Predictive and Prognostic Factors in Definition of Risk Groups in Endometrial Carcinoma
Sorbe, Bengt
2012-01-01
Background. The aim was to evaluate predictive and prognostic factors in a large consecutive series of endometrial carcinomas and to discuss pre- and postoperative risk groups based on these factors. Material and Methods. In a consecutive series of 4,543 endometrial carcinomas predictive and prognostic factors were analyzed with regard to recurrence rate and survival. The patients were treated with primary surgery and adjuvant radiotherapy. Two preoperative and three postoperative risk groups were defined. DNA ploidy was included in the definitions. Eight predictive or prognostic factors were used in multivariate analyses. Results. The overall recurrence rate of the complete series was 11.4%. Median time to relapse was 19.7 months. In a multivariate logistic regression analysis, FIGO grade, myometrial infiltration, and DNA ploidy were independent and statistically predictive factors with regard to recurrence rate. The 5-year overall survival rate was 73%. Tumor stage was the single most important factor with FIGO grade on the second place. DNA ploidy was also a significant prognostic factor. In the preoperative risk group definitions three factors were used: histology, FIGO grade, and DNA ploidy. Conclusions. DNA ploidy was an important and significant predictive and prognostic factor and should be used both in preoperative and postoperative risk group definitions. PMID:23209924
Verwoerd, A J H; Luijsterburg, P A J; Lin, C W C; Jacobs, W C H; Koes, B W; Verhagen, A P
2013-09-01
Identification of prognostic factors for surgery in patients with sciatica is important to be able to predict surgery in an early stage. Identification of prognostic factors predicting persistent pain, disability and recovery are important for better understanding of the clinical course, to inform patient and physician and support decision making. Consequently, we aimed to systematically review prognostic factors predicting outcome in non-surgically treated patients with sciatica. A search of Medline, Embase, Web of Science and Cinahl, up to March 2012 was performed for prospective cohort studies on prognostic factors for non-surgically treated sciatica. Two reviewers independently selected studies for inclusion and assessed the risk of bias. Outcomes were pain, disability, recovery and surgery. A best evidence synthesis was carried out in order to assess and summarize the data. The initial search yielded 4392 articles of which 23 articles reporting on 14 original cohorts met the inclusion criteria. High clinical, methodological and statistical heterogeneity among studies was found. Reported evidence regarding prognostic factors predicting the outcome in sciatica is limited. The majority of factors that have been evaluated, e.g., age, body mass index, smoking and sensory disturbance, showed no association with outcome. The only positive association with strong evidence was found for leg pain intensity at baseline as prognostic factor for subsequent surgery. © 2013 European Federation of International Association for the Study of Pain Chapters.
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.
Prognostic importance of DNA ploidy in non-endometrioid, high-risk endometrial carcinomas.
Sorbe, Bengt
2016-03-01
The present study investigated the predictive and prognostic impact of DNA ploidy together with other well-known prognostic factors in a series of non-endometrioid, high-risk endometrial carcinomas. From a complete consecutive series of 4,543 endometrial carcinomas of International Federation of Gynecology and Obstetrics (FIGO) stages I-IV, 94 serous carcinomas, 48 clear cell carcinomas and 231 carcinosarcomas were selected as a non-endometrioid, high-risk group for further studies regarding prognosis. The impact of DNA ploidy, as assessed by flow cytometry, was of particular focus. The age of the patients, FIGO stage, depth of myometrial infiltration and tumor expression of p53 were also included in the analyses (univariate and multivariate). In the complete series of cases, the recurrence rate was 37%, and the 5-year overall survival rate was 39% with no difference between the three histological subtypes. The primary cure rate (78%) was also similar for all tumor types studied. DNA ploidy was a significant predictive factor (on univariate analysis) for primary tumor cure rate, and a prognostic factor for survival rate (on univariate and multivariate analyses). The predictive and prognostic impact of DNA ploidy was higher in carcinosarcomas than in serous and clear cell carcinomas. In the majority of multivariate analyses, FIGO stage and depth of myometrial infiltration were the most important predictive (tumor recurrence) and prognostic (survival rate) factors. DNA ploidy status is a less important predictive and prognostic factor in non-endometrioid, high-risk endometrial carcinomas than in the common endometrioid carcinomas, in which FIGO and nuclear grade also are highly significant and important factors.
Ishikawa, Toru; Kubota, Tomoyuki; Horigome, Ryoko; Kimura, Naruhiro; Honda, Hiroki; Iwanaga, Akito; Seki, Keiichi; Honma, Terasu; Yoshida, Toshiaki
2013-01-01
The Child-Pugh classification system is the most widely used system for assessing hepatic functional reserve in HCC treatment. In the Child-Pugh classification system, serum albumin levels are used to accurately assess the status of protein metabolism and nutrition. To date, a lack of attention has been given to amino acid metabolism. In the present study, we investigated whether the branched-chain amino acids to tyrosine ratio (BTR) as an indicator of amino acid metabolism can serve as both a prognostic factor for early HCC and a predictive factor for recurrence. We conducted a cohort study of 50 patients with stage I/II HCC enrolled between May 2002 and December 2010. It was investigated whether BTR can serve as both a prognostic factor and a predictive factor for HCC recurrence. Overall survival rates were significantly higher in patients with high baseline BTR than in those with low BTR. Multivariate analysis showed that both BTR and serum albumin were prognostic factors, and that BTR was the best predictive factor for recurrence. BTR was a prognostic factor for early HCC and the most predictive factor for intrahepatic distant recurrence and contributing factors for survival.
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.
Cainap, Calin; Nagy, Viorica; Seicean, Andrada; Gherman, Alexandra; Laszlo, Istvan; Lisencu, Cosmin; Nadim, Al Hajar; Constantin, Anne-Marie; Cainap, Simona
2016-01-01
The purpose of this study was to evaluate the efficacy and toxicity of a third-generation chemotherapy regimen in the adjuvant setting to radically operated patients with gastric cancer. This proposed new adjuvant regimen was also compared with a consecutive retrospective cohort of patients treated with the classic McDonald regimen. Starting in 2006, a non-randomized prospective phase II study was conducted at the Institute of Oncology of Cluj-Napoca on 40 patients with stage IB-IV radically resected gastric adenocarcinoma. These patients were administered a chemotherapy regimen already considered to be standard treatment in the metastatic setting: ECX (epirubicin, cisplatin, xeloda) and were compared to a retrospective control group consisting of 54 patients, treated between 2001 and 2006 according to McDonald's trial. In a previous paper, we reported toxicities and the possible predictive factors for these toxicities; in the present article, we report on the results concerning predictive factors on overall survival (OS) and disease free survival (DFS). The proposed ECX treatment was not less effective than the standard suggested by McDonald's trial. Age was an independent prognostic factor in multivariate analysis. N3 stage was an independent prognostic factor for OS and DFS. N ratio >70% was an independent predictive factor for OS and locoregional disease control. The resection margins were independent prognostic factors for OS and DFS. The proposed treatment is not less effective compared with the McDonald's trial. Age was an independent prognostic factor in multivariate analysis. N3 stage represented an independent prognostic factor and N ratio >70% was a predictive factor for OS and DFS. The resection margins were proven to be independent prognostic factors for OS and DFS.
Mode of detection: an independent prognostic factor for women with breast cancer.
Hofvind, Solveig; Holen, Åsne; Román, Marta; Sebuødegård, Sofie; Puig-Vives, Montse; Akslen, Lars
2016-06-01
To investigate breast cancer survival and risk of breast cancer death by detection mode (screen-detected, interval, and detected outside the screening programme), adjusting for prognostic and predictive tumour characteristics. Information about detection mode, prognostic (age, tumour size, histologic grade, lymph node status) and predictive factors (molecular subtypes based on immunohistochemical analyses of hormone receptor status (estrogen and progesterone) and Her2 status) were available for 8344 women in Norway aged 50-69 at diagnosis of breast cancer, 2005-2011. A total of 255 breast cancer deaths were registered by the end of 2011. Kaplan-Meier method was used to estimate six years breast cancer specific survival and Cox proportional hazard model to estimate hazard ratio (HR) for breast cancer death by detection mode, adjusting for prognostic and predictive factors. Women with screen-detected cancer had favourable prognostic and predictive tumour characteristics compared with interval cancers and those detected outside the screening programme. The favourable characteristics were present for screen-detected cancers, also within the subtypes. Adjusted HR of dying from breast cancer was two times higher for women with symptomatic breast cancer (interval or outside the screening), using screen-detected tumours as the reference. Detection mode is an independent prognostic factor for women diagnosed with breast cancer. Information on detection mode might be relevant for patient management to avoid overtreatment. © The Author(s) 2015.
Choi, Jong-Ho; Suh, Yun-Suhk; Choi, Yunhee; Han, Jiyeon; Kim, Tae Han; Park, Shin-Hoo; Kong, Seong-Ho; Lee, Hyuk-Joon; Yang, Han-Kwang
2018-02-01
The role of neutrophil-to-lymphocyte ratio (NLR) and preoperative prediction model in gastric cancer is controversial, while postoperative prognostic models are available. This study investigated NLR as a preoperative prognostic indicator in gastric cancer. We reviewed patients with primary gastric cancer who underwent surgery during 2007-2010. Preoperative clinicopathologic factors were analyzed with their interaction and used to develop a prognosis prediction nomogram. That preoperative prediction nomogram was compared to a nomogram using pTNM or a historical postoperative prediction nomogram. The contribution of NLR to a preoperative nomogram was evaluated with integrated discrimination improvement (IDI). Using 2539 records, multivariable analysis revealed that NLR was one of the independent prognostic factors and had a significant interaction with only age among other preoperative factors (especially significant in patients < 50 years old). NLR was constantly significant between 1.1 and 3.1 without any distinctive cutoff value. Preoperative prediction nomogram using NLR showed a Harrell's C-index of 0.79 and an R 2 of 25.2%, which was comparable to the C-index of 0.78 and 0.82 and R 2 of 26.6 and 25.8% from nomogram using pTNM and a historical postoperative prediction nomogram, respectively. IDI of NLR to nomogram in the overall population was 0.65%, and that of patients < 50 years old was 2.72%. NLR is an independent prognostic factor for gastric cancer, especially in patients < 50 years old. A preoperative prediction nomogram using NLR can predict prognosis of gastric cancer as effectively as pTNM and a historical postoperative prediction nomogram.
Low Expression of Mucin-4 Predicts Poor Prognosis in Patients With Clear-Cell Renal Cell Carcinoma
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
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
Chua, Daniel T T; Sham, Jonathan S T; Hung, Kwan-Ngai; Leung, Lucullus H T; Au, Gordon K H
2006-12-01
Stereotactic radiosurgery has been employed as a salvage treatment of local failures of nasopharyngeal carcinoma (NPC). To identify patients that would benefit from radiosurgery, we reviewed our data with emphasis on factors that predicted treatment outcome. A total of 48 patients with local failures of NPC were treated by stereotactic radiosurgery between March 1996 and February 2005. Radiosurgery was administered using a modified linear accelerator with single or multiple isocenters to deliver a median dose of 12.5 Gy to the target periphery. Median follow-up was 54 months. Five-year local failure-free probability after radiosurgery was 47.2% and 5-year overall survival rate was 46.9%. Neuroendocrine complications occurred in 27% of patients but there were no treatment-related deaths. Time interval from primary radiotherapy, retreatment T stage, prior local failures and tumor volume were significant predictive factors of local control and/or survival whereas age was of marginal significance in predicting survival. A radiosurgery prognostic scoring system was designed based on these predictive factors. Five-year local failure-free probabilities in patients with good, intermediate and poor prognostic scores were 100%, 42.5%, and 9.6%. The corresponding five-year overall survival rates were 100%, 51.1%, and 0%. Important factors that predicted tumor control and survival after radiosurgery were identified. Patients with good prognostic score should be treated by radiosurgery in view of the excellent results. Patients with intermediate prognostic score may also be treated by radiosurgery but those with poor prognostic score should receive other salvage treatments.
de Rooij, Mariëtte; van der Leeden, Marike; Heymans, Martijn W; Holla, Jasmijn F M; Häkkinen, Arja; Lems, Willem F; Roorda, Leo D; Veenhof, Cindy; Sanchez-Ramirez, Diana C; de Vet, Henrica C W; Dekker, Joost
2016-04-01
To systematically summarize the literature on the course of pain in patients with knee osteoarthritis (OA), prognostic factors that predict deterioration of pain, the course of physical functioning, and prognostic factors that predict deterioration of physical functioning in persons with knee OA. A search was conducted in PubMed, CINAHL, Embase, Psych-INFO, and SPORTDiscus up to January 2014. A meta-analysis and a qualitative data synthesis were performed. Of the 58 studies included, 39 were of high quality. High heterogeneity across studies (I(2) >90%) and within study populations (reflected by large SDs of change scores) was found. Therefore, the course of pain and physical functioning was interpreted to be indistinct. We found strong evidence for a number of prognostic factors predicting deterioration in pain (e.g., higher knee pain at baseline, bilateral knee symptoms, and depressive symptoms). We also found strong evidence for a number of prognostic factors predicting deterioration in physical functioning (e.g., worsening in radiographic OA, worsening of knee pain, lower knee extension muscle strength, lower walking speed, and higher comorbidity count). Because of high heterogeneity across studies and within study populations, no conclusions can be drawn with regard to the course of pain and physical functioning. These findings support current research efforts to define subgroups or phenotypes within knee OA populations. Strong evidence was found for knee characteristics, clinical factors, and psychosocial factors as prognostics of deterioration of pain and physical functioning. © 2016, American College of Rheumatology.
Cates, Justin Mm; Dupont, William D
2017-01-01
The current College of American Pathologists cancer template for reporting biopsies of bone tumors recommends including information that is of unproven prognostic significance for osteosarcoma, such as the presence of spontaneous tumor necrosis and mitotic rate. Conversely, the degree of cytologic anaplasia (degree of differentiation) is not reported in this template. This retrospective cohort study of 125 patients with high-grade osteosarcoma was performed to evaluate the prognostic impact of these factors in diagnostic biopsy specimens in predicting the clinical outcome and response to neoadjuvant chemotherapy. Multivariate Cox regression was performed to adjust survival analyses for well-established prognostic factors. Multivariate logistic regression was used to determine odds ratios for good chemotherapy response (≥90% tumor necrosis). Osteosarcomas with severe anaplasia were independently associated with increased overall and disease-free survival, but mitotic rate and spontaneous necrosis had no prognostic impact after controlling for other confounding factors. Mitotic rate showed a trend towards increased odds of a good histologic response, but this effect was diminished after controlling for other predictive factors. Neither spontaneous necrosis nor the degree of cytologic anaplasia observed in biopsy specimens was predictive of a good response to chemotherapy. Mitotic rate and spontaneous tumor necrosis observed in pretreatment biopsy specimens of high-grade osteosarcoma are not strong independent prognostic factors for clinical outcome or predictors of response to neoadjuvant chemotherapy. Therefore, reporting these parameters for osteosarcoma, as recommended in the College of American Pathologists Bone Biopsy template, does not appear to have clinical utility. In contrast, histologic grading schemes for osteosarcoma based on the degree of cytologic anaplasia may have independent prognostic value and should continue to be evaluated.
Profiles of neurological outcome prediction among intensivists.
Racine, Eric; Dion, Marie-Josée; Wijman, Christine A C; Illes, Judy; Lansberg, Maarten G
2009-12-01
Advances in intensive care medicine have increased survival rates of patients with critical neurological conditions. The focus of prognostication for such patients is therefore shifting from predicting chances of survival to meaningful neurological recovery. This study assessed the variability in long-term outcome predictions among physicians and aimed to identify factors that may account for this variability. Based on a clinical vignette describing a comatose patient suffering from post-anoxic brain injury intensivists were asked in a semi-structured interview about the patient's specific neurological prognosis and about prognostication in general. Qualitative research methods were used to identify areas of variability in prognostication and to classify physicians according to specific prognostication profiles. Quantitative statistics were used to assess for associations between prognostication profiles and physicians' demographic and practice characteristics. Eighteen intensivists participated. Functional outcome predictions varied along an evaluative dimension (fair/good-poor) and a confidence dimension (certain-uncertain). More experienced physicians tended to be more pessimistic about the patient's functional outcome and more certain of their prognosis. Attitudes toward quality of life varied along an evaluative dimension (good-poor) and a "style" dimension (objective-subjective). Older and more experienced physicians were more likely to express objective judgments of quality of life and to predict a worse quality of life for the patient than their younger and less experienced counterparts. Various prognostication profiles exist among intensivists. These may be dictated by factors such as physicians' age and clinical experience. Awareness of these associations may be a first step to more uniform prognostication.
Predictive and Prognostic Factors in Ovarian and Uterine Carcinosarcomas
Cicin, İrfan; Özatlı, Tahsin; Türkmen, Esma; Özturk, Türkan; Özçelik, Melike; Çabuk, Devrim; Gökdurnalı, Ayşe; Balvan, Özlem; Yıldız, Yaşar; Şeker, Metin; Özdemir, Nuriye; Yapar, Burcu; Tanrıverdi, Özgür; Günaydin, Yusuf; Menekşe, Serkan; Öksüzoğlu, Berna; Aksoy, Asude; Erdogan, Bülent; Bekir Hacıoglu, M.; Arpaci, Erkan; Sevinç, Alper
2016-01-01
Background: Prognostic factors and the standard treatment approach for gynaecological carcinosarcomas have not yet been clearly defined. Although carcinosarcomas are more aggressive than pure epithelial tumours, they are treated similarly. Serous/clear cell and endometrioid components may be predictive factors for the efficacy of adjuvant chemotherapy (CT) or radiotherapy (RT) or RT in patients with uterine and ovarian carcinosarcomas. Heterologous carcinosarcomas may benefit more from adjuvant CT. Aims: We aimed to define the prognostic and predictive factors associated with treatment options in ovarian (OCS) and uterine carcinosarcoma (UCS). Study Design: Retrospective cross-sectional study Methods: We retrospectively reviewed the medical records of patients with ovarian and uterine carcinosarcoma from 2000 to 2013, and 127 women were included in this study (24 ovarian and 103 uterine). Patients admitted to seventeen oncology centres in Turkey between 2000 and December 2013 with a histologically proven diagnosis of uterine carcinosarcoma with FIGO 2009 stage I–III and patients with sufficient data obtained from well-kept medical records were included in this study. Stage IV tumours were excluded. The patient records were retrospectively reviewed. Data from 104 patients were evaluated for this study. Results: Age (≥70 years) was a poor prognostic factor for UCS (p=0.036). Pelvic±para aortic lymph node dissection did not affect overall survival (OS) (p=0.35). Macroscopic residual disease was related with OS (p<0.01). The median OS was significantly longer in stage I–II patients than stage III patients (p=0.03). Adjuvant treatment improved OS (p=0.013). Adjuvant radiotherapy tended to increase the median OS (p=0.075). However, this tendency was observed in UCS (p=0.08) rather than OCS (p=0.6).Adjuvant chemotherapy had no effect on OS (p=0.15).Adjuvant radiotherapy significantly prolonged the median OS in patients with endometrioid component (p=0.034). A serous/clear cell component was a negative prognostic factor (p=0.035). Patients with serous/clear cell histology for whom adjuvant chemotherapy was applied had significantly longer OS (p=0.019), and there was no beneficial effect of adjuvant radiotherapy (p=0.4). Adjuvant chemotherapy was effective in heterologous tumours (p=0.026). In multivariate analysis, the stage and chemotherapy were prognostic factors for all patients. Age was an independent prognostic factor for UCS. However, serous/clear cell histology and radiotherapy tended to be significant prognostic factors. Conclusion: The primary location, the histological type of sarcomatous and the epithelial component may be predictive factors for the efficacy of chemotherapy or radiotherapy in UCS and OCS. PMID:27761279
Prognostic factors in prostate cancer.
Braeckman, Johan; Michielsen, Dirk
2007-01-01
In the nineteenth century the main goal of medicine was predictive: diagnose the disease and achieve a satisfying prognosis of the patient's chances. Today the effort has shifted to cure the disease. Since the twentieth century, the word prognosis has also been used in nonmedical contexts, for example in corporate finance or elections. The most accurate form of prognosis is achieved statistically. Based on different prognostic factors it should be possible to tell patients how they are expected to do after prostate cancer has been diagnosed and how different treatments may change this outcome. A prognosis is a prediction. The word prognosis comes from the Greek word (see text) and means foreknowing. In the nineteenth century this was the main goal of medicine: diagnose the disease and achieve a satisfying prognosis of the patient's chances. Today the effort has shifted towards seeking a cure. Prognostic factors in (prostate) cancer are defined as "variables that can account for some of the heterogeneity associated with the expected course and outcome of a disease". Bailey defined prognosis as "a reasoned forecast concerning the course, pattern, progression, duration, and end of the disease. Prognostic factors are not only essential to understand the natural history and the course of the disease, but also to predict possible different outcomes of different treatments or perhaps no treatment at all. This is extremely important in a disease like prostate cancer where there is clear evidence that a substantial number of cases discovered by prostate-specific antigen (PSA) testing are unlikely ever to become clinically significant, not to mention mortal. Furthermore, prognostic factors are of paramount importance for correct interpretation of clinical trials and for the construction of future trials. Finally, according to WHO national screening committee criteria for implementing a national screening programme, widely accepted prognostic factors must be defined before assessing screening.
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.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kim, Jun-Sang, E-mail: k423j@cnu.ac.kr; Cancer Research Institute, Chungnam National University, Daejeon; Kim, Jin-Man
Purpose: Human apurinic endonuclease/redox factor 1 (APE/Ref-1) mediates repair of radiation-induced DNA lesions and regulates transcription via redox-based activation. We investigated the predictive and prognostic significance of APE/Ref-1 expression in pretreatment biopsy specimens in locally advanced rectal cancer (LARC) (cT3-T4 or N+). Methods and Materials: APE/Ref-1 expression was analyzed by immunohistochemistry in pretreatment biopsy specimens obtained from 83 patients with LARC. Patients received preoperative radiotherapy of 50.4 Gy in 28 fractions, combined with oral capecitabine and leucovorin chemotherapy, followed by curative surgery. The prognostic significance of various clinicopathologic characteristics, including APE/Ref-1 protein expression, was evaluated. Results: APE/Ref-1 was expressed inmore » 97% of patient samples. Exclusive APE/Ref-1 nuclear staining was observed in 49 of 83 samples (59%), and mixed nuclear and cytoplasmic staining was observed in 31 samples (37%). APE/Ref-1 nuclear expression levels were low in 49 patients (59%) and high in 34 patients (41%). The level of APE/Ref-1 nuclear expression was not a prognostic factor for overall and disease-free survival. Cytoplasmic expression of APE/Ref-1 was a borderline-significant predictive factor for pathologic tumor response (p = 0.08) and a significant prognostic factor for disease-free survival, as shown by univariate analysis (p = 0.037). Multivariate analysis confirmed that cytoplasmic localization of APE/Ref-1 is a significant predictor of disease-free survival (hazard ratio, 0.45; p = 0.046). Conclusions: APE/Ref-1 was expressed in a majority of pretreatment biopsy specimens from patients with LARC. The level of APE/Ref-1 nuclear expression was not a significant predictive and prognostic factor; however, cytoplasmic localization of the protein was negatively associated with disease-free survival. These results indicate that cytoplasmic expression of APE/Ref-1 represents an adverse prognostic factor for LARC patients who receive preoperative radiochemotherapy.« less
Distinguishing prognostic and predictive biomarkers: An information theoretic approach.
Sechidis, Konstantinos; Papangelou, Konstantinos; Metcalfe, Paul D; Svensson, David; Weatherall, James; Brown, Gavin
2018-05-02
The identification of biomarkers to support decision-making is central to personalised medicine, in both clinical and research scenarios. The challenge can be seen in two halves: identifying predictive markers, which guide the development/use of tailored therapies; and identifying prognostic markers, which guide other aspects of care and clinical trial planning, i.e. prognostic markers can be considered as covariates for stratification. Mistakenly assuming a biomarker to be predictive, when it is in fact largely prognostic (and vice-versa) is highly undesirable, and can result in financial, ethical and personal consequences. We present a framework for data-driven ranking of biomarkers on their prognostic/predictive strength, using a novel information theoretic method. This approach provides a natural algebra to discuss and quantify the individual predictive and prognostic strength, in a self-consistent mathematical framework. Our contribution is a novel procedure, INFO+, which naturally distinguishes the prognostic vs predictive role of each biomarker and handles higher order interactions. In a comprehensive empirical evaluation INFO+ outperforms more complex methods, most notably when noise factors dominate, and biomarkers are likely to be falsely identified as predictive, when in fact they are just strongly prognostic. Furthermore, we show that our methods can be 1-3 orders of magnitude faster than competitors, making it useful for biomarker discovery in 'big data' scenarios. Finally, we apply our methods to identify predictive biomarkers on two real clinical trials, and introduce a new graphical representation that provides greater insight into the prognostic and predictive strength of each biomarker. R implementations of the suggested methods are available at https://github.com/sechidis. konstantinos.sechidis@manchester.ac.uk. Supplementary data are available at Bioinformatics online.
Zhang, Heng; Wang, Xuefei; Shen, Zhenbin; Xu, Jiejie; Qin, Jing; Sun, Yihong
2015-10-01
Tumor-associated macrophages (TAMs), the most predominant tumor-infiltrating immune cells, are emerging prognostic factors and therapeutic targets for personalized therapy against malignant neoplasms. We aimed to evaluate the prognostic significance of diametrically polarized TAMs in gastric cancer and generate a predictive nomogram to refine a risk stratification system. We evaluated polarized functional status of infiltrated TAMs by immunohistochemical staining of CD68, CD11c, and CD206 in 180 consecutive gastric cancer patients from Zhongshan Hospital, Shanghai, China. Prognostic values were assessed in these patients. We created a predictive nomogram by integrating polarized TAMs with the TNM staging system for overall survival of gastric cancer patients. CD68(+) TAMs display polarized programs comprising CD11c(+) proinflammatory macrophages (M1) and CD206(+) immunosuppressive macrophages (M2) that configure versatile infiltration files in gastric cancer. CD11c(+) TAMs negatively correlated with lymph node metastasis (p = 0.012), whereas CD206(+) TAMs correlated with the Lauren classification (p = 0.031). No prognostic difference was observed for overall survival for CD68 density (high vs low, p = 0.1031), whereas high versus low CD11c density (p < 0.0001) and low vs high CD206 density (p = 0.0105) indicate better overall survival. Multivariate Cox regression analysis identified CD11c and CD206 as independent prognostic factors (p < 0.001 and p = 0.030, respectively), which could be integrated with the TNM staging system to generate a predictive nomogram for patient outcomes. Infiltration of polarized TAMs, a novel identified independent prognostic factor, could be combined with the TNM stage to refine a risk stratification system and better stratify patients with different prognosis. Tipping TAMs to an antitumoral phenotype might be a promising therapeutic target for postoperative treatment.
Hyperfibrinogenemia is a poor prognostic factor in diffuse large B cell lymphoma.
Niu, Jun-Ying; Tian, Tian; Zhu, Hua-Yuan; Liang, Jin-Hua; Wu, Wei; Cao, Lei; Lu, Rui-Nan; Wang, Li; Li, Jian-Yong; Xu, Wei
2018-06-02
Diffuse large B cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphomas worldwide. Previous studies indicated that hyperfibrinogenemia was a poor predictor in various tumors. The purpose of our study was to evaluate the prognostic effect of hyperfibrinogenemia in DLBCL. Data of 228 patients, who were diagnosed with DLBCL in our hospital between May 2009 and February 2016, were analyzed retrospectively. The Kaplan-Meier method and Cox regression were performed to find prognostic factors associated with progression-free survival (PFS) and overall survival (OS). Receiver operator characteristic (ROC) curve and the areas under the curve were used to evaluate the predictive accuracy of predictors. Comparison of characters between groups indicated that patients with high National Comprehensive Cancer Network-International Prognostic Index (NCCN-IPI) score (4-8) and advanced stage (III-IV) were more likely to suffer from hyperfibrinogenemia. The Kaplan-Meier method revealed that patients with hyperfibrinogenemia showed inferior PFS (P < 0.001) and OS (P < 0.001) than those without hyperfibrinogenemia. Multivariate analysis showed that hyperfibrinogenemia was an independent prognostic factor associated with poor outcomes (HR = 1.90, 95% CI: 1.15-3.16 for PFS, P = 0.013; HR = 2.65, 95% CI: 1.46-4.79 for OS, P = 0.001). We combined hyperfibrinogenemia and NCCN-IPI to build a new prognostic index (NPI). The NPI was demonstrated to have a superior predictive effect on prognosis (P = 0.0194 for PFS, P = 0.0034 for OS). Hyperfibrinogenemia was demonstrated to be able to predict poor outcome in DLBCL, especially for patients with advanced stage and high NCCN-IPI score. Adding hyperfibrinogenemia to NCCN-IPI could significantly improve the predictive effect of NCCN-IPI.
