease vary greatly.  The National Cancer Institute's Genetics Branch is seeking statements of capability or interest from parties interested in in-licensing or collaborative research to co-develop, evaluate, or commercialize prognostic tests for breast cancer based on a 12-gene expression signature.

An Evidence-Based Approach to the Assessment of Heart-Type Fatty Acid Binding Protein in Acute Coronary Syndrome

PubMed Central

Viswanathan, Karthik; Hall, Alistair S; Barth, Julian H

2012-01-01

Cardiac troponins have been the biomarkers of choice for the diagnosis of acute coronary syndrome (ACS) for over a decade. There has, however, been considerable interest over the last two decades for newer biomarkers that would bring added value to the measurement of troponin such as the provision of prognosis and assistance in the choice of therapeutic interventions. In this manuscript, we review the development of heart-type fatty acid binding protein (H-FABP) in patients with ACS using the evidence-based laboratory medicine format. Phase I studies have established that H-FABP reference intervals and pre-analytical factors influencing H-FABP. Phase II studies have confirmed a) that H-FABP is elevated in patients with established myocardial infarction; b) that its serum concentration is related to the extent of infarction using survival as a surrogate; and c) that its use in chest pain patients can identify ACS patients and also provide prognostic information on survival. Furthermore, it is an independent prognostic marker for patients with suspected ACS who are troponin negative. Phase III studies involving randomised control trials for diagnosis and prognosis have not yet been performed and Phase IV studies await uptake of H-FABP in a routine service. PMID:22363093

Associations of circulating plasma microRNAs with age, body mass index and sex in a population-based study.

PubMed

Ameling, Sabine; Kacprowski, Tim; Chilukoti, Ravi Kumar; Malsch, Carolin; Liebscher, Volkmar; Suhre, Karsten; Pietzner, Maik; Friedrich, Nele; Homuth, Georg; Hammer, Elke; Völker, Uwe

2015-10-14

Non-cellular blood circulating microRNAs (plasma miRNAs) represent a promising source for the development of prognostic and diagnostic tools owing to their minimally invasive sampling, high stability, and simple quantification by standard techniques such as RT-qPCR. So far, the majority of association studies involving plasma miRNAs were disease-specific case-control analyses. In contrast, in the present study, plasma miRNAs were analysed in a sample of 372 individuals from a population-based cohort study, the Study of Health in Pomerania (SHIP). Quantification of miRNA levels was performed by RT-qPCR using the Exiqon Serum/Plasma Focus microRNA PCR Panel V3.M covering 179 different miRNAs. Of these, 155 were included in our analyses after quality-control. Associations between plasma miRNAs and the phenotypes age, body mass index (BMI), and sex were assessed via a two-step linear regression approach per miRNA. The first step regressed out the technical parameters and the second step determined the remaining associations between the respective plasma miRNA and the phenotypes of interest. After regressing out technical parameters and adjusting for the respective other two phenotypes, 7, 15, and 35 plasma miRNAs were significantly (q < 0.05) associated with age, BMI, and sex, respectively. Additional adjustment for the blood cell parameters identified 12 and 19 miRNAs to be significantly associated with age and BMI, respectively. Most of the BMI-associated miRNAs likely originate from liver. Sex-associated differences in miRNA levels were largely determined by differences in blood cell parameters. Thus, only 7 as compared to originally 35 sex-associated miRNAs displayed sex-specific differences after adjustment for blood cell parameters. These findings emphasize that circulating miRNAs are strongly impacted by age, BMI, and sex. Hence, these parameters should be considered as covariates in association studies based on plasma miRNA levels. The established experimental and computational workflow can now be used in future screening studies to determine associations of plasma miRNAs with defined disease phenotypes.

Expression of autophagy-related protein beclin-1 in malignant canine mammary tumors

PubMed Central

2013-01-01

Background Autophagy is a self-catabolic mechanism that degrades unnecessary cellular components through lysosomal enzymes. Beclin-1, an autophagy-related protein, establishes the first connection between autophagy and tumorigenesis. The purpose of this study is to assess the Beclin-1 expression pattern and to determine its prognostic significance in patients with malignant canine mammary tumor (CMT). Results We examined Beclin-1 expression in 70 cases of malignant CMTs by immunohistochemistry. Cytoplasmic Beclin-1 expression was significantly weaker in cancer cells than in nearby normal mammary glands (p < 0.001). Low cytoplasmic expression (57.14%) was associated with older age, lower degree of tubular formation, increased mitotic activity, higher histologic grade, and extensive necrosis. Low nuclear expression (40%) was connected with older age, lower degree of tubular formation, extensive necrosis, and negative for Her2/neu overexpression. Univariate survival analysis showed that Beclin-1 cytoplasmic expression was a poor prognostic factor for overall survival rate (p < 0.001). Multivariate survival analysis demonstrated that Beclin-1 cytoplasmic expression is an independent prognostic factor (p = 0.016). Conclusions Loss of Beclin-1 is associated with aggressive clinicopathologic features and poor overall survival. The results suggest that Beclin-1 plays an important role in tumor progression of malignant CMTs. PMID:23578251

Promising System for Selecting Healthy In Vitro–Fertilized Embryos in Cattle

PubMed Central

Sugimura, Satoshi; Akai, Tomonori; Hashiyada, Yutaka; Somfai, Tamás; Inaba, Yasushi; Hirayama, Muneyuki; Yamanouchi, Tadayuki; Matsuda, Hideo; Kobayashi, Shuji; Aikawa, Yoshio; Ohtake, Masaki; Kobayashi, Eiji; Konishi, Kazuyuki; Imai, Kei