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.
Koorevaar, Rinco C T; Van't Riet, Esther; Ipskamp, Marcel; Bulstra, Sjoerd K
2017-03-01
Frozen shoulder is a potential complication after shoulder surgery. It is a clinical condition that is often associated with marked disability and can have a profound effect on the patient's quality of life. The incidence, etiology, pathology and prognostic factors of postoperative frozen shoulder after shoulder surgery are not known. The purpose of this explorative study was to determine the incidence of postoperative frozen shoulder after various operative shoulder procedures. A second aim was to identify prognostic factors for postoperative frozen shoulder after shoulder surgery. 505 consecutive patients undergoing elective shoulder surgery were included in this prospective cohort study. Follow-up was 6 months after surgery. A prediction model was developed to identify prognostic factors for postoperative frozen shoulder after shoulder surgery using the TRIPOD guidelines. We nominated five potential predictors: gender, diabetes mellitus, type of physiotherapy, arthroscopic surgery and DASH score. Frozen shoulder was identified in 11% of the patients after shoulder surgery and was more common in females (15%) than in males (8%). Frozen shoulder was encountered after all types of operative procedures. A prediction model based on four variables (diabetes mellitus, specialized shoulder physiotherapy, arthroscopic surgery and DASH score) discriminated reasonably well with an AUC of 0.712. Postoperative frozen shoulder is a serious complication after shoulder surgery, with an incidence of 11%. Four prognostic factors were identified for postoperative frozen shoulder: diabetes mellitus, arthroscopic surgery, specialized shoulder physiotherapy and DASH score. The combination of these four variables provided a prediction rule for postoperative frozen shoulder with reasonable fit. Level II, prospective cohort study.
Kim, Jae Hyun; Lee, Jun Yeop; Kim, Hae Koo; Lee, Jin Wook; Jung, Sung Gyu; Jung, Kyoungwon; Kim, Sung Eun; Moon, Won; Park, Moo In; Park, Seun Ja
2017-01-01
AIM To evaluate the prognostic value of the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in patients with colorectal cancer (CRC). METHODS Between April 1996 and December 2010, medical records from a total of 1868 patients with CRC were retrospectively reviewed. The values of simple inflammatory markers including NLR and PLR in predicting the long-term outcomes of these patients were evaluated using Kaplan-Meier curves and Cox regression models. RESULTS The median follow-up duration was 46 mo (interquartile range, 22-73). The estimation of NLR and PLR was based on the time of diagnosis. In multivariate Cox regression analysis, high NLR (≥ 3.0) and high PLR (≥ 160) were independent risk factors predicting poor long-term outcomes in patients with stage III and IV CRC. However, high NLR and high PLR were not prognostic factors in patients with stage I and II CRC. CONCLUSION In this study, we identified that high NLR (≥ 3.0) and high PLR (≥ 160) are useful prognostic factors to predict long-term outcomes in patients with stage III and IV CRC. PMID:28210087
NASA Astrophysics Data System (ADS)
Javed, Kamran; Gouriveau, Rafael; Zerhouni, Noureddine
2017-09-01
Integrating prognostics to a real application requires a certain maturity level and for this reason there is a lack of success stories about development of a complete Prognostics and Health Management system. In fact, the maturity of prognostics is closely linked to data and domain specific entities like modeling. Basically, prognostics task aims at predicting the degradation of engineering assets. However, practically it is not possible to precisely predict the impending failure, which requires a thorough understanding to encounter different sources of uncertainty that affect prognostics. Therefore, different aspects crucial to the prognostics framework, i.e., from monitoring data to remaining useful life of equipment need to be addressed. To this aim, the paper contributes to state of the art and taxonomy of prognostics approaches and their application perspectives. In addition, factors for prognostics approach selection are identified, and new case studies from component-system level are discussed. Moreover, open challenges toward maturity of the prognostics under uncertainty are highlighted and scheme for an efficient prognostics approach is presented. Finally, the existing challenges for verification and validation of prognostics at different technology readiness levels are discussed with respect to open challenges.
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.
Prognosis in advanced lung cancer--A prospective study examining key clinicopathological factors.
Simmons, Claribel P; Koinis, Filippos; Fallon, Marie T; Fearon, Kenneth C; Bowden, Jo; Solheim, Tora S; Gronberg, Bjorn Henning; McMillan, Donald C; Gioulbasanis, Ioannis; Laird, Barry J
2015-06-01
In patients with advanced incurable lung cancer deciding as to the most appropriate treatment (e.g., chemotherapy or supportive care only) is challenging. In such patients the TNM classification system has reached its ceiling therefore other factors are used to assess prognosis and as such, guide treatment. Performance status (PS), weight loss and inflammatory biomarkers (Glasgow Prognostic Score (mGPS)) predict survival in advanced lung cancer however these have not been compared. This study compares key prognostic factors in advanced lung cancer. Patients with newly diagnosed advanced lung cancer were recruited and demographics, weight loss, other prognostic factors (mGPS, PS) were collected. Kaplan-Meier and Cox regression methods were used to compare these prognostic factors. 390 patients with advanced incurable lung cancer were recruited; 341 were male, median age was 66 years (IQR 59-73) and patients had stage IV non-small cell (n=288) (73.8%) or extensive stage small cell lung cancer (n=102) (26.2%). The median survival was 7.8 months. On multivariate analysis only performance status (HR 1.74 CI 1.50-2.02) and mGPS (HR 1.67, CI 1.40-2.00) predicted survival (p<0.001). Survival at 3 months ranged from 99% (ECOG 0-1) to 74% (ECOG 2) and using mGPS, from 99% (mGPS0) to 71% (mGPS2). In combination, survival ranged from 99% (mGPS 0, ECOG 0-1) to 33% (mGPS2, ECOG 3). Performance status and the mGPS are superior prognostic factors in advanced lung cancer. In combination, these improved survival prediction compared with either alone. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.
Onukwugha, Eberechukwu; Qi, Ran; Jayasekera, Jinani; Zhou, Shujia
2016-02-01
Prognostic classification approaches are commonly used in clinical practice to predict health outcomes. However, there has been limited focus on use of the general approach for predicting costs. We applied a grouping algorithm designed for large-scale data sets and multiple prognostic factors to investigate whether it improves cost prediction among older Medicare beneficiaries diagnosed with prostate cancer. We analysed the linked Surveillance, Epidemiology and End Results (SEER)-Medicare data, which included data from 2000 through 2009 for men diagnosed with incident prostate cancer between 2000 and 2007. We split the survival data into two data sets (D0 and D1) of equal size. We trained the classifier of the Grouping Algorithm for Cancer Data (GACD) on D0 and tested it on D1. The prognostic factors included cancer stage, age, race and performance status proxies. We calculated the average difference between observed D1 costs and predicted D1 costs at 5 years post-diagnosis with and without the GACD. The sample included 110,843 men with prostate cancer. The median age of the sample was 74 years, and 10% were African American. The average difference (mean absolute error [MAE]) per person between the real and predicted total 5-year cost was US$41,525 (MAE US$41,790; 95% confidence interval [CI] US$41,421-42,158) with the GACD and US$43,113 (MAE US$43,639; 95% CI US$43,062-44,217) without the GACD. The 5-year cost prediction without grouping resulted in a sample overestimate of US$79,544,508. The grouping algorithm developed for complex, large-scale data improves the prediction of 5-year costs. The prediction accuracy could be improved by utilization of a richer set of prognostic factors and refinement of categorical specifications.
Perry, Anamarija M; Cardesa-Salzmann, Teresa M; Meyer, Paul N; Colomo, Luis; Smith, Lynette M; Fu, Kai; Greiner, Timothy C; Delabie, Jan; Gascoyne, Randy D; Rimsza, Lisa; Jaffe, Elaine S; Ott, German; Rosenwald, Andreas; Braziel, Rita M; Tubbs, Raymond; Cook, James R; Staudt, Louis M; Connors, Joseph M; Sehn, Laurie H; Vose, Julie M; López-Guillermo, Armando; Campo, Elias; Chan, Wing C; Weisenburger, Dennis D
2012-09-13
Biologic factors that predict the survival of patients with a diffuse large B-cell lymphoma, such as cell of origin and stromal signatures, have been discovered by gene expression profiling. We attempted to simulate these gene expression profiling findings and create a new biologic prognostic model based on immunohistochemistry. We studied 199 patients (125 in the training set, 74 in the validation set) with de novo diffuse large B-cell lymphoma treated with rituximab and CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) or CHOP-like therapies, and immunohistochemical stains were performed on paraffin-embedded tissue microarrays. In the model, 1 point was awarded for each adverse prognostic factor: nongerminal center B cell-like subtype, SPARC (secreted protein, acidic, and rich in cysteine) < 5%, and microvascular density quartile 4. The model using these 3 biologic markers was highly predictive of overall survival and event-free survival in multivariate analysis after adjusting for the International Prognostic Index in both the training and validation sets. This new model delineates 2 groups of patients, 1 with a low biologic score (0-1) and good survival and the other with a high score (2-3) and poor survival. This new biologic prognostic model could be used with the International Prognostic Index to stratify patients for novel or risk-adapted therapies.
Prognostic Indexes for Brain Metastases: Which Is the Most Powerful?
DOE Office of Scientific and Technical Information (OSTI.GOV)
Arruda Viani, Gustavo, E-mail: gusviani@gmail.com; Bernardes da Silva, Lucas Godoi; Stefano, Eduardo Jose
Purpose: The purpose of the present study was to compare the prognostic indexes (PIs) of patients with brain metastases (BMs) treated with whole brain radiotherapy (WBRT) using an artificial neural network. This analysis is important, because it evaluates the prognostic power of each PI to guide clinical decision-making and outcomes research. Methods and Materials: A retrospective prognostic study was conducted of 412 patients with BMs who underwent WBRT between April 1998 and March 2010. The eligibility criteria for patients included having undergone WBRT or WBRT plus neurosurgery. The data were analyzed using the artificial neural network. The input neural datamore » consisted of all prognostic factors included in the 5 PIs (recursive partitioning analysis, graded prognostic assessment [GPA], basic score for BMs, Rotterdam score, and Germany score). The data set was randomly divided into 300 training and 112 testing examples for survival prediction. All 5 PIs were compared using our database of 412 patients with BMs. The sensibility of the 5 indexes to predict survival according to their input variables was determined statistically using receiver operating characteristic curves. The importance of each variable from each PI was subsequently evaluated. Results: The overall 1-, 2-, and 3-year survival rate was 22%, 10.2%, and 5.1%, respectively. All classes of PIs were significantly associated with survival (recursive partitioning analysis, P < .0001; GPA, P < .0001; basic score for BMs, P = .002; Rotterdam score, P = .001; and Germany score, P < .0001). Comparing the areas under the curves, the GPA was statistically most sensitive in predicting survival (GPA, 86%; recursive partitioning analysis, 81%; basic score for BMs, 79%; Rotterdam, 73%; and Germany score, 77%; P < .001). Among the variables included in each PI, the performance status and presence of extracranial metastases were the most important factors. Conclusion: A variety of prognostic models describe the survival of patients with BMs to a more or less satisfactory degree. Among the 5 PIs evaluated in the present study, GPA was the most powerful in predicting survival. Additional studies should include emerging biologic prognostic factors to improve the sensibility of these PIs.« less
Roelen, Corné A M; Stapelfeldt, Christina M; Heymans, Martijn W; van Rhenen, Willem; Labriola, Merete; Nielsen, Claus V; Bültmann, Ute; Jensen, Chris
2015-06-01
To validate Dutch prognostic models including age, self-rated health and prior sickness absence (SA) for ability to predict high SA in Danish eldercare. The added value of work environment variables to the models' risk discrimination was also investigated. 2,562 municipal eldercare workers (95% women) participated in the Working in Eldercare Survey. Predictor variables were measured by questionnaire at baseline in 2005. Prognostic models were validated for predictions of high (≥30) SA days and high (≥3) SA episodes retrieved from employer records during 1-year follow-up. The accuracy of predictions was assessed by calibration graphs and the ability of the models to discriminate between high- and low-risk workers was investigated by ROC-analysis. The added value of work environment variables was measured with Integrated Discrimination Improvement (IDI). 1,930 workers had complete data for analysis. The models underestimated the risk of high SA in eldercare workers and the SA episodes model had to be re-calibrated to the Danish data. Discrimination was practically useful for the re-calibrated SA episodes model, but not the SA days model. Physical workload improved the SA days model (IDI = 0.40; 95% CI 0.19-0.60) and psychosocial work factors, particularly the quality of leadership (IDI = 0.70; 95% CI 053-0.86) improved the SA episodes model. The prognostic model predicting high SA days showed poor performance even after physical workload was added. The prognostic model predicting high SA episodes could be used to identify high-risk workers, especially when psychosocial work factors are added as predictor variables.
Novel immunological and nutritional-based prognostic index for gastric cancer.
Sun, Kai-Yu; Xu, Jian-Bo; Chen, Shu-Ling; Yuan, Yu-Jie; Wu, Hui; Peng, Jian-Jun; Chen, Chuang-Qi; Guo, Pi; Hao, Yuan-Tao; He, Yu-Long
2015-05-21
To assess the prognostic significance of immunological and nutritional-based indices, including the prognostic nutritional index (PNI), neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio in gastric cancer. We retrospectively reviewed 632 gastric cancer patients who underwent gastrectomy between 1998 and 2008. Areas under the receiver operating characteristic curve were calculated to compare the predictive ability of the indices, together with estimating the sensitivity, specificity and agreement rate. Univariate and multivariate analyses were performed to identify risk factors for overall survival (OS). Propensity score analysis was performed to adjust variables to control for selection bias. Each index could predict OS in gastric cancer patients in univariate analysis, but only PNI had independent prognostic significance in multivariate analysis before and after adjustment with propensity scoring (hazard ratio, 1.668; 95% confidence interval: 1.368-2.035). In subgroup analysis, a low PNI predicted a significantly shorter OS in patients with stage II-III disease (P = 0.019, P < 0.001), T3-T4 tumors (P < 0.001), or lymph node metastasis (P < 0.001). Canton score, a combination of PNI, NLR, and platelet, was a better indicator for OS than PNI, with the largest area under the curve for 12-, 36-, 60-mo OS and overall OS (P = 0.022, P = 0.030, P < 0.001, and P = 0.024, respectively). The maximum sensitivity, specificity, and agreement rate of Canton score for predicting prognosis were 84.6%, 34.9%, and 70.1%, respectively. PNI is an independent prognostic factor for OS in gastric cancer. Canton score can be a novel preoperative prognostic index in gastric cancer.
Nordeman, Lena; Gunnarsson, Ronny; Mannerkorpi, Kaisa
2014-05-01
To investigate prognostic factors for future work ability in women with chronic low back pain (CLBP) consulting primary health care. A 2-year prospective longitudinal cohort study of female patients with CLBP within the primary health care was conducted. Patients were assessed at the first assessment and after 2 years. Prognostic factors for work ability (yes/no) were analyzed by multivariate regression. A total of 130 patients were included at first assessment. After 2 years, 123 patients (95%) were followed up. The 6-minute walk test, depression, and earlier work ability predicted work ability at the 2-year follow-up. A nomogram was constructed to assess the probability of future work ability. The 6-minute walk test, work ability, and depression predicted work ability for women with CLBP after 2 years.
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.
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.
Prognostic value of preoperative serum CA 242 in Esophageal squamous cell carcinoma cases.
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.
Ting, Hui-Min; Chang, Liyun; Huang, Yu-Jie; Wu, Jia-Ming; Wang, Hung-Yu; Horng, Mong-Fong; Chang, Chun-Ming; Lan, Jen-Hong; Huang, Ya-Yu; Fang, Fu-Min; Leung, Stephen Wan
2014-01-01
Purpose The aim of this study was to develop a multivariate logistic regression model with least absolute shrinkage and selection operator (LASSO) to make valid predictions about the incidence of moderate-to-severe patient-rated xerostomia among head and neck cancer (HNC) patients treated with IMRT. Methods and Materials Quality of life questionnaire datasets from 206 patients with HNC were analyzed. The European Organization for Research and Treatment of Cancer QLQ-H&N35 and QLQ-C30 questionnaires were used as the endpoint evaluation. The primary endpoint (grade 3+ xerostomia) was defined as moderate-to-severe xerostomia at 3 (XER3m) and 12 months (XER12m) after the completion of IMRT. Normal tissue complication probability (NTCP) models were developed. The optimal and suboptimal numbers of prognostic factors for a multivariate logistic regression model were determined using the LASSO with bootstrapping technique. Statistical analysis was performed using the scaled Brier score, Nagelkerke R2, chi-squared test, Omnibus, Hosmer-Lemeshow test, and the AUC. Results Eight prognostic factors were selected by LASSO for the 3-month time point: Dmean-c, Dmean-i, age, financial status, T stage, AJCC stage, smoking, and education. Nine prognostic factors were selected for the 12-month time point: Dmean-i, education, Dmean-c, smoking, T stage, baseline xerostomia, alcohol abuse, family history, and node classification. In the selection of the suboptimal number of prognostic factors by LASSO, three suboptimal prognostic factors were fine-tuned by Hosmer-Lemeshow test and AUC, i.e., Dmean-c, Dmean-i, and age for the 3-month time point. Five suboptimal prognostic factors were also selected for the 12-month time point, i.e., Dmean-i, education, Dmean-c, smoking, and T stage. The overall performance for both time points of the NTCP model in terms of scaled Brier score, Omnibus, and Nagelkerke R2 was satisfactory and corresponded well with the expected values. Conclusions Multivariate NTCP models with LASSO can be used to predict patient-rated xerostomia after IMRT. PMID:24586971
Lee, Tsair-Fwu; Chao, Pei-Ju; Ting, Hui-Min; Chang, Liyun; Huang, Yu-Jie; Wu, Jia-Ming; Wang, Hung-Yu; Horng, Mong-Fong; Chang, Chun-Ming; Lan, Jen-Hong; Huang, Ya-Yu; Fang, Fu-Min; Leung, Stephen Wan
2014-01-01
The aim of this study was to develop a multivariate logistic regression model with least absolute shrinkage and selection operator (LASSO) to make valid predictions about the incidence of moderate-to-severe patient-rated xerostomia among head and neck cancer (HNC) patients treated with IMRT. Quality of life questionnaire datasets from 206 patients with HNC were analyzed. The European Organization for Research and Treatment of Cancer QLQ-H&N35 and QLQ-C30 questionnaires were used as the endpoint evaluation. The primary endpoint (grade 3(+) xerostomia) was defined as moderate-to-severe xerostomia at 3 (XER3m) and 12 months (XER12m) after the completion of IMRT. Normal tissue complication probability (NTCP) models were developed. The optimal and suboptimal numbers of prognostic factors for a multivariate logistic regression model were determined using the LASSO with bootstrapping technique. Statistical analysis was performed using the scaled Brier score, Nagelkerke R(2), chi-squared test, Omnibus, Hosmer-Lemeshow test, and the AUC. Eight prognostic factors were selected by LASSO for the 3-month time point: Dmean-c, Dmean-i, age, financial status, T stage, AJCC stage, smoking, and education. Nine prognostic factors were selected for the 12-month time point: Dmean-i, education, Dmean-c, smoking, T stage, baseline xerostomia, alcohol abuse, family history, and node classification. In the selection of the suboptimal number of prognostic factors by LASSO, three suboptimal prognostic factors were fine-tuned by Hosmer-Lemeshow test and AUC, i.e., Dmean-c, Dmean-i, and age for the 3-month time point. Five suboptimal prognostic factors were also selected for the 12-month time point, i.e., Dmean-i, education, Dmean-c, smoking, and T stage. The overall performance for both time points of the NTCP model in terms of scaled Brier score, Omnibus, and Nagelkerke R(2) was satisfactory and corresponded well with the expected values. Multivariate NTCP models with LASSO can be used to predict patient-rated xerostomia after IMRT.
Sanjay, Pandanaboyana; de Figueiredo, Rodrigo S; Leaver, Heather; Ogston, Simon; Kulli, Christoph; Polignano, Francesco M; Tait, Iain S
2012-03-10
There is paucity of data on the prognostic value of pre-operative inflammatory response and post-operative lymph node ratio on patient survival after pancreatic-head resection for pancreatic ductal adenocarcinoma. To evaluate the role of the preoperative inflammatory response and postoperative pathology criteria to identify predictive and/or prognostic variables for pancreatic ductal adenocarcinoma. All patients who underwent pancreaticoduodenectomy for pancreatic ductal adenocarcinoma between 2002 and 2008 were reviewed retrospectively. The following impacts on patient survival were assessed: i) preoperative serum CRP levels, white cell count, neutrophil count, neutrophil/lymphocyte ratio, lymphocyte count, platelet/lymphocyte ratio; and ii) post-operative pathology criteria including lymph node status and lymph node ratio. Fifty-one patients underwent potentially curative resection for pancreatic ductal adenocarcinoma during the study period. An elevated preoperative CRP level (greater than 3 mg/L) was found to be a significant adverse prognostic factor (P=0.015) predicting a poor survival, whereas white cell count (P=0.278), neutrophil count (P=0.850), neutrophil/lymphocyte ratio (P=0.272), platelet/lymphocyte ratio (P=0.532) and lymphocyte count (P=0.721) were not significant prognosticators at univariate analysis. Presence of metastatic lymph nodes did not adversely affect survival (P=0.050), however a raised lymph node ratio predicted poor survival at univariate analysis (P<0.001). The preoperative serum CRP level retained significance at multivariate analysis (P=0.011), together with lymph node ratio (P<0.001) and tumour size (greater than 2 cm; P=0.008). A pre-operative elevated serum CRP level and raised post-operative lymph node ratio represent significant independent prognostic factors that predict poor prognosis in patients undergoing curative resection for pancreatic ductal adenocarcinoma. There is potential for future neo-adjuvant and adjuvant treatment strategies in pancreatic cancer to be tailored based on preoperative and postoperative factors that predict a poor survival.
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.
Bruix, Jordi; Cheng, Ann-Lii; Meinhardt, Gerold; Nakajima, Keiko; De Sanctis, Yoriko; Llovet, Josep
2017-11-01
Sorafenib, an oral multikinase inhibitor, significantly prolonged overall survival (OS) vs. placebo in patients with unresectable hepatocellular carcinoma (HCC) in two phase III studies, SHARP (Sorafenib HCC Assessment Randomized Protocol) and Asia Pacific (AP). To assess prognostic factors for HCC and predictive factors of sorafenib benefit, we conducted a pooled exploratory analysis from these placebo-controlled phase III studies. To identify potential prognostic factors for OS, univariate and multivariate (MV) analyses were performed for baseline variables by Cox proportional hazards model. Hazard ratios (HRs) and median OS were evaluated across pooled subgroups. To assess factors predictive of sorafenib benefit, the interaction term between treatment for each subgroup was evaluated by Cox proportional hazard model. In 827 patients (448 sorafenib; 379 placebo) analyzed, strong prognostic factors for poorer OS identified from MV analysis in both treatment arms were presence of macroscopic vascular invasion (MVI), high alpha-fetoprotein (AFP), and high neutrophil-to-lymphocyte ratio (NLR; ⩽ vs. >median [3.1]). Sorafenib OS benefit was consistently observed across all subgroups. Significantly greater OS sorafenib benefit vs. placebo was observed in patients without extrahepatic spread (EHS; HR, 0.55 vs. 0.84), with hepatitis C virus (HCV) (HR, 0.47 vs. 0.81), and a low NLR (HR, 0.59 vs. 0.84). In this exploratory analysis, presence of MVI, high AFP, and high NLR were prognostic factors of poorer OS. Sorafenib benefit was consistently observed irrespective of prognostic factors. Lack of EHS, HCV, and lower NLR were predictive of a greater OS benefit with sorafenib. This exploratory pooled analysis showed that treatment with sorafenib provides a survival benefit in all subgroups of patients with HCC; however, the magnitude of benefit is greater in patients with disease confined to the liver (without extrahepatic spread), or in those with hepatitis C virus, or a lower neutrophil-to-lymphocyte ratio, an indicator of inflammation status. These results help inform the prognosis of patients receiving sorafenib therapy and provide further refinements for the design of trials testing new agents vs. sorafenib. Clinical Trial Numbers: NCT00105443 and NCT00492752. Copyright © 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
Wolfensberger, M
1992-01-01
One of the major short comings of the traditional TNM system is its limited potential for prognostication. With the development of multifactorial analysis techniques, such as Cox's proportional hazards model, it has become possible to simultaneously evaluate a large number of prognostic variables. Cox's model allows both the identification of prognostically relevant variables and the quantification of their prognostic influence. These characteristics make it a helpful tool for analysis as well as for prognostication. The goal of the present study was to develop a prognostic index for patients with carcinoma of the upper aero-digestive tract which makes use of all prognostically relevant variables. To accomplish this, the survival data of 800 patients with squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx or larynx were analyzed. Sixty-one variables were screened for prognostic significance; of these only 19 variables (including age, tumor location, T, N and M stages, resection margins, capsular invasion of nodal metastases, and treatment modality) were found to significantly correlate with prognosis. With the help of Cox's equation, a prognostic index (PI) was computed for every combination of prognostic factors. To test the proposed model, the prognostic index was applied to 120 patients with carcinoma of the oral cavity or oropharynx. A comparison of predicted and observed survival showed good overall correlation, although actual survival tended to be better than predicted.
Honda, Yayoi; Aruga, Tomoyuki; Yamashita, Toshinari; Miyamoto, Hiromi; Horiguchi, Kazumi; Kitagawa, Dai; Idera, Nami; Goto, Risa; Kuroi, Katsumasa
2015-08-01
The prognosis of breast cancer-derived brain metastasis is poor, but new drugs and recent therapeutic strategies have helped extend survival in patients. Prediction of therapeutic responses and outcomes is not yet possible, however. In a retrospective study, we examined prognostic factors in patients with breast cancer-derived brain metastasis, and we tested the prognostic utility of a breast cancer-specific Graded Prognostic Assessment in these patients. Sixty-three patients diagnosed with brain metastasis from breast cancer treated surgically and adjuvantly were included. We examined clinical variables per primary tumor subtype: ER+/HER2- (luminal), HER2+ (human epidermal growth factor receptor type 2-enriched) or ER-/PR-/HER2- (triple negative). We also categorized patients' breast cancer-specific Graded Prognostic Assessment scores and analyzed post-brain metastasis survival time in relation to these categories. The breast cancers comprised the following subtypes: luminal, n = 18; human epidermal growth factor receptor type 2-enriched, n = 27 and triple-negative, n = 18; median survival per subtype was 11, 37 and 3 months, respectively. Survival of human epidermal growth factor receptor type 2-enriched patients was longer, though not significantly (P = 0.188), than that of luminal patients. Survival of triple-negative patients was significantly short (vs. human epidermal growth factor receptor type 2-enriched patients, P < 0.001). Karnofsky performance status, HER2 status and the disease-free interval (from initial treatment to first recurrence) were shown to be significant prognostic factors (Karnofsky performance status < 70: relative risk 2.08, P = 0.028; HER2+: relative risk 2.911, P = 0.004; disease-free interval < 24 months: relative risk 1.933, P = 0.011). Breast cancer-specific Graded Prognostic Assessment scores reflected disease-free intervals and survival times. Our data indicate that breast cancer-specific Graded Prognostic Assessment-based prediction will be helpful in determining appropriate therapeutic strategies for patients with brain metastasis from breast cancer. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
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.
Shoji, Fumihiro; Haratake, Naoki; Akamine, Takaki; Takamori, Shinkichi; Katsura, Masakazu; Takada, Kazuki; Toyokawa, Gouji; Okamoto, Tatsuro; Maehara, Yoshihiko
2017-02-01
The prognostic Controlling Nutritional Status (CONUT) score is used to evaluate immuno-nutritional conditions and is a predictive factor of postoperative survival in patients with digestive tract cancer. We retrospectively analyzed clinicopathological features of patients with pathological stage I non-small cell lung cancer (NSCLC) to identify predictors or prognostic factors of postoperative survival and to investigate the role of preoperative CONUT score in predicting survival. We selected 138 consecutive patients with pathological stage I NSCLC treated from August 2005 to August 2010. We measured their preoperative CONUT score in uni- and multivariate Cox regression analyses of postoperative survival. A high CONUT score was positively associated with preoperative serum carcinoembryonic antigen level (p=0.0100) and postoperative recurrence (p=0.0767). In multivariate analysis, the preoperative CONUT score [relative risk (RR)=6.058; 95% confidence interval (CI)=1.068-113.941; p=0.0407), increasing age (RR=7.858; 95% CI=2.034-36.185; p=0.0029), and pleural invasion (RR=36.615; 95% CI=5.900-362.620; p<0.0001) were independent prognostic factors. In Kaplan-Meier analysis of recurrence-free survival (RFS), cancer-specific survival (CS), and overall survival (OS), the group with high CONUT score had a significantly shorter RFS, CS, and OS than did the low-CONUT score group by log-rank test (p=0.0458, p=0.0104 and p=0.0096, respectively). The preoperative CONUT score is both a predictive and prognostic factor in patients with pathological stage I NSCLC. This immuno-nutritional score can indicate patients at high risk of postoperative recurrence and death. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
Yamashita, Shimpei; Kohjimoto, Yasuo; Iguchi, Takashi; Koike, Hiroyuki; Kusumoto, Hiroki; Iba, Akinori; Kikkawa, Kazuro; Kodama, Yoshiki; Matsumura, Nagahide; Hara, Isao
2016-03-22
While novel drugs have been developed, docetaxel remains one of the standard initial systemic therapies for castration-resistant prostate cancer (CRPC) patients. Despite the excellent anti-tumor effect of docetaxel, its severe adverse effects sometimes distress patients. Therefore, it would be very helpful to predict the efficacy of docetaxel before treatment. The aims of this study were to evaluate the potential value of patient characteristics in predicting overall survival (OS) and to develop a risk classification for CRPC patients treated with docetaxel-based chemotherapy. This study included 79 patients with CRPC treated with docetaxel. The variables, including patient characteristics at diagnosis and at the start of chemotherapy, were retrospectively collected. Prognostic factors predicting OS were analyzed using the Cox proportional hazard model. Risk stratification for overall survival was determined based on the results of multivariate analysis. PSA response ≥50 % was observed in 55 (69.6 %) of all patients, and the median OS was 22.5 months. The multivariate analysis showed that age, serum PSA level at the start of chemotherapy, and Hb were independent prognostic factors for OS. In addition, ECOG performance status (PS) and the CRP-to-albumin ratio were not significant but were considered possible predictors for OS. Risk stratification according to the number of these risk factors could effectively stratify CRPC patients treated with docetaxel in terms of OS. Age, serum PSA level at the start of chemotherapy, and Hb were identified as independent prognostic factors of OS. ECOG PS and the CRP-to-albumin ratio were not significant, but were considered possible predictors for OS in Japanese CRPC patients treated with docetaxel. Risk stratification based on these factors could be helpful for estimating overall survival.
Lymphopenia predicts poor prognosis in patients with esophageal squamous cell carcinoma.
Feng, Ji-Feng; Liu, Jin-Shi; Huang, Ying
2014-12-01
Lymphopenia is a useful predictive factor in several cancers. The aim of this study was to determine the prognostic value of lymphopenia in patients with esophageal squamous cell carcinoma (ESCC).A retrospective analysis of 307 consecutive patients who had undergone esophagectomy for ESCC was conducted. In our study, a lymphocyte count (LC) of fewer than 1.0 Giga/L was defined as lymphopenia. Kaplan-Meier method was used to calculate the cancer-specific survival (CSS). Cox regression analyses were performed to evaluate the prognostic factors. Receiver operating characteristic (ROC) curve was also plotted to verify the accuracy of LC for CSS prediction.The mean LC was 1.55 ± 0.64 Giga/L (range 0.4-3.7 Giga/L). The incidence of lymphopenia (LC < 1.0 Giga/L) was 16.6% (51/307). Patients with lymphopenia (LC < 1.0 Giga/L) had a significantly shorter 5-year CSS (21.6% vs 43.8%, P = 0.004). On multivariate analysis, lymphopenia (LC < 1.0 Giga/L) was an independent prognostic factor in patients with ESCC (P = 0.013). Lymphopenia had a hazard ratio (HR) of 1.579 [95% confidence interval (CI): 1.100-2.265] for CSS. ROC curve demonstrated that lymphopenia (LC < 1.0 Giga/L) predicts survival with a sensitivity of 86.2% and a specificity of 27.2%. Lymphopenia (LC < 1.0 Giga/L) is still an independent predictive factor for long-term survival in patients with ESCC.
Long-term Outcome of Chondrosarcoma: A Single Institutional Experience.
Bindiganavile, Srimanth; Han, Ilkyu; Yun, Ji Yeon; Kim, Han-Soo
2015-10-01
The prognostic factors of chondrosarcoma remain uncertain as only a few large studies with long-term follow-up have been reported. The aim of this study was to analyze oncological outcomes and prognostic factors. A retrospective review of oncological outcomes and prognostic factors was performed on 125 consecutive chondrosarcoma patients who underwent surgery at our institution. Overall survival was 91.6%±2.5%, 84.1%±3.8%, and 84.1%±3.8% at 5, 10, and 15 years respectively. Among the histological types, dedifferentiated type showed the worst survival (p < 0.001). As for conventional type chondrosarcoma, histologic grade and anatomical location predicted outcome, with high-grade with axial location having the worst outcome (p < 0.001). In contrast, low-grade chondrosarcoma of appendicular skeleton could be treated safely by intralesional curettage. Histological type was significantly associated with the outcome of chondrosarcoma. For the conventional type, histologic grade and anatomical location predicted outcome, with high-grade with axial location having the worst outcome.
Suh, Sang-Yeon; Choi, Youn Seon; Shim, Jae Yong; Kim, Young Sung; Yeom, Chang Hwan; Kim, Daeyoung; Park, Shin Ae; Kim, Sooa; Seo, Ji Yeon; Kim, Su Hyun; Kim, Daegyeun; Choi, Sung-Eun; Ahn, Hong-Yup
2010-02-01
The goal of this study was to develop a new, objective prognostic score (OPS) for terminally ill cancer patients based on an integrated model that includes novel objective prognostic factors. A multicenter study of 209 terminally ill cancer patients from six training hospitals in Korea were prospectively followed until death. The Cox proportional hazard model was used to adjust for the influence of clinical and laboratory variables on survival time. The OPS was calculated from the sum of partial scores obtained from seven significant predictors determined by the final model. The partial score was based on the hazard ratio of each predictor. The accuracy of the OPS was evaluated. The overall median survival was 26 days. On the multivariate analysis, reduced oral intake, resting dyspnea, low performance status, leukocytosis, elevated bilirubin, elevated creatinine, and elevated lactate dehydrogenase (LDH) were identified as poor prognostic factors. The range of OPS was from 0.0 to 7.0. For the above cutoff point of 3.0, the 3-week prediction sensitivity was 74.7%, the specificity was 76.5%, and the overall accuracy was 75.5%. We developed the new OPS, without clinician's survival estimates but including a new prognostic factor (LDH). This new instrument demonstrated accurate prediction of the 3-week survival. The OPS had acceptable accuracy in this study population (training set). Further validation is required on an independent population (testing set).
Predicting survival time in noncurative patients with advanced cancer: a prospective study in China.
Cui, Jing; Zhou, Lingjun; Wee, B; Shen, Fengping; Ma, Xiuqiang; Zhao, Jijun
2014-05-01
Accurate prediction of prognosis for cancer patients is important for good clinical decision making in therapeutic and care strategies. The application of prognostic tools and indicators could improve prediction accuracy. This study aimed to develop a new prognostic scale to predict survival time of advanced cancer patients in China. We prospectively collected items that we anticipated might influence survival time of advanced cancer patients. Participants were recruited from 12 hospitals in Shanghai, China. We collected data including demographic information, clinical symptoms and signs, and biochemical test results. Log-rank tests, Cox regression, and linear regression were performed to develop a prognostic scale. Three hundred twenty patients with advanced cancer were recruited. Fourteen prognostic factors were included in the prognostic scale: Karnofsky Performance Scale (KPS) score, pain, ascites, hydrothorax, edema, delirium, cachexia, white blood cell (WBC) count, hemoglobin, sodium, total bilirubin, direct bilirubin, aspartate aminotransferase (AST), and alkaline phosphatase (ALP) values. The score was calculated by summing the partial scores, ranging from 0 to 30. When using the cutoff points of 7-day, 30-day, 90-day, and 180-day survival time, the scores were calculated as 12, 10, 8, and 6, respectively. We propose a new prognostic scale including KPS, pain, ascites, hydrothorax, edema, delirium, cachexia, WBC count, hemoglobin, sodium, total bilirubin, direct bilirubin, AST, and ALP values, which may help guide physicians in predicting the likely survival time of cancer patients more accurately. More studies are needed to validate this scale in the future.
Monteiro de Oliveira Novaes, Jose Augusto; William, William N
2016-10-01
Oral squamous cell carcinomas represent a significant cancer burden worldwide. Unfortunately, chemoprevention strategies investigated to date have failed to produce an agent considered standard of care to prevent oral cancers. Nonetheless, recent advances in clinical trial design may streamline drug development in this setting. In this manuscript, we review some of these improvements, including risk prediction tools based on molecular markers that help select patients most suitable for chemoprevention. We also discuss the opportunities that novel preclinical models and modern molecular profiling techniques will bring to the prevention field in the near future, and propose a clinical trials framework that incorporates molecular prognostic factors, predictive markers and cancer biology as a roadmap to improve chemoprevention strategies for oral cancers.
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.
Prognostic factors and scoring system for survival in colonic perforation.
Komatsu, Shuhei; Shimomatsuya, Takumi; Nakajima, Masayuki; Amaya, Hirokazu; Kobuchi, Taketsune; Shiraishi, Susumu; Konishi, Sayuri; Ono, Susumu; Maruhashi, Kazuhiro
2005-01-01
No ideal and generally accepted prognostic factors and scoring systems exist to determine the prognosis of peritonitis associated with colonic perforation. This study was designed to investigate prognostic factors and evaluate the various scoring systems to allow identification of high-risk patients. Between 1996 and 2003, excluding iatrogenic and trauma cases, 26 consecutive patients underwent emergency operations for colorectal perforation and were selected for this retrospective study. Several clinical factors were analyzed as possible predictive factors, and APACHE II, SOFA, MPI, and MOF scores were calculated. The overall mortality was 26.9%. Compared with the survivors, non-survivors were found more frequently in Hinchey's stage III-IV, a low preoperative marker of pH, base excess (BE), and a low postoperative marker of white blood cell count, PaO2/FiO2 ratio, and renal output (24h). According to the logistic regression model, BE was a significant independent variable. Concerning the prognostic scoring systems, an APACHE II score of 19, a SOFA score of 8, an MPI score of 30, and an MOF score of 7 or more were significantly related to poor prognosis. Preoperative BE and postoperative white blood cell count were reliable prognostic factors and early classification using prognostic scoring systems at specific points in the disease process are useful to improve our understanding of the problems involved.
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.
Wang, Dong-Yu; Done, Susan J; Mc Cready, David R; Leong, Wey L
2014-07-04
Using genome-wide expression profiles of a prospective training cohort of breast cancer patients, ClinicoMolecular Triad Classification (CMTC) was recently developed to classify breast cancers into three clinically relevant groups to aid treatment decisions. CMTC was found to be both prognostic and predictive in a large external breast cancer cohort in that study. This study serves to validate the reproducibility of CMTC and its prognostic value using independent patient cohorts. An independent internal cohort (n = 284) and a new external cohort (n = 2,181) were used to validate the association of CMTC between clinicopathological factors, 12 known gene signatures, two molecular subtype classifiers, and 19 oncogenic signalling pathway activities, and to reproduce the abilities of CMTC to predict clinical outcomes of breast cancer. In addition, we also updated the outcome data of the original training cohort (n = 147). The original training cohort reached a statistically significant difference (p < 0.05) in disease-free survivals between the three CMTC groups after an additional two years of follow-up (median = 55 months). The prognostic value of the triad classification was reproduced in the second independent internal cohort and the new external validation cohort. CMTC achieved even higher prognostic significance when all available patients were analyzed (n = 4,851). Oncogenic pathways Myc, E2F1, Ras and β-catenin were again implicated in the high-risk groups. Both prospective internal cohorts and the independent external cohorts reproduced the triad classification of CMTC and its prognostic significance. CMTC is an independent prognostic predictor, and it outperformed 12 other known prognostic gene signatures, molecular subtype classifications, and all other standard prognostic clinicopathological factors. Our results support further development of CMTC portfolio into a guide for personalized breast cancer treatments.
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.
Kawano, Shingo; Komai, Yoshinobu; Ishioka, Junichiro; Sakai, Yasuyuki; Fuse, Nozomu; Ito, Masaaki; Kihara, Kazunori; Saito, Norio
2016-10-01
The aim of this study was to determine risk factors for survival after retrograde placement of ureteral stents and develop a prognostic model for advanced gastrointestinal tract (GIT: esophagus, stomach, colon and rectum) cancer patients. We examined the clinical records of 122 patients who underwent retrograde placement of a ureteral stent against malignant extrinsic ureteral obstruction. A prediction model for survival after stenting was developed. We compared its clinical usefulness with our previous model based on the results from nephrostomy cases by decision curve analysis. Median follow-up period was 201 days (8-1490) and 97 deaths occurred. The 1-year survival rate in this cohort was 29%. Based on multivariate analysis, primary site of colon origin, absence of retroperitoneal lymph node metastasis and serum albumin >3g/dL were significantly associated with a prolonged survival time. To develop a prognostic model, we divided the patients into 3 risk groups of favorable: 0-1 factors (N.=53), intermediate: 2 risk factors (N.=54), and poor: 3 risk factors (N.=15). There were significant differences in the survival profiles of these 3 risk groups (P<0.0001). Decision curve analyses revealed that the current model has a superior net benefit than our previous model for most of the examined probabilities. We have developed a novel prognostic model for GIT cancer patients who were treated with retrograde placement of a ureteral stent. The current model should help urologists and medical oncologists to predict survival in cases of malignant extrinsic ureteral obstruction.
D'Alessandro, Nicola; Tramutola, Giuseppe; Fasano, Giovanni Michele; Gilio, Francesco; Iside, Giovanni; Izzo, Maria Lucia; Loffredo, Andrea; Pici, Mariano; Pinto, Margherita; Tramontano, Salvatore; Citro, Giuseppe
2016-01-01
Definitive hypoparathyrodism (hypo-PTH) represents one of the most dangerous complication after total thyroidectomy. Partial or total lesion or accidental removal of parathyroid glands is an unpredictable adverse event, although real incidence is not well defined, such as management of this deficit. We started a prospective evaluation of patients treated with total thyroidectomy in our centre, to identify incidence of hypo-PTH, symptomatic or not, in relation to incidence of early postoperative hypocalcemia in our experience. We prospectively evaluated 177 patients treated for benign and malign pathology, measuring calcium before surgery and calcium and PTH at least three months after surgery. Postoperative hypocalcemia was observed in 37.3% of cases. Eight patients (4.5% of cohort) presented low level of PTH, at mean follow-up of 9.1 months. Positive predictive value for postoperative hypocalcemia was 12.1%, while negative predictive was 95.4%; confirming high sensitivity (100%) and low specificity (65.4%) for detecting hypo-PTH. All patients with late hypo-PTH presented hypocalcemia on early analysis, while no case with normal postoperative calcemia accounted with hypo-PTH: this may indicate calcemia as valid prognostic factor of good gland production, when is in the range. Moreover, isolated analysis is too limited to determine real predictability. Technical standardization represents the best method for prevention of hypo-PTH. Early hypocalcemia is a prognostic factor, even with a low specificity, of deficit of PTH-production. This observation must be related to other known prognostic factors. Postoperative normal calcemia should be a positive prognostic factor of an acceptable PTHfunction, supported by large cohorts. Hypocalcemia, Parathormone, Thyroidectomy.
Hebert, Jeffrey J; Koppenhaver, Shane L; Magel, John S; Fritz, Julie M
2010-01-01
Hebert JJ, Koppenhaver SL, Magel JS, Fritz JM. The relationship of transversus abdominis and lumbar multifidus activation and prognostic factors for clinical success with a stabilization exercise program: a cross-sectional study. To examine the relationship between prognostic factors for clinical success with a stabilization exercise program and lumbar multifidus (LM) and transversus abdominis (TrA) muscle activation assessed using rehabilitative ultrasound imaging (RUSI). Cross-sectional study. Outpatient physical therapy clinic. Volunteers with current low back pain (N=40). Not applicable. We examined the relationship between prognostic factors associated with clinical success with a stabilization exercise program (positive prone instability test, age <40y, aberrant movements, straight leg raise >91 degrees , presence of lumbar hypermobility) and degree of TrA and LM muscle activation assessed by RUSI. Significant univariate relationships were identified between LM muscle activation and the number of prognostic factors present (Pearson correlation coefficient [r] =-.558, P=.001), as well as the individual factors of a positive prone instability test (point biserial correlation coefficient [r(pbis)]=.376, P=.018) and segmental hypermobility (r(pbis)=.358, P=.025). The multivariate analyses indicated that after controlling for other variables, the addition of the variable "number of prognostic factors present" resulted in a significant increase in R(2) (P=.006). No significant univariate or multivariate relationships were observed between the prognostic factors and TrA muscle activation. Decreased LM muscle activation, but not TrA muscle activation, is associated with the presence of factors predictive of clinical success with a stabilization exercise program. Our findings provide researchers and clinicians with evidence regarding the construct validity of the prognostic factors examined in this study, as well as the potential clinical importance of the LM muscle as a target for stabilization exercises. Copyright (c) 2010 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.
[Prognosis of survival in advanced cancer].
de Arriba Méndez, J J
2007-01-01
Accurate prognoses are important in the care of patients with advanced cancer to assist clinicians in their decision making, and to help patients set their goals and priorities. Several studies have demonstrated that doctors are inaccurate and overly optimistic when predicting the survival of patients with advanced and terminal cancer. To improve prognostic accuracy, clinicians can use a number of factors that have proven to be associated with life expectancy: performance status, some signs and symptoms and some laboratory markers. Prognostic scores including most of the factors are also developed. Patients and their families can benefit from realistic prognostic information in a simple and empathetic manner.
A four-gene signature predicts survival in clear-cell renal-cell carcinoma.
Dai, Jun; Lu, Yuchao; Wang, Jinyu; Yang, Lili; Han, Yingyan; Wang, Ying; Yan, Dan; Ruan, Qiurong; Wang, Shaogang
2016-12-13
Clear-cell renal-cell carcinoma (ccRCC) is the most common pathological subtype of renal cell carcinoma (RCC), accounting for about 80% of RCC. In order to find potential prognostic biomarkers in ccRCC, we presented a four-gene signature to evaluate the prognosis of ccRCC. SurvExpress and immunohistochemical (IHC) staining of tissue microarrays were used to analyze the association between the four genes and the prognosis of ccRCC. Data from TCGA dataset revealed a prognostic prompt function of the four genes (PTEN, PIK3C2A, ITPA and BCL3). Further discovery suggested that the four-gene signature predicted survival better than any of the four genes alone. Moreover, IHC staining demonstrated a consistent result with TCGA, indicating that the signature was an independent prognostic factor of survival in ccRCC. Univariate and multivariate Cox proportional hazard regression analysis were conducted to verify the association of clinicopathological variables and the four genes' expression levels with survival. The results further testified that the risk (four-gene signature) was an independent prognostic factors of both Overall Survival (OS) and Disease-free Survival (DFS) (P<0.05). In conclusion, the four-gene signature was correlated with the survival of ccRCC, and therefore, may help to provide significant clinical implications for predicting the prognosis of patients.
Ozer, Erdener; Sarialioglu, Faik; Cetingoz, Riza; Yüceer, Nurullah; Cakmakci, Handan; Ozkal, Sermin; Olgun, Nur; Uysal, Kamer; Corapcioglu, Funda; Canda, Serefettin
2004-01-01
The purpose of this study was to investigate whether quantitative assessment of cytologic anaplasia and angiogenesis may predict the clinical prognosis in medulloblastoma and stratify the patients to avoid both undertreatment and overtreatment. Medulloblastomas from 23 patients belonging to the Pediatric Oncology Group were evaluated with respect to some prognostic variables, including histologic assessment of nodularity and desmoplasia, grading of anaplasia, measurement of nuclear size, mitotic cell count, quantification of angiogenesis, including vascular surface density (VSD) and microvessel number (NVES), and immunohistochemical scoring of vascular endothelial growth factor (VEGF) expression. Univariate and multivariate analyses for prognostic indicators for survival were performed. Univariate analysis revealed that extensive nodularity was a significant favorable prognostic factor, whereas the presence of anaplasia, increased nuclear size, mitotic rate, VSD, and NVES were significant unfavorable prognostic factors. Using multivariate analysis, increased nuclear size was found to be an independent unfavorable prognostic factor for survival. Neither the presence of desmoplasia nor VEGF expression was significantly related to patient survival. Although care must be taken not to overstate the importance of the results of this single-institution preliminary report, pathologic grading of medulloblastomas with respect to grading of anaplasia and quantification of nodularity, nuclear size, and microvessel profiles may be clinically useful for the treatment of medulloblastomas. Further validation of the independent prognostic significance of nuclear size in stratifying patients is required.
Zhou, Zhi-Rui; Wang, Chen-Chen; Sun, Xiang-Jie; Yang, Zhao-Zhi; Chen, Xing-Xing; Shao, Zhi-Ming; Yu, Xiao-Li; Guo, Xiao-Mao
2018-04-01
The aim of this study was to explore the independent prognostic factors related to postoperative recurrence-free survival (RFS) in patients with breast phyllodes tumors (PTBs). A retrospective analysis was conducted in Fudan University Shanghai Cancer Center. According to histological type, patients with benign PTBs were classified as a low-risk group, while borderline and malignant PTBs were classified as a high-risk group. The Cox regression model was adopted to identify factors affecting postoperative RFS in the two groups, and a nomogram was generated to predict recurrence-free survival at 1, 3, and 5 years. Among the 404 patients, 168 (41.6%) patients had benign PTB, 184 (45.5%) had borderline PTB, and 52 (12.9%) had malignant PTB. Fifty-five patients experienced postoperative local recurrence, including six benign cases, 26 borderline cases, and 22 malignant cases; the three histological types of PTB had local recurrence rates of 3.6%, 14.1%, and 42.3%, respectively. Stromal cell atypia was an independent prognostic factor for RFS in the low-risk group, while the surgical approach and tumor border were independent prognostic factors for RFS in the high-risk group, and patients receiving simple excision with an infiltrative tumor border had a higher recurrence rate. A nomogram developed based on clinicopathologic features and surgical approaches could predict recurrence-free survival at 1, 3, and 5 years. For high-risk patients, this predictive nomogram based on tumor border, tumor residue, mitotic activity, degree of stromal cell hyperplasia, and atypia can be applied for patient counseling and clinical management. The efficacy of adjuvant radiotherapy remains uncertain. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
Azumi, Motoi; Suda, Takeshi; Terai, Shuji; Akazawa, Kouhei
2017-01-01
Objective Radiofrequency ablation has been used widely for the local ablation of hepatocellular carcinoma, particularly in its early stages. The study aim was to identify significant prognostic factors and develop a predictive nomogram for patients with hepatocellular carcinoma who have undergone radiofrequency ablation. We also developed the formula to predict the probability of 3- and 5-year overall survival based on clinical variables. Methods We retrospectively studied 96 consecutive patients with hepatocellular carcinoma who had undergone radiofrequency ablation as a first-line treatment. Independent and significant factors affecting the overall survival were selected using a Cox proportional hazards model, and a prognostic nomogram was developed based on these factors. The predictive accuracy of the nomogram was determined by Harrell's concordance index and compared with the Cancer of the Liver Italian Program score and Japan Integrated Staging score. Results A multivariate analysis revealed that age, indocyanine green plasma disappearance rate, and log(des-gamma-carboxy prothrombin) level were independent and significant factors influencing the overall survival. The nomogram was based on these three factors. The mean concordance index of the nomogram was 0.74±0.08, which was significantly better than that of conventional staging systems using the Cancer of the Liver Italian Program score (0.54±0.03) and Japan Integrated Staging score (0.59±0.07). Conclusion This study suggested that the indocyanine green plasma disappearance rate and age at radiofrequency ablation (RFA) and des-gamma-carboxy-prothrombin (DCP) are good predictors of the prognosis in hepatocellular carcinoma patients after radiofrequency ablation. We successfully developed a nomogram using obtainable variables before treatment. PMID:28458303
Azumi, Motoi; Suda, Takeshi; Terai, Shuji; Akazawa, Kouhei
2017-01-01
Objective Radiofrequency ablation has been used widely for the local ablation of hepatocellular carcinoma, particularly in its early stages. The study aim was to identify significant prognostic factors and develop a predictive nomogram for patients with hepatocellular carcinoma who have undergone radiofrequency ablation. We also developed the formula to predict the probability of 3- and 5-year overall survival based on clinical variables. Methods We retrospectively studied 96 consecutive patients with hepatocellular carcinoma who had undergone radiofrequency ablation as a first-line treatment. Independent and significant factors affecting the overall survival were selected using a Cox proportional hazards model, and a prognostic nomogram was developed based on these factors. The predictive accuracy of the nomogram was determined by Harrell's concordance index and compared with the Cancer of the Liver Italian Program score and Japan Integrated Staging score. Results A multivariate analysis revealed that age, indocyanine green plasma disappearance rate, and log (des-gamma-carboxy prothrombin) level were independent and significant factors influencing the overall survival. The nomogram was based on these three factors. The mean concordance index of the nomogram was 0.74±0.08, which was significantly better than that of conventional staging systems using the Cancer of the Liver Italian Program score (0.54±0.03) and Japan Integrated Staging score (0.59±0.07). Conclusion This study suggested that the indocyanine green plasma disappearance rate and age at radiofrequency ablation (RFA) and des-gamma-carboxy-prothrombin (DCP) are good predictors of the prognosis in hepatocellular carcinoma patients after radiofrequency ablation. We successfully developed a nomogram using obtainable variables before treatment.
Vermaat, J S; van der Tweel, I; Mehra, N; Sleijfer, S; Haanen, J B; Roodhart, J M; Engwegen, J Y; Korse, C M; Langenberg, M H; Kruit, W; Groenewegen, G; Giles, R H; Schellens, J H; Beijnen, J H; Voest, E E
2010-07-01
In metastatic renal cell cancer (mRCC), the Memorial Sloan-Kettering Cancer Center (MSKCC) risk model is widely used for clinical trial design and patient management. To improve prognostication, we applied proteomics to identify novel serological proteins associated with overall survival (OS). Sera from 114 mRCC patients were screened by surface-enhanced laser desorption ionization time-of-flight mass spectrometry (SELDI-TOF MS). Identified proteins were related to OS. Three proteins were subsequently validated with enzyme-linked immunosorbent assays and immunoturbidimetry. Prognostic models were statistically bootstrapped to correct for overestimation. SELDI-TOF MS detected 10 proteins associated with OS. Of these, apolipoprotein A2 (ApoA2), serum amyloid alpha (SAA) and transthyretin were validated for their association with OS (P = 5.5 x 10(-9), P = 1.1 x 10(-7) and P = 0.0004, respectively). Combining ApoA2 and SAA yielded a prognostic two-protein signature [Akaike's Information Criteria (AIC) = 732, P = 5.2 x 10(-7)]. Including previously identified prognostic factors, multivariable Cox regression analysis revealed ApoA2, SAA, lactate dehydrogenase, performance status and number of metastasis sites as independent factors for survival. Using these five factors, categorization of patients into three risk groups generated a novel protein-based model predicting patient prognosis (AIC = 713, P = 4.3 x 10(-11)) more robustly than the MSKCC model (AIC = 729, P = 1.3 x 10(-7)). Applying this protein-based model instead of the MSKCC model would have changed the risk group in 38% of the patients. Proteomics and subsequent validation yielded two novel prognostic markers and survival models which improved prediction of OS in mRCC patients over commonly used risk models. Implementation of these models has the potential to improve current risk stratification, although prospective validation will still be necessary.
NASA Technical Reports Server (NTRS)
Goebel, Kai; Vachtsevanos, George; Orchard, Marcos E.
2013-01-01
Knowledge discovery, statistical learning, and more specifically an understanding of the system evolution in time when it undergoes undesirable fault conditions, are critical for an adequate implementation of successful prognostic systems. Prognosis may be understood as the generation of long-term predictions describing the evolution in time of a particular signal of interest or fault indicator, with the purpose of estimating the remaining useful life (RUL) of a failing component/subsystem. Predictions are made using a thorough understanding of the underlying processes and factor in the anticipated future usage.
Markers of systemic inflammation predict survival in patients with advanced renal cell cancer.
Fox, P; Hudson, M; Brown, C; Lord, S; Gebski, V; De Souza, P; Lee, C K
2013-07-09
The host inflammatory response has a vital role in carcinogenesis and tumour progression. We examined the prognostic value of inflammatory markers (albumin, white-cell count and its components, and platelets) in pre-treated patients with advanced renal cell carcinoma (RCC). Using data from a randomised trial, multivariable proportional hazards models were generated to examine the impact of inflammatory markers and established prognostic factors (performance status, calcium, and haemoglobin) on overall survival (OS). We evaluated a new prognostic classification incorporating additional information from inflammatory markers. Of the 416 patients, 362 were included in the analysis. Elevated neutrophil counts, elevated platelet counts, and a high neutrophil-lymphocyte ratio were significant independent predictors for shorter OS in a model with established prognostic factors. The addition of inflammatory markers improves the discriminatory value of the prognostic classification as compared with established factors alone (C-statistic 0.673 vs 0.654, P=0.002 for the difference), with 25.8% (P=0.004) of patients more appropriately classified using the new classification. Markers of systemic inflammation contribute significantly to prognostic classification in addition to established factors for pre-treated patients with advanced RCC. Upon validation of these data in independent studies, stratification of patients using these markers in future clinical trials is recommended.