2012-01-01

Conventionally, in vitro–fertilized (IVF) bovine embryos are morphologically evaluated at the time of embryo transfer to select those that are likely to establish a pregnancy. This method is, however, subjective and results in unreliable selection. Here we describe a novel selection system for IVF bovine blastocysts for transfer that traces the development of individual embryos with time-lapse cinematography in our developed microwell culture dish and analyzes embryonic metabolism. The system can noninvasively identify prognostic factors that reflect not only blastocyst qualities detected with histological, cytogenetic, and molecular analysis but also viability after transfer. By assessing a combination of identified prognostic factors—(i) timing of the first cleavage; (ii) number of blastomeres at the end of the first cleavage; (iii) presence or absence of multiple fragments at the end of the first cleavage; (iv) number of blastomeres at the onset of lag-phase, which results in temporary developmental arrest during the fourth or fifth cell cycle; and (v) oxygen consumption at the blastocyst stage—pregnancy success could be accurately predicted (78.9%). The conventional method or individual prognostic factors could not accurately predict pregnancy. No newborn calves showed neonatal overgrowth or death. Our results demonstrate that these five predictors and our system could provide objective and reliable selection of healthy IVF bovine embryos. PMID:22590579

Discrimination measures for survival outcomes: connection between the AUC and the predictiveness curve.

PubMed

Viallon, Vivian; Latouche, Aurélien

2011-03-01

Finding out biomarkers and building risk scores to predict the occurrence of survival outcomes is a major concern of clinical epidemiology, and so is the evaluation of prognostic models. In this paper, we are concerned with the estimation of the time-dependent AUC--area under the receiver-operating curve--which naturally extends standard AUC to the setting of survival outcomes and enables to evaluate the discriminative power of prognostic models. We establish a simple and useful relation between the predictiveness curve and the time-dependent AUC--AUC(t). This relation confirms that the predictiveness curve is the key concept for evaluating calibration and discrimination of prognostic models. It also highlights that accurate estimates of the conditional absolute risk function should yield accurate estimates for AUC(t). From this observation, we derive several estimators for AUC(t) relying on distinct estimators of the conditional absolute risk function. An empirical study was conducted to compare our estimators with the existing ones and assess the effect of model misspecification--when estimating the conditional absolute risk function--on the AUC(t) estimation. We further illustrate the methodology on the Mayo PBC and the VA lung cancer data sets. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The potential use of primary human upper urinary tract urothelial cell carcinoma (UUT-UCC) cultured cells for prognostic indicators and chemosensitivity test.

PubMed

Hsieh, Teng-Fu; Chen, Chi-Cheng; Chang, Chao-Hsiang; Yu, Ai-Lin; Ma, Wen-Lung; Shyr, Chih-Rong

2013-07-01

Upper urinary tract urothelial cell carcinoma (UUT-UCC) is a rare yet aggressive urologic tumor with a high rate of recurrence and metastasis, resulting in high mortality. Chemotherapy has been used to prevent recurrence and treat metastatic UUT-UCCs. Although UUT-UCC is sensitive to chemotherapy, the patients' responses to therapy vary and the therapy outcome is unpredictable. Therefore, the identification of patients who are at high risk of failure in chemotherapy is important for accurate prognostication, patient counseling, and better therapy. We have obtained cells from UUT-UCC tumor tissues after surgery and established individual primary cultured cell lines, which were used to evaluate E-cadherin and Ki-67 proliferation marker expression and their chemosensitivity to chemotherapeutic drugs. Differential Ki-67 expression and chemosensitivity were observed in these primary cultured cell lines, suggesting these types of UUT-UCC cell lines could provide a platform for determining prognostic makers and evaluating the efficacy of chemotherapy. In conclusion, primary cultured cell lines from individual patients will be a great tool for evaluating and determining each individual's personalized chemotherapy course and for testing and screening new chemotherapeutic agents against UUT-UCCs. Copyright © 2012 Elsevier GmbH. All rights reserved.

Estimating and communicating prognosis in advanced neurologic disease

PubMed Central

Gramling, Robert; Kelly, Adam G.

2013-01-01

Prognosis can no longer be relegated behind diagnosis and therapy in high-quality neurologic care. High-stakes decisions that patients (or their surrogates) make often rest upon perceptions and beliefs about prognosis, many of which are poorly informed. The new science of prognostication—the estimating and communication “what to expect”—is in its infancy and the evidence base to support “best practices” is lacking. We propose a framework for formulating a prediction and communicating “what to expect” with patients, families, and surrogates in the context of common neurologic illnesses. Because neurologic disease affects function as much as survival, we specifically address 2 important prognostic questions: “How long?” and “How well?” We provide a summary of prognostic information and highlight key points when tailoring a prognosis for common neurologic diseases. We discuss the challenges of managing prognostic uncertainty, balancing hope and realism, and ways to effectively engage surrogate decision-makers. We also describe what is known about the nocebo effects and the self-fulfilling prophecy when communicating prognoses. There is an urgent need to establish research and educational priorities to build a credible evidence base to support best practices, improve communication skills, and optimize decision-making. Confronting the challenges of prognosis is necessary to fulfill the promise of delivering high-quality, patient-centered care. PMID:23420894