Circulating tumor cells and miRNAs as prognostic markers in neuroendocrine neoplasms.
Zatelli, Maria Chiara; Grossrubatscher, Erika Maria; Guadagno, Elia; Sciammarella, Concetta; Faggiano, Antongiulio; Colao, Annamaria
2017-06-01
The prognosis of neuroendocrine neoplasms (NENs) is widely variable and has been shown to associate with several tissue- and blood-based biomarkers in different settings. The identification of prognostic factors predicting NEN outcome is of paramount importance to select the best clinical management for these patients. Prognostic markers have been intensively investigated, also taking advantage of the most modern techniques, in the perspective of personalized medicine and appropriate resource utilization. This review summarizes the available data on the possible role of circulating tumor cells and microRNAs as prognostic markers in NENs. © 2017 Society for Endocrinology.
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.
Prognostic factors for early severity in a childhood multiple sclerosis cohort.
Mikaeloff, Yann; Caridade, Guillaume; Assi, Saada; Suissa, Samy; Tardieu, Marc
2006-09-01
The goal was to identify prognostic factors for an early severe course in a cohort of patients with childhood-onset multiple sclerosis, for the construction of a predictive tool. The cohort consisted of 197 children from the French Kid Sclérose en Plaques neuropediatric cohort with relapsing/remitting multiple sclerosis beginning before the age of 16 years. Patients were included from 1990 to 2003. We used multivariate survival analysis (Cox model) to evaluate the prognostic value of clinical, MRI, and biological covariates at onset for the occurrence of a third attack or severe disability ("severity" outcome). The cohort was monitored for a mean of 5.5 +/- 3.6 years. The "severity" outcome was recorded for 144 patients (73%). The risk of severity was higher for girls, for a time between the first and second attacks of < 1 year, for childhood-onset multiple sclerosis MRI criteria at onset, for an absence of severe mental state changes at onset, and for a progressive course. A derived childhood-onset multiple sclerosis potential index for early severity was found to have a positive predictive value for severity of > 35% for the upper 2 quartiles. The clinical and MRI prognostic factors for early severity that were identified were used as the basis of a predictive tool, which will be validated in another cohort. This tool should make it possible to identify subgroups at risk of early severe disease and should facilitate therapeutic studies.
New prognostic factors and scoring system for patients with skeletal metastasis.
Katagiri, Hirohisa; Okada, Rieko; Takagi, Tatsuya; Takahashi, Mitsuru; Murata, Hideki; Harada, Hideyuki; Nishimura, Tetsuo; Asakura, Hirofumi; Ogawa, Hirofumi
2014-10-01
The aim of this study was to update a previous scoring system for patients with skeletal metastases, that was proposed by Katagiri et al. in 2005, by introducing a new factor (laboratory data) and analyzing a new patient cohort. Between January 2005 and January 2008, we treated 808 patients with symptomatic skeletal metastases. They were prospectively registered regardless of their treatments, and the last follow-up evaluation was performed in 2012. There were 441 male and 367 female patients with a median age of 64 years. Of these patients, 749 were treated nonsurgically while the remaining 59 underwent surgery for skeletal metastasis. A multivariate analysis was conducted using the Cox proportional hazards model. We identified six significant prognostic factors for survival, namely, the primary lesion, visceral or cerebral metastases, abnormal laboratory data, poor performance status, previous chemotherapy, and multiple skeletal metastases. The first three factors had a larger impact than the remaining three. The prognostic score was calculated by adding together all the scores for individual factors. With a prognostic score of ≥7, the survival rate was 27% at 6 months, and only 6% at 1 year. In contrast, patients with a prognostic score of ≤3 had a survival rate of 91% at 1 year, and 78% at 2 years. Comparing the revised system with the previous one, there was a significantly lower number of wrongly predicted patients using the revised system. This revised scoring system was able to predict the survival rates of patients with skeletal metastases more accurately than the previous system and may be useful for selecting an optimal treatment. © 2014 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
Big genomics and clinical data analytics strategies for precision cancer prognosis.
Ow, Ghim Siong; Kuznetsov, Vladimir A
2016-11-07
The field of personalized and precise medicine in the era of big data analytics is growing rapidly. Previously, we proposed our model of patient classification termed Prognostic Signature Vector Matching (PSVM) and identified a 37 variable signature comprising 36 let-7b associated prognostic significant mRNAs and the age risk factor that stratified large high-grade serous ovarian cancer patient cohorts into three survival-significant risk groups. Here, we investigated the predictive performance of PSVM via optimization of the prognostic variable weights, which represent the relative importance of one prognostic variable over the others. In addition, we compared several multivariate prognostic models based on PSVM with classical machine learning techniques such as K-nearest-neighbor, support vector machine, random forest, neural networks and logistic regression. Our results revealed that negative log-rank p-values provides more robust weight values as opposed to the use of other quantities such as hazard ratios, fold change, or a combination of those factors. PSVM, together with the classical machine learning classifiers were combined in an ensemble (multi-test) voting system, which collectively provides a more precise and reproducible patient stratification. The use of the multi-test system approach, rather than the search for the ideal classification/prediction method, might help to address limitations of the individual classification algorithm in specific situation.
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
Visentin, Andrea; Facco, Monica; Frezzato, Federica; Castelli, Monica; Trimarco, Valentina; Martini, Veronica; Gattazzo, Cristina; Severin, Filippo; Chiodin, Giorgia; Martines, Annalisa; Bonaldi, Laura; Gianesello, Ilaria; Pagnin, Elisa; Boscaro, Elisa; Piazza, Francesco; Zambello, Renato; Semenzato, Gianpietro; Trentin, Livio
2015-10-01
Several prognostic factors have been identified to predict the outcome of patients with chronic lymphocytic leukemia (CLL), but only a few studies analyzed more markers together. Taking advantage of a population of 608 patients, we identified the strongest prognostic markers of survival and, subsequently, in a cohort of 212 patients we integrated data of cytogenetic lesions, IGHV mutational status, and CD38 expression in a new and easy scoring system we called the integrated CLL scoring system (ICSS). ICSS defines 3 groups of risk: (1) low risk (patients with 13q(-) or normal fluorescence in-situ hybridization analysis results, mutated IGHV, and CD38) (2) high risk (all 11q(-) or 17p(-) patients and/or all unmutated IGHV and CD38(+) patients); and (3) intermediate risk (all remaining patients). Using only these 3 already available prognostic factors, we were able to properly redefine patients and better predict the clinical course of the disease. ICSS could become a useful tool for CLL patients' management. Copyright © 2015 Elsevier Inc. All rights reserved.
Molecular Pathogenesis and Diagnostic, Prognostic and Predictive Molecular Markers in Sarcoma.
Mariño-Enríquez, Adrián; Bovée, Judith V M G
2016-09-01
Sarcomas are infrequent mesenchymal neoplasms characterized by notable morphological and molecular heterogeneity. Molecular studies in sarcoma provide refinements to morphologic classification, and contribute diagnostic information (frequently), prognostic stratification (rarely) and predict therapeutic response (occasionally). Herein, we summarize the major molecular mechanisms underlying sarcoma pathogenesis and present clinically useful diagnostic, prognostic and predictive molecular markers for sarcoma. Five major molecular alterations are discussed, illustrated with representative sarcoma types, including 1. the presence of chimeric transcription factors, in vascular tumors; 2. abnormal kinase signaling, in gastrointestinal stromal tumor; 3. epigenetic deregulation, in chondrosarcoma, chondroblastoma, and other tumors; 4. deregulated cell survival and proliferation, due to focal copy number alterations, in dedifferentiated liposarcoma; 5. extreme genomic instability, in conventional osteosarcoma as a representative example of sarcomas with highly complex karyotype. Copyright © 2016 Elsevier Inc. All rights reserved.
Prognostic factors in multiple myeloma: selection using Cox's proportional hazard model.
Pasqualetti, P; Collacciani, A; Maccarone, C; Casale, R
1996-01-01
The pretreatment characteristics of 210 patients with multiple myeloma, observed between 1980 and 1994, were evaluated as potential prognostic factors for survival. Multivariate analysis according to Cox's proportional hazard model identified in the 160 dead patients with myeloma, among 26 different single prognostic variables, the following factors in order of importance: beta 2-microglobulin; bone marrow plasma cell percentage, hemoglobinemia, degree of lytic bone lesions, serum creatinine, and serum albumin. By analysis of these variables a prognostic index (PI), that considers the regression coefficients derived by Cox's model of all significant factors, was obtained. Using this it was possible to separate the whole patient group into three stages: stage I (PI < 1.485, 67 patients), stage II (PI: 1.485-2.090, 76 patients), and stage III (PI > 2.090, 67 patients), with a median survivals of 68, 36 and 13 months (P < 0.0001), respectively. Also the responses to therapy (P < 0.0001) and the survival curves (P < 0.00001) presented significant differences among the three subgroups. Knowledge of these factors could be of value in predicting prognosis and in planning therapy in patients with multiple myeloma.
Osteosarcoma: Diagnostic dilemmas in histopathology and prognostic factors
Wadhwa, Neelam
2014-01-01
Osteosarcoma (OS), the commonest malignancy of osteoarticular origin, is a very aggressive neoplasm. Divergent histologic differentiation is common in OS; hence triple diagnostic approach is essential in all cases. 20% cases are atypical owing to lack of concurrence among clinicoradiologic and pathologic features necessitating resampling. Recognition of specific anatomic and histologic variants is essential in view of better outcome. Traditional prognostic factors of OS do stratify patients for short term outcome, but often fail to predict their long term outcome. Considering the negligible improvement in the patient outcome during the last 20 years, search for novel prognostic factors is in progress like ezrin vascular endothelial growth factor, chemokine receptors, dysregulation of various micro ribonucleic acid are potentially promising. Their utility needs to be validated by long term followup studies before they are incorporated in routine clinical practice. PMID:24932029
Shi, Qiyun; Sinden, Kathryn; MacDermid, Joy C; Walton, David; Grewal, Ruby
2014-01-01
Systematic review. Traumatic hand injuries are frequent cause of work related injuries and can result in prolonged durations of time loss from work. To systematically review available evidence to determine which prognostic factors predict return-to-work (RTW) following work-related traumatic hand injuries. We searched Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL and PsycINFO from 1980 to September 2013 and reference lists of articles. Studies investigating any prognostic factors of RTW after traumatic hand injury were included. Two reviewers performed study selection, assessment of methodological quality and data extraction independently of each other. Identified factors were grouped into conceptual prognostic factor categories. We assessed 8 studies, which addressed 11 potential prognostic factors (i.e., sociodemographic factors, occupation, work compensation status, treatment related factors, impairment severity, location of injury, etc.). The quality of the studies was low to moderate. Across all included studies, RTW (original or modified work) occurred in over 60% of individuals by 6 months. There was consistent low-moderate quality evidence that individuals with more severe impairments and lower pre-injury income were less likely to RTW, and low-moderate quality evidence that age, gender and level of education had no impact on RTW. Evidence on other commonly cited prognostic factors were limited in the literature. Impairment severity and lower pre-injury income showed a consistent association with RTW following occupational hand injury, while other factors demonstrated no or variable effects across studies. Additional high-quality studies are warranted toward improving our understanding of the complex factors that mediate RTW following a traumatic work-related hand injury. 2a. Copyright © 2014 Hanley & Belfus. Published by Elsevier Inc. All rights reserved.
Auclin, Edouard; Bourillon, Camille; De Maio, Eleonora; By, Marie Agnes; Seddik, Sofiane; Fournier, Laure; Auvray, Marie; Dautruche, Antoine; Vano, Yann-Alexandre; Thibault, Constance; Joly, Florence; Brunereau, Laurent; Gomez-Roca, Carlos; Chevreau, Christine; Elaidi, Reza; Oudard, Stéphane
2017-06-01
The objective of the study was to assess the prognostic role of skeletal muscle index (SMI) in metastatic renal cell carcinoma (mRCC) patients treated with everolimus, and its effect of on everolimus-induced toxicity. Consecutive mRCC patients treated with everolimus between February 2007 and November 2014 underwent computed tomography scans at a single center performed by the same radiologist. SMI was assessed before everolimus treatment using the L3 cross-sectional area. Overall survival (OS) was analyzed according to SMI value. Results were adjusted using the International Metastatic Database Consortium (IMDC) prognostic group, body mass index (BMI), and/or number of previous tyrosine kinase inhibitor lines (NPL). One hundred twenty-four mRCC patients (mean age, 60.21 years) were treated with everolimus as second- or third-line (82.3%) or > third-line (17.7%) therapy. Most patients (87.9%) had clear cell carcinoma. IMDC prognostic group was "favorable" (32.3%), "intermediate" (50%), or "poor" (17.7%). Median SMI was 40.75. OS was longer in patients from the highest versus lowest SMI tercile: 21.9 versus 10 months (P = .002). Continuous SMI at baseline was not significantly associated with OS after adjustment for IMDC prognostic group, BMI, or NPL but the highest versus lowest SMI tercile was an independent prognostic factor in multivariate analysis (P = .025). There was no difference in everolimus toxicity between SMI tercile groups. SMI was an independent prognostic factor for mRCC patients treated with everolimus. Whether this provides additional prognostic value to IMDC criteria needs to be confirmed in a larger cohort. SMI does not seem to be predictive of everolimus-induced toxicity. Copyright © 2017 Elsevier Inc. All rights reserved.
Baltruškevičienė, Edita; Mickys, Ugnius; Žvirblis, Tadas; Stulpinas, Rokas; Pipirienė Želvienė, Teresė; Aleknavičius, Eduardas
2016-01-01
Background. KRAS mutation is an important predictive and prognostic factor for patients receiving anti-EGFR therapy. An expanded KRAS, NRAS, BRAF, PIK3CA mutation analysis provides additional prognostic information, but its role in predicting bevacizumab efficacy is unclear. The aim of our study was to evaluate the incidence of KRAS, NRAS, BRAF and PIK3CA mutations in metastatic colorectal cancer patients receiving first line oxaliplatin based chemotherapy with or without bevacizumab and to evaluate their prognostic and predictive significance. Methods. 55 patients with the first-time diagnosed CRC receiving FOLFOX ± bevacizumab were involved in the study. Tumour blocks were tested for KRAS mutations in exons 2, 3 and 4, NRAS mutations in exons 2, 3 and 4, BRAF mutation in exon 15 and PIK3CA mutations in exons 9 and 20. The association between mutations and clinico-pathological factors, treatment outcomes and survival was analyzed. Results. KRAS mutations were detected in 67.3% of the patients, BRAF in 1.8%, PIK3CA in 5.5% and there were no NRAS mutations. A significant association between the high CA 19–9 level and KRAS mutation was detected (mean CA 19–9 levels were 276 and 87 kIU/l, respectively, p = 0.019). There was a significantly higher response rate in the KRAS, NRAS, BRAF and PIK3CA wild type cohort receiving bevacizumab compared to any gene mutant type (100 and 60%, respectively, p = 0.030). The univariate Cox regression analysis did not confirm KRAS and other tested mutations as prognostic factors for PFS or OS. Conclusions. Our study revealed higher KRAS and lower NRAS, BRAF and PIK3CA mutation rates in the Lithuanian population than those reported in the literature. KRAS mutation was associated with the high CA 19–9 level and mucinous histology type, but did not show any predictive or prognostic significance. The expanded KRAS, NRAS, BRAF and PIK3CA mutation analysis provided additional significant predictive information. PMID:28356789
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.
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.
Eskiizmir, G; Ozgur, E; Karaca, G; Temiz, P; Yanar, N Hacioglu; Ozyurt, B Cengiz
2017-10-01
To determine the locoregional control and survival rates (in terms of risk factors) of patients who underwent surgical resection of early-stage lip cancer and for whom a 'wait and see' policy in terms of neck status had been implemented. The sociodemographic data, tumour stage, tumour characteristics and histopathological features of 41 patients with early-stage lip cancer were evaluated. Factors predictive of survival and locoregional recurrence were analysed. The five-year overall survival and disease-free survival rates were determined, and the prognostic risk factors were compared. The mean follow-up period was 60.5 months (range, 4-92 months). Age, sex, tumour stage, tumour thickness and volume, and perineural involvement were not predictive of locoregional recurrence or survival. Pathological tumour stage (T1 vs T2) was a prognostic factor for both five-year overall survival (87.3 vs 65.6 per cent, p = 0.042) and disease-free survival (88.6 vs 65.6 per cent, p = 0.037). Tumour stage was clearly a major factor affecting the prognosis of surgically treated patients with early-stage lip cancer for whom a 'wait and see' policy in terms of neck status had been implemented.
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
Adult medulloblastoma: clinical characters, prognostic factors, outcomes and patterns of relapse.
Zhang, Na; Ouyang, Taohui; Kang, Huicong; Long, Wang; Thomas, Benjamin; Zhu, Suiqiang
2015-09-01
To analyze the clinical characters, prognostic factors, patterns of relapse and treatment outcomes for medulloblastoma in adults. The clinical materials of 73 consecutive adult patients (age, ≥16 years) with medulloblastoma were analyzed retrospectively. Follow-up data were available in 62 patients, ranging from 10 to 142 months (median, 78.4 months). Outcome in survival was assessed by the progression-free survival (PFS) and overall survival (OS). Univariate and multivariate analysis were performed to determine the prognostic factors. Total or near-total tumor resection was achieved in 37 cases (59.7 %), subtotal in 19 cases (30.6 %), and partial resection in 6 cases (9.7 %).Twenty-two patients experienced recurrences, and 45 % percent of all recurrences occurred more than 4 years after initial surgery. The PFS rates at 5 and 8 years were 60.1 and 37.0 %, respectively. The OS rates at 5 and 8 years were 82.6 and 57.3 %, respectively. In univariate analysis, less tumor resection, non-desmoplastic pathology, and brainstem involvement were risk factors for worse PFS and OS (P < 0.05). High-risk category was associated with just lower PFS, but not OS. In multivariate analysis, complete resection and desmoplastic pathology were independently predictive factors of improved PFS and OS. In adult medulloblastoma, late relapse is common and therefore long-term follow-up is important for evaluating the real impact of treatments. Risk category had prognostic value just for PFS, but not for OS. Complete resection and desmoplastic histology are independently predictive factors for favorable outcomes.
Prognostic factors in patients with spinal metastasis: a systematic review and meta-analysis.
Luksanapruksa, Panya; Buchowski, Jacob M; Hotchkiss, William; Tongsai, Sasima; Wilartratsami, Sirichai; Chotivichit, Areesak
2017-05-01
Incidence of symptomatic spinal metastasis has increased owing to improvement in treatment of the disease. One of the key factors that influences decision-making is expected patient survival. To our knowledge, no systematic reviews or meta-analysis have been conducted that review independent prognostic factors in spinal metastases. This study aimed to determine independent prognostic factors that affect outcome in patients with metastatic spine disease. This is a systematic literature review and meta-analysis of publications for prognostic factors in spinal metastatic disease. Pooled patient results from cohort and observational studies. Meta-analysis for poor prognostic factors as determined by hazard ratio (HR) and 95% confidential interval (95% CI). We systematically searched relevant publications in PubMed and Embase. The following search terms were used: ("'spinal metastases'" OR "'vertebral metastases'" OR "spinal metastasis" OR 'vertebral metastases') AND ('"prognostic factors"' OR "'survival'"). Inclusion criteria were prospective and retrospective cohort series that report HR and 95% CI of independent prognostic factors from multivariate analysis. Two reviewers independently assessed all papers. The quality of included papers was assessed by using Newcastle-Ottawa Scale for cohort studies and publication bias was assessed by using funnel plot, Begg test, and Egger test. The prognostic factors that were mentioned in at least three publications were pooled. Meta-analysis was performed using HR and 95% CI as the primary outcomes of interest. Heterogeneity was assessed using the I 2 method. A total of 3,959 abstracts (1,382 from PubMed and 2,577 from Embase) were identified through database search and 40 publications were identified through review of cited publications. The reviewers selected a total of 51 studies for qualitative synthesis and 43 studies for meta-analysis. Seventeen poor prognostic factors were identified. These included presence of a neurologic deficit before surgery, non-ambulatory status before radiotherapy (RT), non-ambulatory status before surgery, presence of bone metastases, presence of multiple bone metastases (>2 sites), presence of multiple spinal metastases (>3 sites), development of motor deficit in <7 days before initiating RT, development of motor deficit in <14 days before initiating RT, time interval from cancer diagnosis to RT <15 months, Karnofsky Performance Score (KPS) 10-40, KPS 50-70, KPS<70, Eastern Cooperative Oncology Group (ECOG) grade 3-4, male gender, presence of visceral metastases, moderate growth tumor on Tomita score (TS) classification, and rapid growth tumor on TS classification. Seventeen independent poor prognostic factors were identified in this study. These can be categorized into cancer-specific and nonspecific prognostic factors. A tumor-based prognostic scoring system that combines all specific and general factors may enhance the accuracy of survival prediction in patients with metastatic spine disease. Copyright © 2016 Elsevier Inc. All rights reserved.
Next-generation prognostic assessment for diffuse large B-cell lymphoma
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.
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.
Blumenthal, James A.; Smith, Patrick J.; Durheim, Michael; Mabe, Stephanie; Emery, Charles F.; Martinu, Tereza; Diaz, Philip T.; Babyak, Michael; Welty-Wolf, Karen; Palmer, Scott
2015-01-01
Objective To examine the prognostic value of select biobehavioral factors in patients with chronic obstructive pulmonary disease (COPD) in a secondary analysis of participants from the INSPIRE-II trial. Methods Three hundred twenty six outpatients with COPD underwent assessments of pulmonary function, physical activity, body mass index, inflammation, pulmonary symptoms, depression, and pulmonary quality of life, and were followed for up to 5.4 years for subsequent clinical events. The prognostic value of each biobehavioral factor, considered individually and combined, also was examined in the context of existing Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2011 risk stratification. Results Sixty-nine individuals experienced a hospitalization or died over a mean follow-up time period of 2.4 (interquartile range = 1.6) years. GOLD classification was associated with an increased risk of clinical events (HR = 2.72 [95% CI 1.63, 4.54], per stage); Six Minute Walk (HR = 0.50 [0.34, 0.73] per 500 feet), total steps (HR = 0.82 [0.71, 0.94] per 1,000 steps), hsC-reactive protein (HR = 1.44 [1.01, 2.06] per 4.5 mg/L), depression (HR = 1.12 [1.01, 1.25] per 4 points), and pulmonary quality of life (HR = 1.73 [1.14, 2.63] per 25 points) were each predictive over and above the GOLD assessment. However, only GOLD group and Six Minute Walk were predictive of all-cause mortality and COPD hospitalization when all biobehavioral variables were included together in a multivariable model. Conclusion Biobehavioral factors provide added prognostic information over and above measures of COPD severity in predicting adverse events in patients with COPD. PMID:26780299
Bastick, Alex N; Belo, Janneke N; Runhaar, Jos; Bierma-Zeinstra, Sita M A
2015-09-01
A previous systematic review on prognostic factors for knee osteoarthritis (OA) progression showed associations for generalized OA and hyaluronic acid levels. Knee pain, radiographic severity, sex, quadriceps strength, knee injury, and regular sport activities were not associated. It has been a decade since the literature search of that review and many studies have been performed since then investigating prognostic factors for radiographic knee OA progression. The purpose of this study is to provide an updated systematic review of available evidence regarding prognostic factors for radiographic knee OA progression. We searched for observational studies in MEDLINE and EMBASE. Key words were: knee, osteoarthritis (or arthritis, or arthrosis, or degenerative joint disease), progression (or prognosis, or precipitate, or predictive), and case-control (or cohort, or longitudinal, or follow-up). Studies fulfilling the inclusion criteria were assessed for methodologic quality according to established criteria for reviews on prognostic factors in musculoskeletal disorders. Data were extracted and results were pooled if possible or summarized according to a best-evidence synthesis. A total of 1912 additional articles were identified; 43 met our inclusion criteria. The previous review contained 36 articles, thus providing a new total of 79 articles. Seventy-two of the included articles were scored high quality, the remaining seven were low quality. The pooled odds ratio (OR) of two determinants showed associations with knee OA progression: baseline knee pain (OR, 2.38 [95% CI, 1.74-3.27) and Heberden nodes (OR, 2.66 [95% CI, 1.46-8.84]). Our best-evidence synthesis showed strong evidence that varus alignment, serum hyaluronic acid, and tumor necrosis factor-α are associated with knee OA progression. There is strong evidence that sex, former knee injury, quadriceps strength, smoking, running, and regular performance of sports are not associated with knee OA progression. Evidence for the majority of determined associations, however, was limited, conflicting, or inconclusive. Baseline knee pain, presence of Heberden nodes, varus alignment, and high levels of serum markers hyaluronic acid and tumor necrosis factor-α predict knee OA progression. Sex, knee injury, and quadriceps strength, among others, did not predict knee OA progression. Large variation remains in definitions of knee OA and knee OA progression. Clinical studies should use more consistent definitions of these factors to facilitate data pooling by future meta-analyses.
2013-01-01
Background The use of restricted randomisation methods such as minimisation is increasing. This paper investigates under what conditions it is preferable to use restricted randomisation in order to achieve balance between treatment groups at baseline with regard to important prognostic factors and whether trialists should be concerned that minimisation may be considered deterministic. Methods Using minimisation as the randomisation algorithm, treatment allocation was simulated for hypothetical patients entering a theoretical study having values for prognostic factors randomly assigned with a stipulated probability. The number of times the allocation could have been determined with certainty and the imbalances which might occur following randomisation using minimisation were examined. Results Overall treatment balance is relatively unaffected by reducing the probability of allocation to optimal treatment group (P) but within-variable balance can be affected by any P <1. This effect is magnified by increased numbers of prognostic variables, the number of categories within them and the prevalence of these categories within the study population. Conclusions In general, for smaller trials, probability of treatment allocation to the treatment group with fewer numbers requires a larger value P to keep treatment and variable groups balanced. For larger trials probability of allocation values from P = 0.5 to P = 0.8 can be used while still maintaining balance. For one prognostic variable there is no significant benefit in terms of predictability in reducing the value of P. However, for more than one prognostic variable, significant reduction in levels of predictability can be achieved with the appropriate choice of P for the given trial design. PMID:23537389
McPherson, Gladys C; Campbell, Marion K; Elbourne, Diana R
2013-03-27
The use of restricted randomisation methods such as minimisation is increasing. This paper investigates under what conditions it is preferable to use restricted randomisation in order to achieve balance between treatment groups at baseline with regard to important prognostic factors and whether trialists should be concerned that minimisation may be considered deterministic. Using minimisation as the randomisation algorithm, treatment allocation was simulated for hypothetical patients entering a theoretical study having values for prognostic factors randomly assigned with a stipulated probability. The number of times the allocation could have been determined with certainty and the imbalances which might occur following randomisation using minimisation were examined. Overall treatment balance is relatively unaffected by reducing the probability of allocation to optimal treatment group (P) but within-variable balance can be affected by any P <1. This effect is magnified by increased numbers of prognostic variables, the number of categories within them and the prevalence of these categories within the study population. In general, for smaller trials, probability of treatment allocation to the treatment group with fewer numbers requires a larger value P to keep treatment and variable groups balanced. For larger trials probability of allocation values from P = 0.5 to P = 0.8 can be used while still maintaining balance. For one prognostic variable there is no significant benefit in terms of predictability in reducing the value of P. However, for more than one prognostic variable, significant reduction in levels of predictability can be achieved with the appropriate choice of P for the given trial design.
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.
Kang, Yeon-Koo; Song, Yoo Sung; Cho, Sukki; Jheon, Sanghoon; Lee, Won Woo; Kim, Kwhanmien; Kim, Sang Eun
2018-05-01
In the management of non-small cell lung cancer (NSCLC), the prognostic stratification of stage I tumors without indication of adjuvant therapy, remains to be elucidated in order to better select patients who can benefit from additional therapies. We aimed to stratify the prognosis of patients with stage I NSCLC adenocarcinoma using clinicopathologic factors and F-18 FDG PET. We retrospectively enrolled 128 patients with stage I NSCLC without any high-risk factors, who underwent curative surgical resection without adjuvant therapies. Preoperative clinical and postoperative pathologic factors were evaluated by medical record review. Standardized uptake value corrected with lean body mass (SUL max ) was measured on F-18 FDG PET. Among the factors, independent predictors for recurrence-free survival (RFS) were selected using univariate and stepwise multivariate survival analyses. A prognostic stratification model for RFS was designed using the selected factors. Tumors recurred in nineteen patients (14.8%). Among the investigated clinicopathologic and FDG PET factors, SUL max on PET and spread through air spaces (STAS) on pathologic review were determined to be independent prognostic factors for RFS. A prognostic model was designed using these two factors in the following manner: (1) Low-risk: SUL max ≤ 1.9 and no STAS, (2) intermediate-risk: neither low-risk nor high-risk, (3) high-risk: SUL max> 1.9 and observed STAS. This model exhibited significant predictive power for RFS. We showed that FDG uptake and STAS are significant prognostic markers in stage I NSCLC adenocarcinoma treated with surgical resection without adjuvant therapies. Copyright © 2018 Elsevier B.V. All rights reserved.
Forecasting municipal solid waste generation using prognostic tools and regression analysis.
Ghinea, Cristina; Drăgoi, Elena Niculina; Comăniţă, Elena-Diana; Gavrilescu, Marius; Câmpean, Teofil; Curteanu, Silvia; Gavrilescu, Maria
2016-11-01
For an adequate planning of waste management systems the accurate forecast of waste generation is an essential step, since various factors can affect waste trends. The application of predictive and prognosis models are useful tools, as reliable support for decision making processes. In this paper some indicators such as: number of residents, population age, urban life expectancy, total municipal solid waste were used as input variables in prognostic models in order to predict the amount of solid waste fractions. We applied Waste Prognostic Tool, regression analysis and time series analysis to forecast municipal solid waste generation and composition by considering the Iasi Romania case study. Regression equations were determined for six solid waste fractions (paper, plastic, metal, glass, biodegradable and other waste). Accuracy Measures were calculated and the results showed that S-curve trend model is the most suitable for municipal solid waste (MSW) prediction. Copyright © 2016 Elsevier Ltd. All rights reserved.
Kim, Seok Jin; Yoon, Dok Hyun; Jaccard, Arnaud; Chng, Wee Joo; Lim, Soon Thye; Hong, Huangming; Park, Yong; Chang, Kian Meng; Maeda, Yoshinobu; Ishida, Fumihiro; Shin, Dong-Yeop; Kim, Jin Seok; Jeong, Seong Hyun; Yang, Deok-Hwan; Jo, Jae-Cheol; Lee, Gyeong-Won; Choi, Chul Won; Lee, Won-Sik; Chen, Tsai-Yun; Kim, Kiyeun; Jung, Sin-Ho; Murayama, Tohru; Oki, Yasuhiro; Advani, Ranjana; d'Amore, Francesco; Schmitz, Norbert; Suh, Cheolwon; Suzuki, Ritsuro; Kwong, Yok Lam; Lin, Tong-Yu; Kim, Won Seog
2016-03-01
The clinical outcome of extranodal natural killer T-cell lymphoma (ENKTL) has improved substantially as a result of new treatment strategies with non-anthracycline-based chemotherapies and upfront use of concurrent chemoradiotherapy or radiotherapy. A new prognostic model based on the outcomes obtained with these contemporary treatments was warranted. We did a retrospective study of patients with newly diagnosed ENKTL without any previous treatment history for the disease who were given non-anthracycline-based chemotherapies with or without upfront concurrent chemoradiotherapy or radiotherapy with curative intent. A prognostic model to predict overall survival and progression-free survival on the basis of pretreatment clinical and laboratory characteristics was developed by filling a multivariable model on the basis of the dataset with complete data for the selected risk factors for an unbiased prediction model. The final model was applied to the patients who had complete data for the selected risk factors. We did a validation analysis of the prognostic model in an independent cohort. We did multivariate analyses of 527 patients who were included from 38 hospitals in 11 countries in the training cohort. Analyses showed that age greater than 60 years, stage III or IV disease, distant lymph-node involvement, and non-nasal type disease were significantly associated with overall survival and progression-free survival. We used these data as the basis for the prognostic index of natural killer lymphoma (PINK), in which patients are stratified into low-risk (no risk factors), intermediate-risk (one risk factor), or high-risk (two or more risk factors) groups, which were associated with 3-year overall survival of 81% (95% CI 75-86), 62% (55-70), and 25% (20-34), respectively. In the 328 patients with data for Epstein-Barr virus DNA, a detectable viral DNA titre was an independent prognostic factor for overall survival. When these data were added to PINK as the basis for another prognostic index (PINK-E)-which had similar low-risk (zero or one risk factor), intermediate-risk (two risk factors), and high-risk (three or more risk factors) categories-significant associations with overall survival were noted (81% [95% CI 75-87%], 55% (44-66), and 28% (18-40%), respectively). These results were validated and confirmed in an independent cohort, although the PINK-E model was only significantly associated with the high-risk group compared with the low-risk group. PINK and PINK-E are new prognostic models that can be used to develop risk-adapted treatment approaches for patients with ENKTL being treated in the contemporary era of non-anthracycline-based therapy. Samsung Biomedical Research Institute. Copyright © 2016 Elsevier Ltd. All rights reserved.
Henrie, Adam M; Wittstrom, Kristina; Delu, Adam; Deming, Paulina
2015-09-01
The objective of this study was to examine indicators of liver function and inflammation for prognostic value in predicting outcomes to yttrium-90 radioembolization (RE). In a retrospective analysis, markers of liver function and inflammation, biomarkers required to stage liver function and inflammation, and data regarding survival, tumor response, and progression after RE were recorded. Univariate regression models were used to investigate the prognostic value of liver biomarkers in predicting outcome to RE as measured by survival, tumor progression, and radiographic and biochemical tumor response. Markers from all malignancy types were analyzed together. A subgroup analysis was performed on markers from patients with metastatic colorectal cancer. A total of 31 patients received RE from 2004 to 2014. Median survival after RE for all malignancies combined was 13.6 months (95% CI: 6.7-17.6 months). Results from an exploratory analysis of patient data suggest that liver biomarkers, including albumin concentrations, international normalized ratio, bilirubin concentrations, and the model for end-stage liver disease score, possess prognostic value in predicting outcomes to RE.
The role of anti-cyclic citrullinated peptide antibodies in predicting rheumatoid arthritis.
Rexhepi, Sylejman; Rexhepi, Mjellma; Sahatçiu-Meka, Vjollca; Tafaj, Argjend; Izairi, Remzi; Rexhepi, Blerta
2011-01-01
The study presents the results of predicting role of anti-cyclic citrullinated peptide antibodies in rheumatoid arthritis, compared to rheumatoid factor. 32 patients with rheumatoid arthritis were identified from a retrospective chart review. The results of our study show that presence of the rheumatoid factor has less diagnostic and prognostic significance than the anti-cyclic citrullinated peptide, and suggests its superiority in predicting an erosive disease course.
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.
2014-01-01
Introduction Using genome-wide expression profiles of a prospective training cohort of breast cancer patients, ClinicoMolecular Triad Classification (CMTC) was recently developed to classify breast cancers into three clinically relevant groups to aid treatment decisions. CMTC was found to be both prognostic and predictive in a large external breast cancer cohort in that study. This study serves to validate the reproducibility of CMTC and its prognostic value using independent patient cohorts. Methods An independent internal cohort (n = 284) and a new external cohort (n = 2,181) were used to validate the association of CMTC between clinicopathological factors, 12 known gene signatures, two molecular subtype classifiers, and 19 oncogenic signalling pathway activities, and to reproduce the abilities of CMTC to predict clinical outcomes of breast cancer. In addition, we also updated the outcome data of the original training cohort (n = 147). Results The original training cohort reached a statistically significant difference (p < 0.05) in disease-free survivals between the three CMTC groups after an additional two years of follow-up (median = 55 months). The prognostic value of the triad classification was reproduced in the second independent internal cohort and the new external validation cohort. CMTC achieved even higher prognostic significance when all available patients were analyzed (n = 4,851). Oncogenic pathways Myc, E2F1, Ras and β-catenin were again implicated in the high-risk groups. Conclusions Both prospective internal cohorts and the independent external cohorts reproduced the triad classification of CMTC and its prognostic significance. CMTC is an independent prognostic predictor, and it outperformed 12 other known prognostic gene signatures, molecular subtype classifications, and all other standard prognostic clinicopathological factors. Our results support further development of CMTC portfolio into a guide for personalized breast cancer treatments. PMID:24996446
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
Lo, Benjamin W Y; Fukuda, Hitoshi; Angle, Mark; Teitelbaum, Jeanne; Macdonald, R Loch; Farrokhyar, Forough; Thabane, Lehana; Levine, Mitchell A H
2016-01-01
Classification and regression tree analysis involves the creation of a decision tree by recursive partitioning of a dataset into more homogeneous subgroups. Thus far, there is scarce literature on using this technique to create clinical prediction tools for aneurysmal subarachnoid hemorrhage (SAH). The classification and regression tree analysis technique was applied to the multicenter Tirilazad database (3551 patients) in order to create the decision-making algorithm. In order to elucidate prognostic subgroups in aneurysmal SAH, neurologic, systemic, and demographic factors were taken into account. The dependent variable used for analysis was the dichotomized Glasgow Outcome Score at 3 months. Classification and regression tree analysis revealed seven prognostic subgroups. Neurological grade, occurrence of post-admission stroke, occurrence of post-admission fever, and age represented the explanatory nodes of this decision tree. Split sample validation revealed classification accuracy of 79% for the training dataset and 77% for the testing dataset. In addition, the occurrence of fever at 1-week post-aneurysmal SAH is associated with increased odds of post-admission stroke (odds ratio: 1.83, 95% confidence interval: 1.56-2.45, P < 0.01). A clinically useful classification tree was generated, which serves as a prediction tool to guide bedside prognostication and clinical treatment decision making. This prognostic decision-making algorithm also shed light on the complex interactions between a number of risk factors in determining outcome after aneurysmal SAH.
Chen, Zhiqiang; Pu, Liyong; Gao, Wen; Zhang, Long; Han, Guoyong; Zhu, Qin; Li, Xiangcheng; Wu, Jindao; Wang, Xuehao
2017-04-25
Although the prognostic value of marital status has been implicated in many cancers, its prognostic impact on cholangiocarcinoma has not yet been determined. The aim of this study was to examine the association between marital status and cholangiocarcinoma survival. We included 8,776 extrahepatic cholangiocarcinoma cases and 1,352 intrahepatic cholangiocarcinoma cases between 1973 and 2013 from the Surveillance, Epidemiology, and End Results database. We found widowed patients were more likely to be female, aged more than 70, and from low income areas. Multivariate analysis indicated that marital status was an independent prognostic factor for extrahepatic cholangiocarcinoma patients. Subgroup analysis suggested the widowed status independently predicted poor survival at regional stage and in older patients with intrahepatic cholangiocarcinoma. To conclude, marital status is a valuable prognostic factor in cholangiocarcinoma, and widowed patients are at greater risk of death than others.
Michikawa, C; Izumo, T; Sumino, J; Morita, T; Ohyama, Y; Michi, Y; Uzawa, N
2018-07-01
Extracapsular spread (ECS) of metastatic lymph nodes from oral carcinoma is the most significant prognostic predictor of a poor treatment outcome. However, only a few reports on prognostic factors in ECS-positive cases have been investigated. To address this problem, a detailed examination of ECS pathology was conducted to determine the prognostic factors of oral squamous cell carcinoma (OSCC) with ECS of metastatic lymph nodes. This study involved 63 OSCC patients with at least one pathologically metastatic node with ECS. Among the 229 metastatic lymph nodes, 149 exhibited ECS. Univariate analysis revealed that a poor outcome and recurrence were significantly associated with the number of ECS-positive nodes, density of ECS, and the minor axis of the smallest ECS-positive node. However, multivariate analysis identified only small size of ECS-positive nodes as a significant and independent factor predicting recurrence and a poor outcome. Thus, small size of ECS-positive nodes is the most important prognostic indicator for OSCC with ECS in metastatic lymph nodes. The classification of ECS status using the minor axis of ECS-positive nodes may be useful for further prediction of a poorer prognosis in OSCC cases. Standardization of ECS diagnosis and multicenter prospective studies will be required to confirm and refine these findings. Copyright © 2017 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
Liu, Mu-Tai; Chen, Mu-Kuan; Huang, Chia-Chun; Huang, Chao-Yuan
2015-02-01
The aim of the study was to evaluate the prognostic significance of molecular biomarkers which could provide information for more accurate prognostication and development of novel therapeutic strategies for nasopharyngeal carcinoma (NPC). NPC is a unique malignant epithelial carcinoma of head and neck region, with an intimate association with the Epstein-Barr virus (EBV). Currently, the prediction of NPC prognosis is mainly based on the clinical TNM staging; however, NPC patients with the same clinical stage often present different clinical outcomes, suggesting that the TNM stage is insufficient to precisely predict the prognosis of this disease. In this review, we give an overview of the prognostic value of molecular markers in NPC and discuss potential strategies of targeted therapies for treatment of NPC. Molecular biomarkers, which play roles in abnormal proliferation signaling pathways (such as Wnt/β-catenin pathway), intracellular mitogenic signal aberration (such as hypoxia-inducible factor (HIF)-1α), receptor-mediated aberrations (such as vascular endothelial growth factor (VEGF)), tumor suppressors (such as p16 and p27 activity), cell cycle aberrations (such as cyclin D1 and cyclin E), cell adhesion aberrations (such as E-cadherin), apoptosis dysregualtion (such as survivin) and centromere aberration (centromere protein H), are prognostic markers for NPC. Plasma EBV DNA concentrations and EBV-encoded latent membrane proteins are also prognostic markers for NPC. Implication of molecular targeted therapies in NPC was discussed. Such therapies could have potential in combination with different cytotoxic agents to combat and eradicate tumor cells. In order to further improve overall survival for patients with loco-regionally advanced NPC, the development of innovative strategies, including prognostic molecular markers and molecular targeted agents is needed.
Cotte, E; Peyrat, P; Piaton, E; Chapuis, F; Rivoire, M; Glehen, O; Arvieux, C; Mabrut, J-Y; Chipponi, J; Gilly, F-N
2013-07-01
In digestive cancers, the prognostic significance of intraperitoneal free cancer cells remains unclear (IPCC). The main objective of this study was to assess the prognostic significance of IPCC in colorectal and gastric adenocarcinoma. The secondary objectives were to evaluate the predictive significance of IPCC for the development of peritoneal carcinomatosis (PC) and to evaluate the prevalence of synchronous PC and IPCC. This was a prospective multicentre study. All patients undergoing surgery for a digestive tract cancer had peritoneal cytology taken. Patients with gastric and colorectal cancer with no residual tumour after surgery and no evidence of PC were followed-up for 2 years. The primary end point was overall survival. Between 2002 and 2007, 1364 patients were enrolled and 956 were followed-up over 2 years. Prevalence of IPCC was 5.7% in colon cancer, 0.6% in rectal cancer and 19.5% in gastric cancer. The overall 2-year survival rate for patients with IPCC was 34.7% versus 86.8% for patients with negative cytology (p<0.0001). By multivariate analysis, IPCC was not an independent prognostic factor. No relationship between cytology and recurrence was found. The presence of IPCC was not an independent prognostic and didn't add any additional prognostic information to the usual prognostic factors related to the tumour (pTNM and differentiation). Moreover the presence of IPCC detected with this method didn't appear to predict development of PC. Peritoneal cytology using conventional staining doesn't seem to be a useful tool for the staging of colorectal and gastric cancers. Copyright © 2013 Elsevier Ltd. All rights reserved.
A new prognostic score for AIDS-related lymphomas in the rituximab-era
Barta, Stefan K.; Xue, Xiaonan; Wang, Dan; Lee, Jeannette Y.; Kaplan, Lawrence D.; Ribera, Josep-Maria; Oriol, Albert; Spina, Michele; Tirelli, Umberto; Boue, Francois; Wilson, Wyndham H.; Wyen, Christoph; Dunleavy, Kieron; Noy, Ariela; Sparano, Joseph A.
2014-01-01
While the International Prognostic Index is commonly used to predict outcomes in immunocompetent patients with aggressive B-cell non-Hodgkin lymphomas, HIV-infection is an important competing risk for death in patients with AIDS-related lymphomas. We investigated whether a newly created prognostic score (AIDS-related lymphoma International Prognostic Index) could better assess risk of death in patients with AIDS-related lymphomas. We randomly divided a dataset of 487 patients newly diagnosed with AIDS-related lymphomas and treated with rituximab-containing chemoimmunotherapy into a training (n=244) and validation (n=243) set. We examined the association of HIV-related and other known risk factors with overall survival in both sets independently. We defined a new score (AIDS-related lymphoma International Prognostic Index) by assigning weights to each significant predictor [age-adjusted International Prognostic Index, extranodal sites, HIV-score (composed of CD4 count, viral load, and prior history of AIDS)] with three risk categories similar to the age-adjusted International Prognostic Index (low, intermediate and high risk). We compared the prognostic value for overall survival between AIDS-related lymphoma International Prognostic Index and age-adjusted International Prognostic Index in the validation set and found that the AIDS-related lymphoma International Prognostic Index performed significantly better in predicting risk of death than the age-adjusted International Prognostic Index (P=0.004) and better discriminated risk of death between each risk category (P=0.015 vs. P=0.13). Twenty-eight percent of patients were defined as low risk by the ARL-IPI and had an estimated 5-year overall survival (OS) of 78% (52% intermediate risk, 5-year OS 60%; 20% high risk, 5-year OS 50%). PMID:25150257
Prognostic factors, pathophysiology and novel biomarkers in Crimean-Congo hemorrhagic fever.
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.
Mortality-related Factors in Patients with Malignant Obstructive Jaundice.
Kurniawan, Juferdy; Hasan, Irsan; Gani, Rino Alvani; Simadibrata, Marcellus
2016-10-01
to obtain survival rate and mortality-related factors of malignant obstructive jaundice patients. all medical records of obstructive jaundice inpatient at Cipto Mangunkusumo Hospital, Jakarta from January 2010 to December 2013 were reviewed retrospectively. The following factors were analyzed in terms of mortality: age, gender, sepsis, hypoalbumin, serum bilirubin level, serum CA 19-9 level, billiary drainage, non-ampulla Vateri carcinoma, and comorbid factors. total 181 out of 402 patients were enrolled in this study with male proportion was 58.6%, and patients aged 50 years or above was 57.5%. Multivariate analysis showed that only sepsis, unsuccessful or no prior biliary drainage and Charlson comorbid score ≥4 were independent predictors of mortality. Patients with significant prognostic factors had median survival 14 days compared with overall median survival 26 days. Score ≥2 identified as the highest prognostic score threshold with sensitivity 68%, specificity 75%, and AUC on ROC curve 0.769. sepsis, unsuccessful or no prior bilirary drainage, and Charlson comorbid score ≥4 are factors significantly associated with shortened survival in malignant obstructive jaundice patients. Prognostic score ≥2 was determined to classify patients into high risk mortality group. Mortality of patients with those significant prognostic factors can be predicted in 76.9%.
Zhang, Lixiang; Su, Yezhou; Chen, Zhangming; Wei, Zhijian; Han, Wenxiu; Xu, Aman
2017-07-01
Immune and nutritional status of patients have been reported to predict postoperative complications, recurrence, and prognosis of patients with cancer. Therefore, this retrospective study aimed to explore the prognostic value of preoperative inflammation-based prognostic scores [neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR)] and nutritional status [prognostic nutritional index (PNI), body mass index (BMI), hemoglobin, albumin, and prealbumin] for overall survival (OS) in adenocarcinoma of esophagogastric junction (AEG) patients. A total of 355 patients diagnosed with Siewert type II/III AEG and underwent surgery between October 2010 and December 2011 were followed up until October 2016. Receiver operating characteristic (ROC) curve analysis was used to determine the cutoff values of NLR, PLR, and PNI. Kaplan-Meier curves and Cox regression analyses were used to calculate the OS characteristics. The ideal cutoff values for predicting OS were 3.5 for NLR, 171 for PLR, and 51.3 for PNI according to the ROC curve. The patients with hemoglobin <120 g/L (P = .001), prealbumin <180 mg/L (P = .000), PNI <51.3 (P = .010), NLR >3.5 (P = .000), PLR >171 (P = .006), and low BMI group (P = .000) had shorter OS. And multivariate survival analysis using the Cox proportional hazards model showed that the tumor-node-metastasis stage, BMI, NLR, and prealbumin levels were independent risk factors for the OS. Our study demonstrated that preoperative prealbumin, BMI, and NLR were independent prognostic factors of AEG patients.
Prognostic model for survival in patients with early stage cervical cancer.
Biewenga, Petra; van der Velden, Jacobus; Mol, Ben Willem J; Stalpers, Lukas J A; Schilthuis, Marten S; van der Steeg, Jan Willem; Burger, Matthé P M; Buist, Marrije R
2011-02-15
In the management of early stage cervical cancer, knowledge about the prognosis is critical. Although many factors have an impact on survival, their relative importance remains controversial. This study aims to develop a prognostic model for survival in early stage cervical cancer patients and to reconsider grounds for adjuvant treatment. A multivariate Cox regression model was used to identify the prognostic weight of clinical and histological factors for disease-specific survival (DSS) in 710 consecutive patients who had surgery for early stage cervical cancer (FIGO [International Federation of Gynecology and Obstetrics] stage IA2-IIA). Prognostic scores were derived by converting the regression coefficients for each prognostic marker and used in a score chart. The discriminative capacity was expressed as the area under the curve (AUC) of the receiver operating characteristic. The 5-year DSS was 92%. Tumor diameter, histological type, lymph node metastasis, depth of stromal invasion, lymph vascular space invasion, and parametrial extension were independently associated with DSS and were included in a Cox regression model. This prognostic model, corrected for the 9% overfit shown by internal validation, showed a fair discriminative capacity (AUC, 0.73). The derived score chart predicting 5-year DSS showed a good discriminative capacity (AUC, 0.85). In patients with early stage cervical cancer, DSS can be predicted with a statistical model. Models, such as that presented here, should be used in clinical trials on the effects of adjuvant treatments in high-risk early cervical cancer patients, both to stratify and to include patients. Copyright © 2010 American Cancer Society.
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.
Choudhury, Ananya; West, Catharine M; Porta, Nuria; Hall, Emma; Denley, Helen; Hendron, Carey; Lewis, Rebecca; Hussain, Syed A; Huddart, Robert; James, Nicholas
2017-01-01
Background: Severe chronic hypoxia is associated with tumour necrosis. In patients with muscle invasive bladder cancer (MIBC), necrosis is prognostic for survival following surgery or radiotherapy and predicts benefit from hypoxia modification of radiotherapy. Adding mitomycin C (MMC) and 5-fluorouracil (5-FU) chemotherapy to radiotherapy improved locoregional control (LRC) compared to radiotherapy alone in the BC2001 trial. We hypothesised that tumour necrosis would not predict benefit for the addition of MMC and 5-FU to radiotherapy, but would be prognostic. Methods: Diagnostic tumour samples were available from 230 BC2001 patients. Tumour necrosis was scored on whole-tissue sections as absent or present, and its predictive and prognostic significance explored using Cox proportional hazards models. Survival estimates were obtained by Kaplan–Meier methods. Results: Tumour necrosis was present in 88/230 (38%) samples. Two-year LRC estimates were 71% (95% CI 61–79%) for the MMC/5-FU chemoradiotherapy group and 49% (95% CI 38–59%) for the radiotherapy alone group. When analysed by tumour necrosis status, the adjusted hazard ratios (HR) for MMC/5-FU vs. no chemotherapy were 0.46 (95% CI: 0.12–0.99; P=0.05, necrosis present) and 0.55 (95% CI: 0.31–0.98; P=0.04, necrosis absent). Multivariable analysis of prognosis for LRC by the presence vs. absence of necrosis yielded a HR=0.89 (95% CI 0.55–1.44, P=0.65). There was no significant association for necrosis as a predictive or prognostic factor with respect to overall survival. Conclusions: Tumour necrosis was neither predictive nor prognostic, and therefore MMC/5-FU is an appropriate radiotherapy-sensitising treatment in MIBC independent of necrosis status. PMID:28125821
Viale, Giuseppe; Giobbie-Hurder, Anita; Regan, Meredith M; Coates, Alan S; Mastropasqua, Mauro G; Dell'Orto, Patrizia; Maiorano, Eugenio; MacGrogan, Gaëtan; Braye, Stephen G; Ohlschlegel, Christian; Neven, Patrick; Orosz, Zsolt; Olszewski, Wojciech P; Knox, Fiona; Thürlimann, Beat; Price, Karen N; Castiglione-Gertsch, Monica; Gelber, Richard D; Gusterson, Barry A; Goldhirsch, Aron
2008-12-01
To evaluate the prognostic and predictive value of Ki-67 labeling index (LI) in a trial comparing letrozole (Let) with tamoxifen (Tam) as adjuvant therapy in postmenopausal women with early breast cancer. Breast International Group (BIG) trial 1-98 randomly assigned 8,010 patients to four treatment arms comparing Let and Tam with sequences of each agent. Of 4,922 patients randomly assigned to receive 5 years of monotherapy with either agent, 2,685 had primary tumor material available for central pathology assessment of Ki-67 LI by immunohistochemistry and had tumors confirmed to express estrogen receptors after central review. The prognostic and predictive value of centrally measured Ki-67 LI on disease-free survival (DFS) were assessed among these patients using proportional hazards modeling, with Ki-67 LI values dichotomized at the median value of 11%. Higher values of Ki-67 LI were associated with adverse prognostic factors and with worse DFS (hazard ratio [HR; high:low] = 1.8; 95% CI, 1.4 to 2.3). The magnitude of the treatment benefit for Let versus Tam was greater among patients with high tumor Ki-67 LI (HR [Let:Tam] = 0.53; 95% CI, 0.39 to 0.72) than among patients with low tumor Ki-67 LI (HR [Let:Tam] = 0.81; 95% CI, 0.57 to 1.15; interaction P = .09). Ki-67 LI is confirmed as a prognostic factor in this study. High Ki-67 LI levels may identify a patient group that particularly benefits from initial Let adjuvant therapy.
Ning, Zhong-Hua; Zhao, Wei; Li, Xiao-Dong; Chen, Lu-Jun; Xu, Bin; Gu, Wen-Dong; Shao, Ying-Jie; Xu, Yun; Huang, Jin; Pei, Hong-Lei; Jiang, Jing-Ting
2015-01-01
Prognosis of locally advanced esophageal squamous cell carcinoma (ESCC) remains dismal even after curative resection and adjuvant radiotherapy. New biomarkers for predicting prognosis and treatment outcomes are needed for improved treatment stratification of patients with locally advanced ESCC. The prognostic and treatment predictive significance of perineural invasion (PNI) in the locally advanced ESCC remains unclear. This study aimed to examine the effect of PNI on the outcomes of locally advanced ESCC patients after curative resection with or without postoperative radiotherapy (PORT). We retrospectively reviewed 262 consecutive locally advanced ESCC patients who underwent curative resection. Tumors sections were re-evaluated for PNI by an independent pathologist blinded to the patients' outcomes. Overall survival (OS) and disease-free survival (DFS) were determined using the Kaplan-Meier method; univariate log-rank test and multivariate Cox proportional hazard model were used to evaluate the prognostic value of PNI. Finally, 243 patients were analyzed and enrolled into this study, of which 132 received PORT. PNI was identified in 22.2% (54/243) of the pathologic sections. The 5-year DFS was favorable for PNI-negative patients versus PNI-positive patients (21.3% vs. 36.7%, respectively; P = 0.005). The 5-year OS was 40.3% for PNI-negative patients versus 21.7% for PNI-positive patients (P < 0.001). On multivariate analysis, PNI was an independent prognostic factor. In a subset analysis for patients received PORT, PNI was evaluated as a prognostic predictor as well (P < 0.05). In contrast to patients without PORT, PORT couldn't improve the disease recurrence and survival in locally advanced ESCC patients with PNI-positive (P > 0.05). PNI could serve as an independent prognostic factor and prognosticate treatment outcomes in locally advanced ESCC patients. The PNI status should be considered when stratifying high-risk locally advanced ESCC patients for adjuvant radiotherapy. Future prospective study is warranted to confirm our results.
Malka, D; Boige, V; Jacques, N; Vimond, N; Adenis, A; Boucher, E; Pierga, J Y; Conroy, T; Chauffert, B; François, E; Guichard, P; Galais, M P; Cvitkovic, F; Ducreux, M; Farace, F
2012-04-01
We investigated whether circulating endothelial cells (CECs) predict clinical outcome of first-line chemotherapy and bevacizumab in metastatic colorectal cancer (mCRC) patients. In a substudy of the randomized phase II FNCLCC ACCORD 13/0503 trial, CECs (CD45- CD31+ CD146+ 7-amino-actinomycin- cells) were enumerated in 99 patients by four-color flow cytometry at baseline and after one cycle of treatment. We correlated CEC levels with objective response rate (ORR), 6-month progression-free survival (PFS) rate (primary end point of the trial), PFS, and overall survival (OS). Multivariate analyses of potential prognostic factors, including CEC counts and Köhne score, were carried out. By multivariate analysis, high baseline CEC levels were the only independent prognostic factor for 6-month PFS rate (P < 0.01) and were independently associated with worse PFS (P = 0.02). High CEC levels after one cycle were the only independent prognostic factor for ORR (P = 0.03). High CEC levels at both time points independently predicted worse ORR (P = 0.025), 6-month PFS rate (P = 0.007), and PFS (P = 0.02). Köhne score was the only variable associated with OS. CEC levels at baseline and after one treatment cycle may independently predict ORR and PFS in mCRC patients starting first-line bevacizumab and chemotherapy.
Lee, Jee Youn; Kim, Hyoung-Il; Kim, You-Na; Hong, Jung Hwa; Alshomimi, Saeed; An, Ji Yeong; Cheong, Jae-Ho; Hyung, Woo Jin; Noh, Sung Hoon; Kim, Choong-Bai
2016-05-01
To evaluate the predictive and prognostic significance of the prognostic nutritional index (PNI) in a large cohort of gastric cancer patients who underwent gastrectomy.Assessing a patient's immune and nutritional status, PNI has been reported as a predictive marker for surgical outcomes in various types of cancer.We retrospectively reviewed data from a prospectively maintained database of 7781 gastric cancer patients who underwent gastrectomy from January 2001 to December 2010 at a single center. From this data, we analyzed clinicopathologic characteristics, PNI, and short- and long-term surgical outcomes for each patient. We used the PNI value for the 10th percentile (46.70) of the study cohort as a cut-off for dividing patients into low and high PNI groups.Regarding short-term outcomes, multivariate analysis showed a low PNI (odds ratio [OR] = 1.505, 95% CI = 1.212-1.869, P <0.001), old age, male sex, high body mass index, medical comorbidity, total gastrectomy, and combined resection to be independent predictors of postoperative complications. Among these, only low PNI (OR = 4.279, 95% CI = 1.760-10.404, P = 0.001) and medical comorbidity were independent predictors of postoperative mortality. For long-term outcomes, low PNI was a poor prognostic factor for overall survival, but not recurrence (overall survival: hazard ratio [HR] = 1.383, 95% CI = 1.221-1.568, P < 0.001; recurrence-free survival: HR = 1.142, 95% CI = 0.985-1.325, P = 0.078).PNI can be used to predict patients at increased risk of postoperative morbidity and mortality. Although PNI was an independent prognostic factor for overall survival, the index was not associated with cancer recurrence.
Using prognostic models in CLL to personalize approach to clinical care: Are we there yet?
Mina, Alain; Sandoval Sus, Jose; Sleiman, Elsa; Pinilla-Ibarz, Javier; Awan, Farrukh T; Kharfan-Dabaja, Mohamed A
2018-03-01
Four decades ago, two staging systems were developed to help stratify CLL into different prognostic categories. These systems, the Rai and the Binet staging, depended entirely on abnormal exam findings and evidence of anemia and thrombocytopenia. Better understanding of biologic, genetic, and molecular characteristics of CLL have contributed to better appreciating its clinical heterogeneity. New prognostic models, the GCLLSG prognostic index and the CLL-IPI, emerged. They incorporate biologic and genetic information related to CLL and are capable of predicting survival outcomes and cases anticipated to need therapy earlier in the disease course. Accordingly, these newer models are helping develop better informed surveillance strategies and ultimately tailor treatment intensity according to presence (or lack thereof) of certain prognostic markers. This represents a step towards personalizing care of CLL patients. We anticipate that as more prognostic factors continue to be identified, the GCLLSG prognostic index and CLL-IPI models will undergo further revisions. Copyright © 2017 Elsevier Ltd. All rights reserved.
NASA Astrophysics Data System (ADS)
Chaudhury, Baishali; Zhou, Mu; Farhidzadeh, Hamidreza; Goldgof, Dmitry B.; Hall, Lawrence O.; Gatenby, Robert A.; Gillies, Robert J.; Weinfurtner, Robert J.; Drukteinis, Jennifer S.
2016-03-01
The use of Ki67% expression, a cell proliferation marker, as a predictive and prognostic factor has been widely studied in the literature. Yet its usefulness is limited due to inconsistent cut off scores for Ki67% expression, subjective differences in its assessment in various studies, and spatial variation in expression, which makes it difficult to reproduce as a reliable independent prognostic factor. Previous studies have shown that there are significant spatial variations in Ki67% expression, which may limit its clinical prognostic utility after core biopsy. These variations are most evident when examining the periphery of the tumor vs. the core. To date, prediction of Ki67% expression from quantitative image analysis of DCE-MRI is very limited. This work presents a novel computer aided diagnosis framework to use textural kinetics to (i) predict the ratio of periphery Ki67% expression to core Ki67% expression, and (ii) predict Ki67% expression from individual tumor habitats. The pilot cohort consists of T1 weighted fat saturated DCE-MR images from 17 patients. Support vector regression with a radial basis function was used for predicting the Ki67% expression and ratios. The initial results show that texture features from individual tumor habitats are more predictive of the Ki67% expression ratio and spatial Ki67% expression than features from the whole tumor. The Ki67% expression ratio could be predicted with a root mean square error (RMSE) of 1.67%. Quantitative image analysis of DCE-MRI using textural kinetic habitats, has the potential to be used as a non-invasive method for predicting Ki67 percentage and ratio, thus more accurately reporting high KI-67 expression for patient prognosis.
van Middelkoop, Marienke; van Rijn, Rogier M; Verhaar, Jan A N; Koes, Bart W; Bierma-Zeinstra, Sita M A
2012-01-01
What are prognostic factors for incomplete recovery, instability, re-sprains and pain intensity 12 months after patients consult primary care practitioners for acute ankle sprains? Observational study. One hundred and two patients who consulted their general practitioner or an emergency department for an acute ankle sprain were included in the study. Possible prognostic factors were assessed at baseline and at 3 months follow-up. Outcome measures assessed at 12 months follow-up were self-reported recovery, instability, re-sprains and pain intensity. At 3 months follow-up, 65% of the participants reported instability and 24% reported one or more re-sprains. At 12 months follow-up, 55% still reported instability and more than 50% regarded themselves not completely recovered. None of the factors measured at baseline could predict the outcome at 12 months follow-up. Additionally, prognostic factors from the physical examination of the non-recovered participants at 3 months could not be identified. However, among the non-recovered participants at 3 months follow-up, re-sprains and self-reported pain at rest at 3 months were related to incomplete recovery at 12 months. A physical examination at 3 months follow-up for the non-recovered ankle sprain patient seems to have no additional value for predicting outcome at 12 months. However, for the non-recovered patients at 3 months follow-up, self-reported pain at rest and re-sprains during the first 3 months of follow-up seem to have a prognostic value for recovery at 12 months. Copyright © 2012 Australian Physiotherapy Association. Published by .. All rights reserved.
Kwon, Jong-Bum; Park, Khun; Kim, Young-Du; Seo, Jong-Hee; Moon, Seok-Whan; Cho, Deog-Gon; Kim, Yong-Whan; Kim, Dong-Goo; Yoon, Seung-Kew; Lim, Hyeon-Woo
2008-01-01
AIM: To review the surgical outcomes in terms of the surgical indications and relevant prognostic factors. METHODS: Sixteen patients underwent therapeutic lung surgery between March 1999 and May 2006. The observation period was terminated on May 31, 2007. The surgical outcomes and the clinicopathological factors were compared. RESULTS: There was no mortality or major morbidity encountered in this study. The mean follow-up period after metastasectomy was 26.7 ± 28.2 (range: 1-99 mo), and the median survival time was 20 mo. The 1- and 5-year survival rates were 56% and 26%, respectively. At the end of the follow-up, 1 patient died from hepatic failure without recurrence, 6 died from hepatic failure with a recurrent hepatocellular carcinoma (HCC), and 4 died from recurrent HCC with cachexia. Among several clinical factors, Kaplan-Meier analysis revealed that liver transplantation as a treatment for the primary lesion, grade of cell differentiation, and negative evidence HBV infection were independent predictive factors. On Cox’s proportional hazard model, there were no significant factors affecting survival after pulmonary metastasectomy in patients with HCC. CONCLUSION: A metastasectomy should be performed before other treatments in selected patients. Although not significant, patients with liver transplantation of a primary HCC survived longer. Liver transplantation might be the most beneficial modality that can offer patients better survival. A multi-institutional and collaborative study would be needed for identifying clinical prognostic factors predicting survival in patients with HCC and lung metastasis. PMID:18837090
Yuan, Shu-Qiang; Nie, Run-Cong; Chen, Yong-Ming; Qiu, Hai-Bo; Li, Xiao-Ping; Chen, Xiao-Jiang; Xu, Li-Pu; Yang, Li-Fang; Sun, Xiao-Wei; Li, Yuan-Fang; Zhou, Zhi-Wei; Chen, Shi; Chen, Ying-Bo
2018-04-01
The Glasgow Prognostic Score (GPS) has been shown to be associated with survival rates in patients with advanced cancer. The present study aimed to compare the GPS with the Eastern Cooperative Oncology Group Performance Status (ECOG PS) in patients with gastric cancer with peritoneal seeding. For the investigation, a total of 384 gastric patients with peritoneal metastasis were retrospectively analyzed. Patients with elevated C-reactive protein (CRP; >10 mg/l) and hypoalbuminemia (<35 mg/l) were assigned a score of 2. Patients were assigned a score of 1 if presenting with only one of these abnormalities, and a score of 0 if neither of these abnormalities were present. The clinicopathologic characteristics and clinical outcomes of patients with peritoneal seeding were analyzed. The results showed that the median overall survival (OS) of patients in the GPS 0 group was longer, compared with that in the GPS 1 and GPS 2 groups (15.50, vs. 10.07 and 7.97 months, respectively; P<0.001). No significant difference was found between the median OS of patients with a good performance status (ECOG <2) and those with a poor (ECOG ≥2) performance status (13.67, vs. 11.80 months; P=0.076). In the subgroup analysis, the median OS in the GPS 0 group was significantly longer, compared with that in the GPS 1 and GPS 2 groups, for the patients receiving palliative chemotherapy and patients without palliative chemotherapy. Multivariate survival analysis demonstrated that CA19-9, palliative gastrectomy, first-line chemotherapy and GPS were the prognostic factors predicting OS. In conclusion, the GPS was superior to the subjective assessment of ECOG PS as a prognostic factor in predicting the outcome of gastric cancer with peritoneal seeding.
Adelian, R; Jamali, J; Zare, N; Ayatollahi, S M T; Pooladfar, G R; Roustaei, N
2015-01-01
Identification of the prognostic factors for survival in patients with liver transplantation is challengeable. Various methods of survival analysis have provided different, sometimes contradictory, results from the same data. To compare Cox's regression model with parametric models for determining the independent factors for predicting adults' and pediatrics' survival after liver transplantation. This study was conducted on 183 pediatric patients and 346 adults underwent liver transplantation in Namazi Hospital, Shiraz, southern Iran. The study population included all patients undergoing liver transplantation from 2000 to 2012. The prognostic factors sex, age, Child class, initial diagnosis of the liver disease, PELD/MELD score, and pre-operative laboratory markers were selected for survival analysis. Among 529 patients, 346 (64.5%) were adult and 183 (34.6%) were pediatric cases. Overall, the lognormal distribution was the best-fitting model for adult and pediatric patients. Age in adults (HR=1.16, p<0.05) and weight (HR=2.68, p<0.01) and Child class B (HR=2.12, p<0.05) in pediatric patients were the most important factors for prediction of survival after liver transplantation. Adult patients younger than the mean age and pediatric patients weighing above the mean and Child class A (compared to those with classes B or C) had better survival. Parametric regression model is a good alternative for the Cox's regression model.
Nakagawa, Akio; Nakamura, Tetsu; Oshikiri, Taro; Hasegawa, Hiroshi; Yamamoto, Masashi; Kanaji, Shingo; Matsuda, Yoshiko; Yamashita, Kimihiro; Matsuda, Takeru; Sumi, Yasuo; Suzuki, Satoshi; Kakeji, Yoshihiro
2017-12-01
The surgical Apgar score (SAS) quantifies three intraoperative factors and predicts postoperative complications, but few reports describe its usefulness in esophagectomy, and no studies to date show its correlation with long-term prognosis after esophagectomy. This study investigated 400 cases in which esophagectomy was performed on esophageal malignant tumors at the authors' hospital from January 2007 to January 2017. In this study, SAS was defined as the sum of the scores of three parameters, namely, estimated blood loss, lowest mean arterial pressure, and lowest heart rate, with values extracted from medical records. Postoperative complications classified as Clavien-Dindo grade 3 or higher were also extracted. The study retrospectively compared the relationship of SAS to postoperative complications and survival. Univariate analysis showed that postoperative complications were significantly associated with hypertension (p = 0.017), thoracotomy (p = 0.012), and SAS ≤ 5 (p < 0.0001), and multivariate analysis showed that hypertension (p = 0.049) and SAS ≤ 5 (p < 0.0001) were significant predictive factors for complications. In the prognostic analysis, log-rank analysis showed that patients with an SAS ≤ 5 had a significantly poorer prognosis than those with a SAS > 5 (p = 0.043), especially for complications classified as clinical stage 2 or higher (p = 0.027). In the multivariate analysis, SAS ≤ 5 was identified as a significantly poor prognostic factor for complications classified as clinical stage 2 or higher (p = 0.029). In this study, SAS was useful not only for predicting short-term complications, but also as a long-term prognostic factor after esophagectomy.
Nater, Anick; Martin, Allan R.; Sahgal, Arjun; Choi, David
2017-01-01
Purpose While several clinical prediction rules (CPRs) of survival exist for patients with symptomatic spinal metastasis (SSM), these have variable prognostic ability and there is no recognized CPR for health related quality of life (HRQoL). We undertook a critical appraisal of the literature to identify key preoperative prognostic factors of clinical outcomes in patients with SSM who were treated surgically. The results of this study could be used to modify existing or develop new CPRs. Methods Seven electronic databases were searched (1990–2015), without language restriction, to identify studies that performed multivariate analysis of preoperative predictors of survival, neurological, functional and HRQoL outcomes in surgical patients with SSM. Individual studies were assessed for class of evidence. The strength of the overall body of evidence was evaluated using GRADE for each predictor. Results Among 4,818 unique citations, 17 were included; all were in English, rated Class III and focused on survival, revealing a total of 46 predictors. The strength of the overall body of evidence was very low for 39 and low for 7 predictors. Due to considerable heterogeneity in patient samples and prognostic factors investigated as well as several methodological issues, our results had a moderately high risk of bias and were difficult to interpret. Conclusions The quality of evidence for predictors of survival was, at best, low. We failed to identify studies that evaluated preoperative prognostic factors for neurological, functional, or HRQoL outcomes in surgical patients with SSM. We formulated methodological recommendations for prognostic studies to promote acquiring high-quality evidence to better estimate predictor effect sizes to improve patient education, surgical decision-making and development of CPRs. PMID:28225772
Annunziata, Salvatore; Cuccaro, Annarosa; Tisi, Maria Chiara; Hohaus, Stefan; Rufini, Vittoria
2018-06-01
To retrospectively investigate the prognostic role of the ratio between target lesion and liver SUV max (rPET) in patients with follicular lymphoma (FL) submitted to FDG-PET/CT at the end of immuno-chemotherapy (PI-PET), and to compare rPET with International Harmonization Project criteria (IHP), Deauville Score (5p-DS) and FL International Prognostic Index at diagnosis (FLIPI). Eighty-nine patients with FL undergoing PI-PET were evaluated. The receiver operating characteristic (ROC) approach was applied to identify the optimal cut-point of rPET with respect to 5-years progression free survival (PFS). The prognostic significance of rPET was compared with IHP, DS and FLIPI. Positive predictive value (PPV) and negative predictive value (NPV) were calculated using the presence of adverse events as gold standard. The ROC analysis for rPET as predictor of progression showed an optimal rPET cut-point of 0.98. Patients with positive values of IHP, DS and rPET had a PFS of 50, 30 and 31%. PPV were of 56, 80 and 80%, NPV of 83, 86 and 88%, respectively. DS and rPET differed only in two patients. FLIPI was not predictive of progression and relapse. rPET is a prognostic factor in patients with FL submitted to PI-PET. Although it has a similar prognostic power as DS, it can have methodological advantages over visual analysis. PI-PET with different evaluation systems has a stronger prognostic power than FLIPI at diagnosis, so it could be useful to identify patients with FL at risk for early relapse after immuno-chemotherapy.
Oshiro, Yukio; Sasaki, Ryoko; Fukunaga, Kiyoshi; Kondo, Tadashi; Oda, Tatsuya; Takahashi, Hideto; Ohkohchi, Nobuhiro
2013-03-01
Recent studies have revealed that the Glasgow prognostic score (GPS), an inflammation-based prognostic score, is useful for predicting outcome in a variety of cancers. This study sought to investigate the significance of GPS for prognostication of patients who underwent surgery with extrahepatic cholangiocarcinoma. We retrospectively analyzed a total of 62 patients who underwent resection for extrahepatic cholangiocarcinoma. We calculated the GPS as follows: patients with both an elevated C-reactive protein (>10 mg/L) and hypoalbuminemia (<35 g/L) were allocated a score of 2; patients with one or none of these abnormalities were allocated a s ore of 1 or 0, respectively. Prognostic significance was analyzed by the log-rank test and a Cox proportional hazards model. Overall survival rate was 25.5 % at 5 years for all 62 patients. Venous invasion (p = 0.01), pathological primary tumor category (p = 0.013), lymph node metastasis category (p < 0.001), TNM stage (p < 0.001), and GPS (p = 0.008) were significantly associated with survival by univariate analysis. A Cox model demonstrated that increased GPS was an independent predictive factor with poor prognosis. The preoperative GPS is a useful predictor of postoperative outcome in patients with extrahepatic cholangiocarcinoma.
2013-01-01
Background People suffering from musculoskeletal shoulder pain are frequently referred to physiotherapy. Physiotherapy generally involves a multimodal approach to management that may include; exercise, manual therapy and techniques to reduce pain. At present it is not possible to predict which patients will respond positively to physiotherapy treatment. The purpose of this systematic review was to identify which prognostic factors are associated with the outcome of physiotherapy in the management of musculoskeletal shoulder pain. Methods A comprehensive search was undertaken of Ovid Medline, EMBASE, CINAHL and AMED (from inception to January 2013). Prospective studies of participants with shoulder pain receiving physiotherapy which investigated the association between baseline prognostic factors and change in pain and function over time were included. Study selection, data extraction and appraisal of study quality were undertaken by two independent assessors. Quality criteria were selected from previously published guidelines to form a checklist of 24 items. The study protocol was prospectively registered onto the International Prospective Register of Systematic Reviews. Results A total of 5023 titles were retrieved and screened for eligibility, 154 articles were assessed as full text and 16 met the inclusion criteria: 11 cohort studies, 3 randomised controlled trials and 2 controlled trials. Results were presented for the 9 studies meeting 13 or more of the 24 quality criteria. Clinical and statistical heterogeneity resulted in qualitative synthesis rather than meta-analysis. Three studies demonstrated that high functional disability at baseline was associated with poor functional outcome (p ≤ 0.05). Four studies demonstrated a significant association (p ≤ 0.05) between longer duration of shoulder pain and poorer outcome. Three studies, demonstrated a significant association (p ≤ 0.05) between increasing age and poorer function; three studies demonstrated no association (p > 0.05). Conclusion Associations between prognostic factors and outcome were often inconsistent between studies. This may be due to clinical heterogeneity or type II errors. Only two baseline prognostic factors demonstrated a consistent association with outcome in two or more studies; duration of shoulder pain and baseline function. Prior to developing a predictive model for the outcome of physiotherapy treatment for shoulder pain, a large adequately powered prospective cohort study is required in which a broad range of prognostic factors are incorporated. PMID:23834747
Setzer, Frank C; Boyer, Keith R; Jeppson, Joshua R; Karabucak, Bekir; Kim, Syngcuk
2011-01-01
Long-term predictability of restored endodontically treated teeth is important for the decision of tooth retention versus extraction and implant placement. The purpose of this study was to validate the hypothesis that preoperative factors can predict the long-term prognosis of molars requiring endodontic and restorative treatment for future prognostic investigations. A clinical database was searched for molar endodontic treatments with crown placement and a minimum of 4-year follow-up. Charts of 42 patients with 50 individual treatments were randomly selected. Information concerning crown lengthening; periodontal diagnosis; attachment loss; furcation involvement; mobility; and internal, external, or periradicular resorption was recorded. Radiographs from treatment initiation and follow-up were digitalized. The presence of apical periodontitis was evaluated. Available ferrule was calculated from bitewing radiographs using CAD software (AutoCAD; Autodesk, Cupertino, CA). The resulting data, age, sex, and times of restoration and follow-up were analyzed for correlation with the presence of apical radiolucency at follow-up and the following four possible outcome scenarios: "no event," "nonsurgical retreatment," "surgical retreatment," or "extraction" using Spearman rank order correlation analysis. Patients' ages ranged from 19 to 87 years, 22 were male and 20 female, and 48 teeth (96.0%) were retained at follow-up. Of those, 44 (88.0%) were without intervention ("no event"), and four (8.0%) underwent surgical or nonsurgical retreatment. Two teeth (4.0%) had been extracted. Significant positive correlations existed between "untoward events" (any form of retreatment or extraction) and "prognostic value according to periodontal status" (p = 0.047) and "attachment loss" (p = 0.042). The only preoperative factors significant for the prognosis of restored endodontically treated molars were related to periodontal prognostic value and attachment loss. It can be concluded that it may be difficult to predict the prognosis of molars in need for endodontic treatment and restoration from prognostic factors not related to periodontal disease. Copyright © 2011 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Louie, Alexander V., E-mail: Dr.alexlouie@gmail.com; Department of Radiation Oncology, London Regional Cancer Program, University of Western Ontario, London, Ontario; Department of Epidemiology, Harvard School of Public Health, Harvard University, Boston, Massachusetts
Purpose: A prognostic model for 5-year overall survival (OS), consisting of recursive partitioning analysis (RPA) and a nomogram, was developed for patients with early-stage non-small cell lung cancer (ES-NSCLC) treated with stereotactic ablative radiation therapy (SABR). Methods and Materials: A primary dataset of 703 ES-NSCLC SABR patients was randomly divided into a training (67%) and an internal validation (33%) dataset. In the former group, 21 unique parameters consisting of patient, treatment, and tumor factors were entered into an RPA model to predict OS. Univariate and multivariate models were constructed for RPA-selected factors to evaluate their relationship with OS. A nomogrammore » for OS was constructed based on factors significant in multivariate modeling and validated with calibration plots. Both the RPA and the nomogram were externally validated in independent surgical (n=193) and SABR (n=543) datasets. Results: RPA identified 2 distinct risk classes based on tumor diameter, age, World Health Organization performance status (PS) and Charlson comorbidity index. This RPA had moderate discrimination in SABR datasets (c-index range: 0.52-0.60) but was of limited value in the surgical validation cohort. The nomogram predicting OS included smoking history in addition to RPA-identified factors. In contrast to RPA, validation of the nomogram performed well in internal validation (r{sup 2}=0.97) and external SABR (r{sup 2}=0.79) and surgical cohorts (r{sup 2}=0.91). Conclusions: The Amsterdam prognostic model is the first externally validated prognostication tool for OS in ES-NSCLC treated with SABR available to individualize patient decision making. The nomogram retained strong performance across surgical and SABR external validation datasets. RPA performance was poor in surgical patients, suggesting that 2 different distinct patient populations are being treated with these 2 effective modalities.« less
Steenstra, Ivan A; Munhall, Claire; Irvin, Emma; Oranye, Nelson; Passmore, Steven; Van Eerd, Dwayne; Mahood, Quenby; Hogg-Johnson, Sheilah
2017-09-01
Purpose We systematically reviewed the evidence on factors that predict duration of sick leave in workers after 6 weeks low back pain (LBP) related sick leave. We hypothesized that different factors affect the duration of the leave depending on the time away from work. Methods The review occurred in seven phases: (1) developing the central question, (2) conducting the literature search, (3) identifying relevant publications, (4) quality appraisal, (5) data extraction, (6) evidence synthesis, and (7) knowledge translation. We searched for studies that reported episodes of LBP and sick leave that lasted more than 6 weeks. All included studies reported at least one prognostic factor where return to work was the outcome. Results We identified twenty-two relevant publications. The impact of pain, functional status and radiating pain seems to change with duration of work disability. Workers' recovery expectations remain important after 6 weeks. Modified duties are rarely studied in later phases of work disability. Depression/mental health did not appear to be an important factor in later phases. Workplace physical factors remain important. There is insufficient evidence that pain catastrophising and fear avoidance are predictive factors in later phases. There was moderate evidence for age in the later phases. Functional capacity and claim related factors were supported by some evidence. Discusion Physical demands in the workplace are preventing workers from getting back to work in a timely fashion across phases. The psychosocial work environment is understudied in later phases. Overall, we cannot conclude that prognostic factors change over time.
Oh, Sang Hoon; Park, Kyu Nam; Shon, Young-Min; Kim, Young-Min; Kim, Han Joon; Youn, Chun Song; Kim, Soo Hyun; Choi, Seung Pill; Kim, Seok Chan
2015-09-22
Modern treatments have improved the survival rate following cardiac arrest, but prognostication remains a challenge. We examined the prognostic value of continuous electroencephalography according to time by performing amplitude-integrated electroencephalography on patients with cardiac arrest receiving therapeutic hypothermia. We prospectively studied 130 comatose patients treated with hypothermia from September 2010 to April 2013. We evaluated the time to normal trace (TTNT) as a neurological outcome predictor and determined the prognostic value of burst suppression and status epilepticus, with a particular focus on their time of occurrence. Fifty-five patients exhibited a cerebral performance category score of 1 to 2. The area under the curve for TTNT was 0.97 (95% confidence interval, 0.92-0.99), and the sensitivity and specificity of TTNT<24 hours after resuscitation as a threshold for predicting good neurological outcome were 94.6% (95% confidence interval, 84.9%-98.9%) and 90.7% (95% confidence interval, 81.7%-96.2%), respectively. The threshold displaying 100% specificity for predicting poor neurological outcome was TTNT>36 hours. Burst suppression and status epilepticus predicted poor neurological outcome (positive predictive value of 98.3% and 96.4%, respectively). The combination of these factors predicted a negative outcome at a median of 6.2 hours after resuscitation (sensitivity and specificity of 92.0% and 96.4%, respectively). A TTNT<24 hours was associated with good neurological outcome. The lack of normal trace development within 36 hours, status epilepticus, and burst suppression were predictors of poor outcome. The combination of these negative predictors may improve their prognostic performance at an earlier stage. © 2015 The Authors.
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
Primary central nervous system lymphoma in immunocompetent individuals: a single center experience.
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.
Baars, Erik W; van der Hart, Onno; Nijenhuis, Ellert R S; Chu, James A; Glas, Gerrit; Draijer, Nel
2011-01-01
The purpose of this study was to develop an expertise-based prognostic model for the treatment of complex posttraumatic stress disorder (PTSD) and dissociative identity disorder (DID). We developed a survey in 2 rounds: In the first round we surveyed 42 experienced therapists (22 DID and 20 complex PTSD therapists), and in the second round we surveyed a subset of 22 of the 42 therapists (13 DID and 9 complex PTSD therapists). First, we drew on therapists' knowledge of prognostic factors for stabilization-oriented treatment of complex PTSD and DID. Second, therapists prioritized a list of prognostic factors by estimating the size of each variable's prognostic effect; we clustered these factors according to content and named the clusters. Next, concept mapping methodology and statistical analyses (including principal components analyses) were used to transform individual judgments into weighted group judgments for clusters of items. A prognostic model, based on consensually determined estimates of effect sizes, of 8 clusters containing 51 factors for both complex PTSD and DID was formed. It includes the clusters lack of motivation, lack of healthy relationships, lack of healthy therapeutic relationships, lack of other internal and external resources, serious Axis I comorbidity, serious Axis II comorbidity, poor attachment, and self-destruction. In addition, a set of 5 DID-specific items was constructed. The model is supportive of the current phase-oriented treatment model, emphasizing the strengthening of the therapeutic relationship and the patient's resources in the initial stabilization phase. Further research is needed to test the model's statistical and clinical validity.
Chen, Mao-Gen; Wang, Xiao-Ping; Ju, Wei-Qiang; Zhao, Qiang; Wu, Lin-Wei; Ren, Qing-Qi; Guo, Zhi-Yong; Wang, Dong-Ping; Zhu, Xiao-Feng; Ma, Yi; He, Xiao-Shun
2017-01-01
Objectives Elevated plasma fibrinogen (Fib) correlated with patient's prognosis in several solid tumors. However, few studies have illuminated the relationship between preoperative Fib and prognosis of HCC after liver transplantation. We aimed to clarify the prognostic value of Fib and whether the prognostic accuracy can be enhanced by the combination of Fib and neutrophil–lymphocyte ratio (NLR). Results Fib was correlated with Child-pugh stage, alpha-fetoprotein (AFP), size of largest tumor, macro- and micro-vascular invasion. Univariate analysis showed preoperative Fib, AFP, NLR, size of largest tumor, tumor number, macro- and micro- vascular invasion were significantly associated with disease-free survival (DFS) and overall survival (OS) in HCC patients with liver transplantation. After multivariate analysis, only Fib and macro-vascular invasion were independently correlated with DFS and OS. Survival analysis showed that preoperative Fib > 2.345 g/L predicted poor prognosis of patients HCC after liver transplantation. Preoperative Fib showed prognostic value in various subgroups of HCC. Furthermore, the predictive range was expanded by the combination of Fib and NLR. Materials and Methods Data were collected retrospectively from 130 HCC patients who underwent liver transplantation. Preoperative Fib, NLR and clinicopathologic variables were analyzed. The survival analysis was performed by the Kaplan-Meier method, and compared by the log-rank test. Univariate and multivariate analyses were performed to identify the prognostic factors for DFS and OS. Conclusions Preoperative Fib is an independent effective predictor of prognosis for HCC patients, higher levels of Fib predict poorer outcomes and the combination of Fib and NLR enlarges the prognostic accuracy of testing. PMID:27935864
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
Biomarkers improve mortality prediction by prognostic scales in community-acquired pneumonia.
Menéndez, R; Martínez, R; Reyes, S; Mensa, J; Filella, X; Marcos, M A; Martínez, A; Esquinas, C; Ramirez, P; Torres, A
2009-07-01
Prognostic scales provide a useful tool to predict mortality in community-acquired pneumonia (CAP). However, the inflammatory response of the host, crucial in resolution and outcome, is not included in the prognostic scales. The aim of this study was to investigate whether information about the initial inflammatory cytokine profile and markers increases the accuracy of prognostic scales to predict 30-day mortality. To this aim, a prospective cohort study in two tertiary care hospitals was designed. Procalcitonin (PCT), C-reactive protein (CRP) and the systemic cytokines tumour necrosis factor alpha (TNFalpha) and interleukins IL6, IL8 and IL10 were measured at admission. Initial severity was assessed by PSI (Pneumonia Severity Index), CURB65 (Confusion, Urea nitrogen, Respiratory rate, Blood pressure, > or = 65 years of age) and CRB65 (Confusion, Respiratory rate, Blood pressure, > or = 65 years of age) scales. A total of 453 hospitalised CAP patients were included. The 36 patients who died (7.8%) had significantly increased levels of IL6, IL8, PCT and CRP. In regression logistic analyses, high levels of CRP and IL6 showed an independent predictive value for predicting 30-day mortality, after adjustment for prognostic scales. Adding CRP to PSI significantly increased the area under the receiver operating characteristic curve (AUC) from 0.80 to 0.85, that of CURB65 from 0.82 to 0.85 and that of CRB65 from 0.79 to 0.85. Adding IL6 or PCT values to CRP did not significantly increase the AUC of any scale. When using two scales (PSI and CURB65/CRB65) and CRP simultaneously the AUC was 0.88. Adding CRP levels to PSI, CURB65 and CRB65 scales improves the 30-day mortality prediction. The highest predictive value is reached with a combination of two scales and CRP. Further validation of that improvement is needed.
Etcheverry, Amandine; Aubry, Marc; Idbaih, Ahmed; Vauleon, Elodie; Marie, Yannick; Menei, Philippe; Boniface, Rachel; Figarella-Branger, Dominique; Karayan-Tapon, Lucie; Quillien, Veronique; Sanson, Marc; de Tayrac, Marie; Delattre, Jean-Yves; Mosser, Jean
2014-01-01
Consistently reported prognostic factors for glioblastoma (GBM) are age, extent of surgery, performance status, IDH1 mutational status, and MGMT promoter methylation status. We aimed to integrate biological and clinical prognostic factors into a nomogram intended to predict the survival time of an individual GBM patient treated with a standard regimen. In a previous study we showed that the methylation status of the DGKI promoter identified patients with MGMT-methylated tumors that responded poorly to the standard regimen. We further evaluated the potential prognostic value of DGKI methylation status. 399 patients with newly diagnosed GBM and treated with a standard regimen were retrospectively included in this study. Survival modelling was performed on two patient populations: intention-to-treat population of all included patients (population 1) and MGMT-methylated patients (population 2). Cox proportional hazard models were fitted to identify the main prognostic factors. A nomogram was developed for population 1. The prognostic value of DGKI promoter methylation status was evaluated on population 1 and population 2. The nomogram-based stratification of the cohort identified two risk groups (high/low) with significantly different median survival. We validated the prognostic value of DGKI methylation status for MGMT-methylated patients. We also demonstrated that the DGKI methylation status identified 22% of poorly responding patients in the low-risk group defined by the nomogram. Our results improve the conventional MGMT stratification of GBM patients receiving standard treatment. These results could help the interpretation of published or ongoing clinical trial outcomes and refine patient recruitment in the future.
Ritter, Anne C; Wagner, Amy K; Szaflarski, Jerzy P; Brooks, Maria M; Zafonte, Ross D; Pugh, Mary Jo V; Fabio, Anthony; Hammond, Flora M; Dreer, Laura E; Bushnik, Tamara; Walker, William C; Brown, Allen W; Johnson-Greene, Doug; Shea, Timothy; Krellman, Jason W; Rosenthal, Joseph A
2016-09-01
Posttraumatic seizures (PTS) are well-recognized acute and chronic complications of traumatic brain injury (TBI). Risk factors have been identified, but considerable variability in who develops PTS remains. Existing PTS prognostic models are not widely adopted for clinical use and do not reflect current trends in injury, diagnosis, or care. We aimed to develop and internally validate preliminary prognostic regression models to predict PTS during acute care hospitalization, and at year 1 and year 2 postinjury. Prognostic models predicting PTS during acute care hospitalization and year 1 and year 2 post-injury were developed using a recent (2011-2014) cohort from the TBI Model Systems National Database. Potential PTS predictors were selected based on previous literature and biologic plausibility. Bivariable logistic regression identified variables with a p-value < 0.20 that were used to fit initial prognostic models. Multivariable logistic regression modeling with backward-stepwise elimination was used to determine reduced prognostic models and to internally validate using 1,000 bootstrap samples. Fit statistics were calculated, correcting for overfitting (optimism). The prognostic models identified sex, craniotomy, contusion load, and pre-injury limitation in learning/remembering/concentrating as significant PTS predictors during acute hospitalization. Significant predictors of PTS at year 1 were subdural hematoma (SDH), contusion load, craniotomy, craniectomy, seizure during acute hospitalization, duration of posttraumatic amnesia, preinjury mental health treatment/psychiatric hospitalization, and preinjury incarceration. Year 2 significant predictors were similar to those of year 1: SDH, intraparenchymal fragment, craniotomy, craniectomy, seizure during acute hospitalization, and preinjury incarceration. Corrected concordance (C) statistics were 0.599, 0.747, and 0.716 for acute hospitalization, year 1, and year 2 models, respectively. The prognostic model for PTS during acute hospitalization did not discriminate well. Year 1 and year 2 models showed fair to good predictive validity for PTS. Cranial surgery, although medically necessary, requires ongoing research regarding potential benefits of increased monitoring for signs of epileptogenesis, PTS prophylaxis, and/or rehabilitation/social support. Future studies should externally validate models and determine clinical utility. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.
Gastric biomarkers: a global review.
Baniak, Nick; Senger, Jenna-Lynn; Ahmed, Shahid; Kanthan, S C; Kanthan, Rani
2016-08-11
Gastric cancer is an aggressive disease with a poor 5-year survival and large global burden of disease. The disease is biologically and genetically heterogeneous with a poorly understood carcinogenesis at the molecular level. Despite the many prognostic, predictive, and therapeutic biomarkers investigated to date, gastric cancer continues to be detected at an advanced stage with resultant poor clinical outcomes. This is a global review of gastric biomarkers with an emphasis on HER2, E-cadherin, fibroblast growth factor receptor, mammalian target of rapamycin, and hepatocyte growth factor receptor as well as sections on microRNAs, long noncoding RNAs, matrix metalloproteinases, PD-L1, TP53, and microsatellite instability. A deeper understanding of the pathogenesis and biological features of gastric cancer, including the identification and characterization of diagnostic, prognostic, predictive, and therapeutic biomarkers, hopefully will provide improved clinical outcomes.
Asayama, Yoshiki; Nishie, Akihiro; Ishigami, Kousei; Ushijima, Yasuhiro; Takayama, Yukihisa; Okamoto, Daisuke; Fujita, Nobuhiro; Ohtsuka, Takao; Yoshizumi, Tomoharu; Aishima, Shinichi; Oda, Yoshinao; Honda, Hiroshi
2017-06-01
To determine whether washout characteristics of dynamic contrast-enhanced computed tomography (CT) could predict survival in patients with extrahepatic cholangiocarcinoma (EHC). This study collected 46 resected cases. All cases were examined by dynamic contrast study on multidetector-row CT. Region-of-interest measurements were obtained at the non-enhanced, portal venous phase and delayed phase in the tumour and were used to calculate the washout ratio as follows: [(attenuation value at portal venous phase CT - attenuation value at delayed enhanced CT)/(attenuation value at portal venous phase CT - attenuation value at unenhanced CT)] × 100. On the basis of the median washout ratio, we classified the cases into two groups, a high-washout group and low-washout group. Associations between overall survival and various factors including washout rates were analysed. The median washout ratio was 29.4 %. Univariate analysis revealed that a lower washout ratio, venous invasion, lymphatic permeation and lymph node metastasis were associated with shorter survival. Multivariate analysis identified the lower washout ratio as an independent prognostic factor (hazard ratio, 3.768; p value, 0.027). The washout ratio obtained from the contrast-enhanced CT may be a useful imaging biomarker for the prediction of survival of patients with EHC. • Dynamic contrast study can evaluate the aggressiveness of extrahepatic cholangiocarcinoma. • A lower washout ratio was an independent prognostic factor for overall survival. • CT can predict survival and inform decisions on surgical options or chemotherapy.
Nonoperative management of blunt hepatic trauma: A systematic review.
Boese, Christoph Kolja; Hackl, Michael; Müller, Lars Peter; Ruchholtz, Steffen; Frink, Michael; Lechler, Philipp
2015-10-01
Nonoperative management (NOM) has become the standard treatment in hemodynamically stable patients with blunt hepatic injuries. While the reported overall success rates of NOM are excellent, there is a lack of consensus regarding the risk factors predicting the failure of NOM. The aim of this systematic review was to identify the incidence and prognostic factors for failure of NOM in adult patients with blunt hepatic trauma. Prospective studies reporting prognostic factors for the failure of nonoperative treatment of blunt liver injuries were identified by searching MEDLINE and the Cochrane Central Register of Controlled Trials. We screened 798 titles and abstracts, of which 8 single-center prospective observational studies, reporting 410 patients, were included in the qualitative and quantitative synthesis. No randomized controlled trials were found. The pooled failure rate of NOM was 9.5% (0-24%). Twenty-six prognostic factors predicting the failure of NOM were reported, of which six reached statistical significance in one or more studies: blood pressure (p < 0.05), fluid resuscitation (p = 0.02), blood transfusion (p = 0.003), peritoneal signs (p < 0.0001), Injury Severity Score (ISS) (p = 0.03), and associated intra-abdominal injuries (p < 0.01). There is evidence that patients presenting with clinical signs of shock, a high ISS, associated intra-abdominal injuries, and peritoneal signs are at an increased risk of failure of NOM for the treatment of blunt hepatic injuries. Systematic review, level III.
Chen, Zhiqiang; Zhang, Long; Zhu, Qin; Wang, Xiaowei; Wu, Jindao; Wang, Xuehao
2017-03-01
The role of octamer-binding transcription factor 4 (Oct4) has been implicated in the clinical prognosis of various kinds of digestive system cancers, but the results remain controversial. The purpose of this meta-analysis is to assess the potential role of Oct4 as a prognostic marker in digestive system tumors. Relevant articles were retrieved from Pubmed, Web of Science, and Cochrane Library up to July 2016. The software Stata 12.0 was used to analyze the outcomes, including overall survival (OS), disease-free survival, recurrence-free survival, and clinicopathological characteristics. A total of 13 eligible studies with 1538 patients were included. Elevated Oct4 expression was significantly associated with poor OS (pooled hazard ratio [HR] = 2.183, 95% confidence interval [CI]: 1.824-2.612), disease-free survival (pooled HR = 1.973, 95% CI: 1.538-2.532), and recurrence-free survival (pooled HR = 2.209, 95% CI: 1.461-3.338) of digestive system malignancies. Subgroup analyses showed that cancer type, sample size, study quality, and laboratory detection method did not alter the significant prognostic value of Oct4. Additionally, Oct4 expression was found to be an independent predictive factor for OS (HR = 2.068, 95% CI: 1.633-2.619). No significant association was found between Oct4 and clinicopathological features of digestive system malignancies. This study provided evidence of Oct4 and/or its closely related homolog protein as a predictive factor for patients with digestive system cancers. More large-scale clinical studies on the prognostic value of Oct4 are warranted. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.
[Prognostic factors for in-hospital cardiopulmonary arrests. A review of 760 cases].
Fontanals, Jaume; Magaldi, Marta; Caballero, Ángel; Fontanals, Montserrat
2016-07-15
The aim of this study is to analyse in-hospital cardiopulmonary arrests (CA) that took place in conventional wards and evaluate their prognostic factors. Retrospective review of in-hospital CA which occurred in our hospital over a 9-year period. CA that took place in intensive care areas, emergency rooms and operating theatres were excluded from the study. The following data were collected: demographic data, cause and initial rhythm of CA, internal control data, time, place, methods and results after cardiopulmonary resuscitation (CPR) (recovery of spontaneous circulation, [ROSC], and survival at discharge [SAD]) and neurologic performance at discharge. Results were analysed with SPSS(®) v. 20 predictive analytics software. Average age was 66.9±17.5 years; 63.5% male. CA team arrived in 1.75±0.74min on average, and the average length of CPR was 25.8±16.10min. First rhythm: a) shockable rhythms=22.1%; b) asystole=66.2%, and c) pulseless electrical activity=11.7%. ROSC=51% and SAD=24.8%. Factors associated with a better prognostic (P<.05): age, reason for hospital admission, patient's previous physical condition, principal cause of CA, number of defibrillations and average length of CPR. Despite having studied several variables as prognostic factors for CA and some of them being statistically significant, early prediction for survival for an in-hospital CA remains uncertain. Our study suggests that applying rational organisational measures, 25% of in-hospital CA could be discharged from hospital in good condition, and therefore, these organisational and educational measures should be extended to large hospitals. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.
Impact of sex on prognostic host factors in surgical patients with lung cancer.
Wainer, Zoe; Wright, Gavin M; Gough, Karla; Daniels, Marissa G; Choong, Peter; Conron, Matthew; Russell, Prudence A; Alam, Naveed Z; Ball, David; Solomon, Benjamin
2017-12-01
Lung cancer has markedly poorer survival in men. Recognized important prognostic factors are divided into host, tumour and environmental factors. Traditional staging systems that use only tumour factors to predict prognosis are of limited accuracy. By examining sex-based patterns of disease-specific survival in non-small cell lung cancer patients, we determined the effect of sex on the prognostic value of additional host factors. Two cohorts of patients treated surgically with curative intent between 2000 and 2009 were utilized. The primary cohort was from Melbourne, Australia, with an independent validation set from the American Surveillance, Epidemiology and End Results (SEER) database. Univariate and multivariate analyses of validated host-related prognostic factors were performed in both cohorts to investigate the differences in survival between men and women. The Melbourne cohort had 605 patients (61% men) and SEER cohort comprised 55 681 patients (51% men). Disease-specific 5-year survival showed men had statistically significant poorer survival in both cohorts (P < 0.001); Melbourne men at 53.2% compared with women at 68.3%, and SEER 53.3% men and 62.0% women were alive at 5 years. Being male was independently prognostic for disease-specific mortality in the Melbourne cohort after adjustment for ethnicity, smoking history, performance status, age, pathological stage and histology (hazard ratio = 1.54, 95% confidence interval: 1.10-2.16, P = 0.012). Sex differences in non-small cell lung cancer are important irrespective of age, ethnicity, smoking, performance status and tumour, node and metastasis stage. Epidemiological findings such as these should be translated into research and clinical paradigms to determine the factors that influence the survival disadvantage experienced by men. © 2016 Royal Australasian College of Surgeons.
Wan, Guo-Xing; Chen, Ping; Cai, Xiao-Jun; Li, Lin-Jun; Yu, Xiong-Jie; Pan, Dong-Feng; Wang, Xian-He; Wang, Xuan-Bin; Cao, Feng-Jun
2016-01-15
The red cell distribution width (RDW) has also been reported to reliably reflect the inflammation and nutrition status and predict the prognosis across several types of cancer, however, the prognostic value of RDW in esophageal carcinoma has seldom been studied. A retrospective study was performed to assess the prognostic value of RDW in patients with esophageal carcinoma by the Kaplan-Meier analysis and multivariate Cox regression proportional hazard model. All enrolled patients were divided into high RDW group (≧15%) and low RDW group (<15%) according to the detected RDW values. Clinical and laboratory data from a total of 179 patients with esophageal carcinoma were retrieved. With a median follow-up of 21months, the high RDW group exhibited a shorter disease-free survival (DFS) (p<0.001) and an unfavorable overall survival (OS) (p<0.001) in the univariate analysis. The multivariate analysis revealed that elevated RDW at diagnosis was an independent prognostic factor for shorter PFS (p=0.043, HR=1.907, 95% CI=1.020-3.565) and poor OS (p=0.042, HR=1.895, 95% CI=1.023-3.508) after adjustment with other cancer-related prognostic factors. The present study suggests that elevated preoperative RDW(≧15%) at the diagnosis may independently predict poorer disease-free and overall survival among patients with esophageal carcinoma. Copyright © 2015 Elsevier B.V. All rights reserved.
Initial FDG-PET/CT predicts survival in adults Ewing sarcoma family of tumors
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
Usuda, Katsuo; Funasaki, Aika; Sekimura, Atsushi; Motono, Nozomu; Matoba, Munetaka; Doai, Mariko; Yamada, Sohsuke; Ueda, Yoshimichi; Uramoto, Hidetaka
2018-04-09
Diffusion-weighted magnetic resonance imaging (DWI) is useful for detecting malignant tumors and the assessment of lymph nodes, as FDG-PET/CT is. But it is not clear how DWI influences the prognosis of lung cancer patients. The focus of this study is to evaluate the correlations between maximum standardized uptake value (SUVmax) of FDG-PET/CT and apparent diffusion coefficient (ADC) value of DWI with known prognostic factors in resected lung cancer. A total of 227 patients with resected lung cancers were enrolled in this study. FEG-PET/CT and DWI were performed in each patient before surgery. There were 168 patients with adenocarcinoma, 44 patients with squamous cell carcinoma, and 15 patients with other cell types. SUVmax was a factor that was correlated to T factor, N factor, or cell differentiation. ADC of lung cancer was a factor that was not correlated to T factor, or N factor. There was a significantly weak inverse relationship between SUVmax and ADC (Correlation coefficient r = - 0.227). In analysis of survival, there were significant differences between the categories of sex, age, pT factor, pN factor, cell differentiation, cell type, and SUVmax. Univariate analysis revealed that SUVmax, pN factor, age, cell differentiation, cell type, sex, and pT factor were significant factors. Multivariate analysis revealed that SUVmax and pN factor were independent significant prognostic factors. SUVmax was a significant prognostic factor that is correlated to T factor, N factor, or cell differentiation, but ADC was not. SUVmax may be more useful for predicting the prognosis of lung cancer than ADC values.
Prognostic and predictive factors in colorectal cancer.
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.
Adelian, R.; Jamali, J.; Zare, N.; Ayatollahi, S. M. T.; Pooladfar, G. R.; Roustaei, N.
2015-01-01
Background: Identification of the prognostic factors for survival in patients with liver transplantation is challengeable. Various methods of survival analysis have provided different, sometimes contradictory, results from the same data. Objective: To compare Cox’s regression model with parametric models for determining the independent factors for predicting adults’ and pediatrics’ survival after liver transplantation. Method: This study was conducted on 183 pediatric patients and 346 adults underwent liver transplantation in Namazi Hospital, Shiraz, southern Iran. The study population included all patients undergoing liver transplantation from 2000 to 2012. The prognostic factors sex, age, Child class, initial diagnosis of the liver disease, PELD/MELD score, and pre-operative laboratory markers were selected for survival analysis. Result: Among 529 patients, 346 (64.5%) were adult and 183 (34.6%) were pediatric cases. Overall, the lognormal distribution was the best-fitting model for adult and pediatric patients. Age in adults (HR=1.16, p<0.05) and weight (HR=2.68, p<0.01) and Child class B (HR=2.12, p<0.05) in pediatric patients were the most important factors for prediction of survival after liver transplantation. Adult patients younger than the mean age and pediatric patients weighing above the mean and Child class A (compared to those with classes B or C) had better survival. Conclusion: Parametric regression model is a good alternative for the Cox’s regression model. PMID:26306158
Yang, Yu-Shang; Hu, Wei-Peng; Ni, Peng-Zhi; Wang, Wen-Ping; Yuan, Yong; Chen, Long-Qi
2017-06-27
Predictive value of preoperative endoscopic characteristic of esophageal tumor has not been fully evaluated. The aim of this study is to investigate the impact of esophageal luminal stenosis on survival for patients with resectable esophageal squamous cell carcinoma (ESCC). The clinicopathologic characteristics of 623 ESCC patients who underwent curative resection as the primary treatment between January 2005 and April 2009 were retrospectively reviewed. The esophageal luminal stenosis measured by endoscopy was defined as a uniform measurement preoperatively. The impact of esophageal luminal stenosis on patients' overall survival (OS) and relation with other clinicopathological features were assessed. A Cox regression model was used to identify prognostic factors. The results showed that OS significantly decreased in patients with manifest stenotic tumor compared with patients without luminal obstruction (P<0.05). Considerable esophageal luminal stenosis was associated with a higher T stage, longer tumor length, and poorer differentiation (all P<0.05). In multivariate survival analysis, esophageal luminal stenosis remained as an independent prognostic factor for OS (P= 0.036). Esophageal luminal stenosis could have a significant impact on the OS in patients with resected ESCC and may provide additional prognostic value to the current staging system before any cancer-specific treatment.
Feldman, Arthur M; Mann, Douglas L; She, Lilin; Bristow, Michael R; Maisel, Alan S; McNamara, Dennis M; Walsh, Ryan; Lee, Dorellyn L; Wos, Stanislaw; Lang, Irene; Wells, Gretchen; Drazner, Mark H; Schmedtje, John F; Pauly, Daniel F; Sueta, Carla A; Di Maio, Michael; Kron, Irving L; Velazquez, Eric J; Lee, Kerry L
2013-05-01
Patients with heart failure and coronary artery disease often undergo coronary artery bypass grafting, but assessment of the risk of an adverse outcome in these patients is difficult. To evaluate the ability of biomarkers to contribute independent prognostic information in these patients, we measured levels in patients enrolled in the biomarker substudies of the Surgical Treatment for Ischemic Heart Failure (STICH) trials. Patients in STICH Hypothesis 1 were randomized to medical therapy or coronary artery bypass grafting, whereas those in STICH Hypothesis 2 were randomized to coronary artery bypass grafting or coronary artery bypass grafting with left ventricular reconstruction. In substudy patients assigned to STICH Hypothesis 1 (n=606), plasma levels of soluble tumor necrosis factor-α receptor-1 (sTNFR-1) and brain natriuretic peptide (BNP) were highly predictive of the primary outcome variable of mortality by univariate analysis (BNP: χ(2)=40.6; P<0.0001 and sTNFR-1: χ(2)=38.9; P<0.0001). When considered in the context of multivariable analysis, both BNP and sTNFR-1 contributed independent prognostic information beyond the information provided by a large array of clinical factors independent of treatment assignment. Consistent results were seen when assessing the predictive value of BNP and sTNFR-1 in patients assigned to STICH Hypothesis 2 (n=626). Both plasma levels of BNP (χ(2)=30.3) and sTNFR-1 (χ(2)=45.5) were highly predictive in univariate analysis (P<0.0001) and in multivariable analysis for the primary end point of death or cardiac hospitalization. In multivariable analysis, the prognostic information contributed by BNP (χ(2)=6.0; P=0.049) and sTNFR-1 (χ(2)=8.8; P=0.003) remained statistically significant even after accounting for other clinical information. Although the biomarkers added little discriminatory improvement to the clinical factors (increase in c-index ≤0.1), net reclassification improvement for the primary end points was 0.29 for BNP and 0.21 for sTNFR-1 in the Hypothesis 1 cohort, and 0.15 for BNP and 0.30 for sTNFR-1 in the Hypothesis 2 cohort, reflecting important predictive improvement. Elevated levels of sTNFR-1 and BNP are strongly associated with outcomes, independent of therapy, in 2 large and independent studies, thus providing important cross-validation for the prognostic importance of these 2 biomarkers.
Mombelli, Sarah; Kwiatkowski, Fabrice; Abrial, Catherine; Wang-Lopez, Qian; de Boissieu, Paul; Garbar, Christian; Bensussan, Armand; Curé, Hervé
2015-01-01
Neoadjuvant chemotherapy (NACT) allows for a more frequent use of breast-conservative surgery; it is also an in vivo model of individual tumor sensitivity which permits to determine new prognostic factors to personalize the therapeutic approach. Between 2000 and 2012, 318 patients with primary invasive breast cancer were treated with a median of 6 cycles of NACT; they received either an anthracycline-based FEC 100 protocol (31.1%), or anthracyclines + taxanes (53.5%), with trastuzumab if indicated (15.4%). After a median follow-up of 44.2 months, the pathological complete response rate according to the classification of Chevallier et al. [Am J Clin Oncol 1993;16:223-228] was 19.3%, and overall (OS) and disease-free survival (DFS) at 10 years were 60.2 and 69.6%, respectively. Univariate analyses demonstrated that the Residual Disease in Breast and Nodes (RDBN) index was the most significant prognostic factor for OS (p = 0.0082) and DFS (p = 0.0022), and multivariate analyses mainly revealed that the residual tumor size, residual involved node number and post-chemotherapy Scarff-Bloom-Richardson (SBR) grading were the most significant prognostic factors. In a cohort of patients who were all homogeneously treated with some of the most common drugs for breast cancer, we demonstrate that NACT may provide additional prognostic factors and confirm the RDBN index. As this index allows for the prediction of survival with different breast cancer subtypes, we suggest that it should be calculated routinely to help clinicians to select patients who need adjuvant treatments. 2015 S. Karger AG, Basel
Driver, Robert J; Handforth, Catherine; Radhakrishna, Ganesh; Bennett, Michael I; Ford, Alexander C; Everett, Simon M
2018-03-01
Optimizing the timing of esophageal stent insertion is a challenge, partly due to difficulty predicting survival in advanced malignancy. The Glasgow prognostic score (GPS) is a validated tool for predicting survival in a number of cancers. To assess the utility of the GPS in predicting 30-day mortality and overall survival postesophageal stent insertion. Patients at a tertiary referral center who had received an esophageal stent for palliation of dysphagia were included if they had a measurement of albumin and C-reactive protein (CRP) in the week preceding the procedure (n=209). Patients with both an elevated CRP (>10 mg/L) and hypoalbuminemia (<35 g/L) were given a GPS score of 2 (GPS2). Patients with only one of these abnormalities were assigned as GPS1 and those with normal CRP and albumin were assigned as GPS0. Clinical and pathologic parameters were also collected to assess for potential confounding factors in the survival analysis. Increasing GPS was associated with 30-day mortality; for patients with GPS0, 30-day mortality was 5% (2/43), for GPS1 it was 23% (26/114), and for GPS2 it was 33% (17/52). The adjusted hazard ratio for overall poststent mortality was 1.6 (95% confidence interval, 1.1-2.4; P=0.02) for GPS1 and 2.4 (95% confidence interval, 1.5-3.8; P<0.001) for GPS2 patients compared with GPS0. GPS is an independent prognostic factor of 30-day mortality and overall survival after esophageal stent insertion. It is a potential adjunct to clinical assessment in identifying those patients at high-risk of short-term mortality poststent.
Bolatkale, Mustafa; Acara, Ahmet Cagdas
2018-06-02
Penetrating brain injury (PBI) is the most lethal form of traumatic brain injury, which is a leading cause of mortality. PBI has a mortality rate of 23%-93% and 87%-100% with poor neurological status. Despite the use of various prognostic factors there is still a need for a specific prognostic factor for early prediction of mortality in PBI to reduce mortality and provide good outcomes with cost-effective surgical treatments. The aim of this study was to investigate the predictive value of the number of intracranial foreign bodies (FBs) on mortality in PBI in the Emergency Department. The study included 95 patients admitted with PBI caused by barrel bomb explosion. The intracranial number of FB was examined by brain computed tomography. Logistic regression was used to assess the association of the intracranial number of FB on mortality. Correlation analyses were performed to investigate the association of Glasgow Coma Scale (GCS) with intracranial number of FB. The optimal cut-off value of the intracranial number of FB calculated for mortality was 2, which was effective for predicting mortality (p < .001). In patients with >2 intracranial FB, the mortality rate was statistically significantly 51-fold higher than those with ≤2 (p < .001). A statistically significant negative correlation was determined between GCS and number of. FB (r = -0.697;p < .001). When the intracranial number of FB was >2, mortality significantly increased in patients with PBI. The intracranial number of FBs may be considered as a novel prognostic factor for the prediction of mortality in PBI. Penetrating brain injury, mortality, foreign body, barrel bomb. Copyright © 2018 Elsevier Inc. All rights reserved.
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.
Prognostic value of tumor necrosis at CT in diffuse large B-cell lymphoma.
Adams, Hugo J A; de Klerk, John M H; Fijnheer, Rob; Dubois, Stefan V; Nievelstein, Rutger A J; Kwee, Thomas C
2015-03-01
To determine the prognostic value of tumor necrosis at computed tomography (CT) in newly diagnosed diffuse large B-cell lymphoma (DLBCL). This retrospective study included 51 patients with newly diagnosed DLBCL who had undergone both unenhanced and intravenous contrast-enhanced CT before R-CHOP (rituximab, cyclophosphamide, hydroxydaunorubicin, oncovin and prednisolone) chemo-immunotherapy. Presence of tumor necrosis was visually and quantitatively assessed at CT. Associations between tumor necrosis status at CT and the National Comprehensive Cancer Network (NCCN) International Prognostic Index (IPI) factors were assessed. Cox regression analysis was used to determine the prognostic impact of NCCN-IPI scores and tumor necrosis status at CT. There were no correlations between tumor necrosis status at CT and the NCCN-IPI factors categorized age (ρ=-0.042, P=0.765), categorized lactate dehydrogenase (LDH) ratio (ρ=0.201, P=0.156), extranodal disease in major organs (φ=-0.245, P=0.083), Ann Arbor stage III/IV disease (φ=-0.208, P=0.141), and Eastern Cooperative Oncology Group (ECOG) performance status (φ=0.015, P=0.914). In the multivariate Cox proportional hazards model, only tumor necrosis status at CT was an independent predictive factor of progression-free survival (P=0.003) and overall survival (P=0.004). The findings of this study indicate the prognostic potential of tumor necrosis at CT in newly diagnosed DLBCL. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
Wang, L; Cai, L; Chen, Q; Jiang, Y H
2017-10-23
Objective: To evaluate the prognostic value of three different staging schemes based on positive lymph nodes (pN), metastatic lymph nodes ratio (MLR) and log odds of positive lymph nodes (LODDS) in patients with T3 esophageal cancer. Methods: From 2007 to 2014, clinicopathological characteristics of 905 patients who were pathologically diagnosed as T3 esophageal cancer and underwent radical esophagectomy in Zhejiang Cancer Hospital were retrospectively analyzed. Kaplan-Meier curves and Multivariate Cox proportional hazards models were used to evaluate the independent prognostic factors. The values of three lymph node staging schemes for predicting 5-year survival were analyzed by using receiver operating characteristic (ROC) curves. Results: The 1-, 3- and 5-year overall survival rates of patients with T3 esophageal cancer were 80.9%, 50.0% and 38.4%, respectively. Multivariate analysis showed that MLR stage, LODDS stage and differentiation were independent prognostic survival factors ( P <0.05 for all). ROC curves showed that the area under the curve of pN stage, MLR stage, LODDS stage was 0.607, 0.613 and 0.618, respectively. However, the differences were not statistically significant ( P >0.05). Conclusions: LODDS is an independent prognostic factor for patients with T3 esophageal cancer. The value of LODDS staging system may be superior to pN staging system for evaluating the prognosis of these patients.
Kim, Hyungjin; Park, Sang Joon; Kim, Miso; Kim, Tae Min; Kim, Dong-Wan; Heo, Dae Seog; Goo, Jin Mo
2017-01-01
Purpose To determine if the radiomic features on CT can predict progression-free survival (PFS) in epidermal growth factor receptor (EGFR) mutant adenocarcinoma patients treated with first-line EGFR tyrosine kinase inhibitors (TKIs) and to identify the incremental value of radiomic features over conventional clinical factors in PFS prediction. Methods In this institutional review board–approved retrospective study, pretreatment contrast-enhanced CT and first follow-up CT after initiation of TKIs were analyzed in 48 patients (M:F = 23:25; median age: 61 years). Radiomic features at baseline, at 1st first follow-up, and the percentage change between the two were determined. A Cox regression model was used to predict PFS with nonredundant radiomic features and clinical factors, respectively. The incremental value of radiomic features over the clinical factors in PFS prediction was also assessed by way of a concordance index. Results Roundness (HR: 3.91; 95% CI: 1.72, 8.90; P = 0.001) and grey-level nonuniformity (HR: 3.60; 95% CI: 1.80, 7.18; P<0.001) were independent predictors of PFS. For clinical factors, patient age (HR: 2.11; 95% CI: 1.01, 4.39; P = 0.046), baseline tumor diameter (HR: 1.03; 95% CI: 1.01, 1.05; P = 0.002), and treatment response (HR: 0.46; 95% CI: 0.24, 0.87; P = 0.017) were independent predictors. The addition of radiomic features to clinical factors significantly improved predictive performance (concordance index; combined model = 0.77, clinical-only model = 0.69, P<0.001). Conclusions Radiomic features enable PFS estimation in EGFR mutant adenocarcinoma patients treated with first-line EGFR TKIs. Radiomic features combined with clinical factors provide significant improvement in prognostic performance compared with using only clinical factors. PMID:29099855
Kammerer-Jacquet, Solène-Florence; Brunot, Angelique; Bensalah, Karim; Campillo-Gimenez, Boris; Lefort, Mathilde; Bayat, Sahar; Ravaud, Alain; Dupuis, Frantz; Yacoub, Mokrane; Verhoest, Gregory; Peyronnet, Benoit; Mathieu, Romain; Lespagnol, Alexandra; Mosser, Jean; Edeline, Julien; Laguerre, Brigitte; Bernhard, Jean-Christophe; Rioux-Leclercq, Nathalie
2017-10-01
The selection of patients with metastatic clear cell renal cell carcinoma (ccRCC) who may benefit from targeted tyrosine kinase inhibitors has been a challenge, even more so now with the advent of new therapies. Hilar fat infiltration (HFI) is a validated prognostic factor in nonmetastatic ccRCC (TNM 2009 staging system) but has never been studied in metastatic patients. We aimed to assess its phenotype and prognostic effect in patients with metastatic ccRCC treated with first-line sunitinib. In a multicentric study, we retrospectively included 90 patients and studied the corresponding ccRCC at the pathological, immunohistochemical, and molecular levels. Patient and tumor characteristics were compared using univariate and multivariate analysis. All the features were then studied by Cox models for prognostic effect. HFI was found in 42 patients (46.7%), who had worse prognosis (Heng criteria) (P = 0.003), liver metastases (P = 0.036), and progressive diseases at first radiological evaluation (P = 0.024). The corresponding ccRCC was associated with poor pathological prognostic factors that are well known in nonmetastatic ccRCC. For these patients, median progression-free survival was 4 months vs. 13 months (P = 0.02), and median overall survival was 14 months vs. 29 months (P = 0.006). In a multivariate Cox model integrating all the variables, only poor prognosis, according to the Heng criteria and HFI, remained independently associated with both progression-free survival and overall survival. HFI was demonstrated for the first time to be an independent poor prognostic factor. Its potential role in predicting resistance to antiangiogenic therapy warrants further investigation. Copyright © 2017 Elsevier Inc. All rights reserved.
CRC-113 gene expression signature for predicting prognosis in patients with colorectal cancer
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.
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.
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
Prognostic Significance of BMI-1 But Not MEL-18 Expression in Pulmonary Squamous Cell Carcinoma.
Abe, Sosei; Yamashita, Shin-Ichi; Miyahara, S O; Wakahara, Junichi; Yamamoto, Leona; Mori, Ryo; Imamura, Naoko; Yoshida, Yasuhiro; Waseda, Ryuichi; Hiratsuka, Masafumi; Shiraishi, Takeshi; Nabeshima, Kazuki; Iwasaki, Akinori
2017-04-01
We investigated the possibility of BMI-1 and MEL-18 to predict survival in patients with pulmonary squamous cell carcinoma. One hundred and ninety-nine patients underwent surgery in our Institute between 1995 and 2005. We used immunohistochemical (IHC) analysis to determine the expressions of BMI-1 and MEL-18 and compared them with clinicopathological factors and survival. Forty-one of 199 cases (21%) were BMI-1-positive. No correlation was found between BMI-1 and MEL-18 expression by IHC and clinicopathological factors. Five-year overall survival in the BMI-1-positive group (66.8%), but not MEL-18, was significantly better than that in the negative group (45.5%, p=0.04). In multivariate analysis, positive BMI-1 was a better prognostic factor of overall survival (hazard ratio (HR)=0.561, 95% confidence interval (CI)=0.271-1.16, p=0.12). BMI-1 expression, but not MEL-18, is associated with a favorable prognosis and is a possible prognostic factor of pulmonary squamous cell carcinoma. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
NASA Technical Reports Server (NTRS)
Daigle, Matthew J.; Sankararaman, Shankar
2013-01-01
Prognostics is centered on predicting the time of and time until adverse events in components, subsystems, and systems. It typically involves both a state estimation phase, in which the current health state of a system is identified, and a prediction phase, in which the state is projected forward in time. Since prognostics is mainly a prediction problem, prognostic approaches cannot avoid uncertainty, which arises due to several sources. Prognostics algorithms must both characterize this uncertainty and incorporate it into the predictions so that informed decisions can be made about the system. In this paper, we describe three methods to solve these problems, including Monte Carlo-, unscented transform-, and first-order reliability-based methods. Using a planetary rover as a case study, we demonstrate and compare the different methods in simulation for battery end-of-discharge prediction.
Noguchi, M; Kido, Y; Kubota, H; Kinjo, H; Kohama, G
1999-12-01
The records of 136 patients with N1-3 oral squamous cell carcinoma treated by surgery were investigated retrospectively, with the aim of finding out which factors were predictive of survival on multivariate analysis. Four independent factors significantly influenced survival in the following order: pN stage; T stage; histological grade; and N stage. The most significant was pN stage, the five-year survival for patients with pN0 being 91% and for patients with pN1-3 41%. A further study was carried out on the 80 patients with pN1-3 to find out their prognostic factors for survival and the independent factors identified by multivariate analysis were T stage and presence or absence of extracapsular spread to metastatic lymph nodes.
miR-185 is an independent prognosis factor and suppresses tumor metastasis in gastric cancer.
Tan, Zhiqin; Jiang, Hao; Wu, Youhua; Xie, Liming; Dai, Wenxiang; Tang, Hailin; Tang, Sanyuan
2014-01-01
miR-185 has been identified as an important factor in several cancers such as breast cancer, ovarial cancer, and prostate cancer. However, its effect and prognostic value in gastric cancer are still poorly known. In this study, we found that the expression levels of miR-185 were strongly downregulated in gastric cancer and associated with clinical stage and the presence of lymph node metastases. Moreover, miR-185 might independently predict OS and RFS in gastric cancer. We further found that upregulation of miR-185 inhibited the proliferation and metastasis of gastric cancer cells in vitro and in vivo. Taken together, our findings demonstrate that the miR-185 is important for gastric cancer initiation and progression and holds promise as a prognostic biomarker to predict survival and relapse in gastric cancer. It is also a potential therapeutic tool to improve clinical outcomes in the above disease.
Specific prognostic factors for secondary pancreatic infection in severe acute pancreatitis.
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.
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
Lakatos, Laszlo; Mester, Gabor; Reti, Gyorgy; Nagy, Attila; Lakatos, Peter Laszlo
2004-01-01
AIM: The optimal treatment for bile duct stones (in terms of cost, complications and accuracy) is unclear. The aim of our study was to determine the predictive factors for preoperative endoscopic retrograde cholangiopancreatography (ERCP). METHODS: Patients undergoing preoperative ERCP ( ≤ 90 d before laparoscopic cholecystectomy) were evaluated in this retrospective study from the 1st of January 1996 to the 31st of December 2002. The indications for ERCP were elevated serum bilirubin, elevated liver function tests (LFT), dilated bile duct ( ≥ 8 mm) and/or stone at US examination, coexisting acute pancreatitis and/or acute pancreatitis or jaundice in patient’s history. Suspected prognostic factors and the combination of factors were compared to the result of ERCP. RESULTS: Two hundred and six preoperative ERCPs were performed during the observed period. The rate of successful cannulation for ERC was (97.1%). Bile duct stones were detected in 81 patients (39.3%), and successfully removed in 79 (97.5%). The number of prognostic factors correlated with the presence of bile duct stones. The positive predictive value for one prognostic factor was 1.2%, for two 43%, for three 72.5%, for four or more 91.4%. CONCLUSION: Based on our data preoperative ERCP is highly recommended in patients with three or more positive factors (high risk patients). In contrast, ERCP is not indicated in patients with zero or one factor (low risk patients). Preoperative ERCP should be offered to patients with two positive factors (moderate risk patients), however the practice should also be based on the local conditions (e.g. skill of the endoscopist, other diagnostic tools). PMID:15526372
Skoczylas, Michał; Laudański, Tadeusz
2003-10-01
Cardiotocography has become the standard for fetal monitoring in labor. False-positive findings during electronic fetal heart rate monitoring may were not associated with neonatal acidemia. Because of the poor specificity of fetal heart rate monitoring in predicting fetal distress, new methods are being investigated as a way to improve the accuracy of assessing the infant's condition during labor. The aim of this study was to determinate the efficiency of fetal blood oxygen saturation (FSpO2) and computer analysis of the fetal heart rate (Co-CTG) in the late 1-st stage of labor as a prognostic factor of newborn acidemia. Total 62 subjects were studied. During labors and deliveries fetal oxygen saturation was continuously recorded, with use of Nellecor N-400 fetal pulse oximeter and continous CTG were performed by Hewlett Packard 50A. Transdermal fetal oxygen saturation measurements and CTG results obtained during the labors was analyzed using MONAKO system (ITAM Zabrze). The results were compared with the values of pH and base deficit in the umbilical artery measured just after delivery. The sensitivity, specificity, negative, positive predictive values and Youden factor based on FHR and FSpO2, for prognosis of neonatal acidosis were: 65%, 80%, 16%, 97.5% 60% and 0.135 respectively FHR; and 100%, 60%, 100%, 96.8% and 0.968 respectively FSpO2. 1. The examination of fetal blood oxygen saturation in the labor is a useful prognostic factor of the newborn outcome. 2. The best predictive value for intrapartum fetal asphyxia with metabolic acidosis was found when fetal pulse oximetry is added to cardiotocography.
Puustinen, Lauri; Boyd, Sonja; Mustonen, Harri; Arkkila, Perttu; Arola, Johanna; Färkkilä, Martti
2017-03-01
In autoimmune hepatitis, data on the prognostic value of baseline liver biopsy and the sequential histology is controversial. Our aim was to evaluate the prognostic value of clinical variables and biopsy at the time of diagnosis and during the disease course. All 98 patients in our hospital during 1995-2012 were included. Sequential biopsies were available in 66 patients. Analyses based on clinical and histological variables were performed to find parameters predicting the progression of fibrosis, and development of cirrhosis. At the time of diagnosis, 7% were cirrhotic. Fibrosis progressed in 28 (42%) patients, remained stable in 26 (39%) and resolved in 12 (18%) patients. Findings which predicted fibrosis progression, were baseline total inflammation (odds ratio 1.7, 95% CI 1.01-2.8), cumulative total inflammation (1.8, 95% CI 1.01-3.2, rosette formation (2.8, 95% CI 1.1-7.1), absence of pericholangitis (0.4, 95% CI 0.1-1.0) and necrosis (1.4, 95% CI 1.0-2.0). Risk factors for the development of cirrhosis were cholestasis (4.6, 95% CI 1.2-16.9), interphase inflammation (3.4, 95% CI 1.1-10.4), and necrosis (3.3, 95% CI 1.2-9.7). In a cumulative model, cumulative total inflammation (4.5, 95% CI 1.4-15.0), necrosis (6.7, 95% CI 1.3-34.6), or cumulative immunoglobulin G load (61.8, 95% CI 2.0-1954.3) were risk factors. None of the patients with histological pericholangitis or granulomas developed cirrhosis. The histology provides prognostic information regarding progression of fibrosis or the development of cirrhosis. The total cumulative inflammatory activity predicts the progression of fibrosis, whereas baseline fibrosis, interphase inflammation, cholestasis, necrosis, as well as the cumulative total inflammation and cumulative immunoglobulin G, are risk factors for cirrhosis.
Wang, F; Li, H; Tan, P H; Chua, E T; Yeo, R M C; Lim, F L W T; Kim, S W; Tan, D Y H; Wong, F Y
2014-11-01
At our centre, ductal carcinoma in situ (DCIS) was commonly treated with breast-conservation therapy (BCT). Local recurrence after BCT is a major concern. The aims of our study were to review the outcomes of DCIS treatment in our patients and to evaluate a nomogram from Memorial Sloan Kettering Cancer Centre (MSKCC) for predicting ipsilateral breast tumour recurrence (IBTR) in our Asian population. Chart reviews of 716 patients with pure DCIS treated from 1992 to 2011 were carried out. Univariable Cox regression analyses were used to evaluate the effects of the 10 prognostic factors of the MSKCC nomogram on IBTR. We constructed a separate National Cancer Centre Singapore (NCCS) nomogram based on multivariable Cox regression via reduced model selection by applying the stopping rule of Akaike's information criterion to predict IBTR-free survival. The abilities of the NCCS nomogram and the MSKCC nomogram to predict IBTR of individual patients were evaluated with bootstrapping of 200 sets of resamples and the NCCS dataset, respectively. Harrell's c-index was calculated for each nomogram to evaluate the concordance between predicted and observed responses of individual subjects. Study patients were followed up for a median of 70 months. Over 95% of patients received adjuvant radiotherapy. The 5 and 10 year actuarial IBTR-free survival rates for the cohort were 95.5 and 92.6%, respectively. In the multivariate analysis, independent prognostic factors for IBTR included use of adjuvant endocrine therapy, presence of comedonecrosis and younger age at diagnosis. These factors formed the basis of the NCCS nomogram, which had a similar c-index (NCCS: 0.696; MSKCC: 0.673) compared with the MSKCC nomogram. The MSKCC nomogram was validated in an Asian population. A simpler NCCS nomogram using a different combination of fewer prognostic factors may be sufficient for the prediction of IBTR in Asians, but requires external validation to compare for relative performance. Copyright © 2014 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
Prognostics Uncertainty Management with Application to Government and Industry
NASA Technical Reports Server (NTRS)
Celaya, Jose; Sankararaman, Shankar; Daigle, Matthew; Saxena, Abhinav; Goebel, Kai
2014-01-01
Predictions about the future are contingent on future usage, but also on the quality of the models employed and the assessment of the current health state. These factors, amongst others, need to be considered to arrive at a prediction that is conducted through a rigorous method but where the confidence bounds are not prohibitively large.
Inhalation injury in a burn unit: a retrospective review of prognostic factors
Monteiro, D.; Silva, I.; Egipto, P.; Magalhães, A.; Filipe, R.; Silva, A.; Rodrigues, A.; Costa, J.
2017-01-01
Summary Inhalation injury (InI) is known to seriously affect the prognosis of burn patients, as it is strongly associated with high morbidity and mortality. Despite major advances in the treatment of burn patients in the past years, advances in the treatment of smoke InI have been somewhat limited; mortality reduction mostly results from improvements in critical care. It is difficult to separate the contribution of InI from other mechanisms that also affect respiratory tract and lungs. The aim of this study was to compare patients with and without InI and to identify prognostic factors among patients with smoke InI. Patients with InI displayed higher total body surface area (TBSA) burned, higher incidence of pneumonia and acute respiratory distress syndrome (ARDS), a higher rate of positive blood cultures and a significantly higher death rate. We could conclude that older age, higher TBSA, ARDS and pneumonia were independent predictive factors for mortality in our global study population. Older age and higher TBSA were the only independent factors found to be predictive of mortality in patients with InI. PMID:29021724
Inhalation injury in a burn unit: a retrospective review of prognostic factors.
Monteiro, D; Silva, I; Egipto, P; Magalhães, A; Filipe, R; Silva, A; Rodrigues, A; Costa, J
2017-06-30
Inhalation injury (InI) is known to seriously affect the prognosis of burn patients, as it is strongly associated with high morbidity and mortality. Despite major advances in the treatment of burn patients in the past years, advances in the treatment of smoke InI have been somewhat limited; mortality reduction mostly results from improvements in critical care. It is difficult to separate the contribution of InI from other mechanisms that also affect respiratory tract and lungs. The aim of this study was to compare patients with and without InI and to identify prognostic factors among patients with smoke InI. Patients with InI displayed higher total body surface area (TBSA) burned, higher incidence of pneumonia and acute respiratory distress syndrome (ARDS), a higher rate of positive blood cultures and a significantly higher death rate. We could conclude that older age, higher TBSA, ARDS and pneumonia were independent predictive factors for mortality in our global study population. Older age and higher TBSA were the only independent factors found to be predictive of mortality in patients with InI.
Long-term follow-up of functional hypothalamic amenorrhea and prognostic factors.
Falsetti, Leopoldo; Gambera, Alessandro; Barbetti, Lorena; Specchia, Cristina
2002-02-01
This study evaluated the prognosis of functional hypothalamic amenorrhea (FHA) and the predictive factors of recovery, through a long-term follow-up. Ninety-three women affected by FHA underwent a follow-up for an average period of 8.1 yr (range 7-9 yr). At the end of the follow-up, 65 (70.7%) patients recovered. Statistical analysis showed that there was no association between recovery and anamnestic causes of FHA or with the echographic ovarian morphology but identified the predictive factors of recovery as the basal body mass index (BMI), the basal cortisol, and androstenedione plasma levels. A higher basal BMI and A, and lower cortisol values are positive prognostic factors for the recovery. Also the BMI, acquired during the follow-up, is important for FHA resolution: in fact, in recovered women the BMI increased or remained stable, whereas in nonrecovered women it decreased or remained stable. At the end of the follow-up, 52 (74.3%) patients treated with hormone replacement therapy and 8 (80%) with no therapy recovered, but only 5 (41.7%) with oral contraceptive pills recovered.
Lowes, L E; Lock, M; Rodrigues, G; D'Souza, D; Bauman, G; Ahmad, B; Venkatesan, V; Allan, A L; Sexton, T
2015-01-01
Background: Following radical prostatectomy, success of adjuvant and salvage radiation therapy (RT) is dependent on the absence of micrometastatic disease. However, reliable prognostic/predictive factors for determining this are lacking. Therefore, novel biomarkers are needed to assist with clinical decision-making in this setting. Enumeration of circulating tumor cells (CTCs) using the regulatory-approved CellSearch System (CSS) is prognostic in metastatic prostate cancer. We hypothesize that CTCs may also be prognostic in the post-prostatectomy setting. Methods: Patient blood samples (n=55) were processed on the CSS to enumerate CTCs at 0, 6, 12 and 24 months after completion of RT. CTC values were correlated with predictive/prognostic factors and progression-free survival. Results: CTC status (presence/absence) correlated significantly with positive margins (increased likelihood of CTCneg disease; P=0.032), and trended toward significance with the presence of seminal vesicle invasion (CTCpos; P=0.113) and extracapsular extension (CTCneg; P=0.116). Although there was a trend toward a decreased time to biochemical failure (BCF) in baseline CTC-positive patients (n=9), this trend was not significant (hazard ratio (HR)=0.3505; P=0.166). However, CTC-positive status at any point (n=16) predicted for time to BCF (HR=0.2868; P=0.0437). Conclusions: One caveat of this study is the small sample size utilized (n=55) and the low number of patients with CTC-positive disease (n=16). However, our results suggest that CTCs may be indicative of disseminated disease and assessment of CTCs during RT may be helpful in clinical decision-making to determine, which patients may benefit from RT versus those who may benefit more from systemic treatments. PMID:26238233
Wishart, Gordon C; Azzato, Elizabeth M; Greenberg, David C; Rashbass, Jem; Kearins, Olive; Lawrence, Gill; Caldas, Carlos; Pharoah, Paul D P
2010-01-01
The aim of this study was to develop and validate a prognostication model to predict overall and breast cancer specific survival for women treated for early breast cancer in the UK. Using the Eastern Cancer Registration and Information Centre (ECRIC) dataset, information was collated for 5,694 women who had surgery for invasive breast cancer in East Anglia from 1999 to 2003. Breast cancer mortality models for oestrogen receptor (ER) positive and ER negative tumours were derived from these data using Cox proportional hazards, adjusting for prognostic factors and mode of cancer detection (symptomatic versus screen-detected). An external dataset of 5,468 patients from the West Midlands Cancer Intelligence Unit (WMCIU) was used for validation. Differences in overall actual and predicted mortality were <1% at eight years for ECRIC (18.9% vs. 19.0%) and WMCIU (17.5% vs. 18.3%) with area under receiver-operator-characteristic curves (AUC) of 0.81 and 0.79 respectively. Differences in breast cancer specific actual and predicted mortality were <1% at eight years for ECRIC (12.9% vs. 13.5%) and <1.5% at eight years for WMCIU (12.2% vs. 13.6%) with AUC of 0.84 and 0.82 respectively. Model calibration was good for both ER positive and negative models although the ER positive model provided better discrimination (AUC 0.82) than ER negative (AUC 0.75). We have developed a prognostication model for early breast cancer based on UK cancer registry data that predicts breast cancer survival following surgery for invasive breast cancer and includes mode of detection for the first time. The model is well calibrated, provides a high degree of discrimination and has been validated in a second UK patient cohort.
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.
Takahashi, Goro; Yamada, Takeshi; Kan, Hayato; Koizumi, Michihiro; Shinji, Seiichi; Yokoyama, Yasuyuki; Iwai, Takuma; Uchida, Eiji
2015-10-01
Skeletal mass depletion has been reported to be a prognostic factor for cancer patients. However, special and expensive devices are required to measure skeletal mass, and this is a major reason why skeletal mass is not used extensively for prognostic marker in clinical settings. We developed a new method to measure skeletal mass for use as a prognostic marker using CT images without special and expensive devices. In this study, we evaluated the usefulness of skeletal mass as measured by this new method as a prognostic marker for gastrointestinal cancer patients. Patients who died from gastrointestinal cancer between March 2010 and October 2013 were included. We measured the right-sided maximum psoas muscle cross sectional area (MPCA) by using CT images before surgery and after the patients developed a terminal condition. The maximum psoas muscle cross sectional area ratio (MPCA-R) was defined as follows: MPCA-R=MPCA before surgery/MPCA after developing a terminal condition. We evaluated the correlation between MPCA-R and survival. Fifty-nine patients were included. The median survival was 44 days, and MPCA-R was significantly correlated with survival (p=0.001). On receiver operating characteristic (ROC) analysis, the area under the curve (AUC) to predict 30-day and 90-day survival was 0.710 and 0.748, respectively. MPCA-R is a new and novel prognostic marker for gastrointestinal cancer patients in terminal condition.
Du, Kevin Lee; Bae, Kyounghwa; Movsas, Benjamin; Yan, Yan; Bryan, Charlene; Bruner, Deborah Watkins
2012-06-01
Previous studies by our group and others have demonstrated the importance of sociodemographic factors in cancer-related outcomes. The identification of these factors has led to novel approaches to the care of the high-risk cancer patient, specifically in the adoption of clinical interventions that convey similar benefits as favorable sociodemographic characteristics. This study examined the importance of marital status and race as prognostic indicators in men with prostate cancer. This report is a meta-analysis of 3,570 patients with prostate cancer treated in three prospective RTOG clinical trials. The Kaplan-Meier method was used to estimate the survival rate and the cumulative incidence method was used to analyze biochemical failure rate. Hazard ratios were calculated for all covariates using either the Cox or Fine and Gray's proportional hazards model or logistic regression model with associated 95% confidence intervals and p values. Hazard ratio (HR) for overall survival (OS) for single status compared to married status was 1.36 (95% CI, 1.2 to 1.53). OS HR for non-White compared to White patients was 1.05 (CI 0.92 to 1.21). In contrast, the disease-free survival (DFS) HR and biochemical failure (BF) HR were both not significantly different neither between single and married patients nor between White patients and non-White patients. Median time to death for married men was 5.68 years and for single men was 4.73 years. Median time for DFS for married men was 7.25 years and for single men was 6.56 years. Median time for BF for married men was 7.81 years and for single men was 7.05 years. Race was not associated with statistically significant differences in this analysis. Congruent with our previous work in other cancer sites, marital status predicted improved prostate cancer outcomes including overall survival. Prostate cancer is the most common visceral cancer in men in the USA. The stratification of prostate cancer risk is currently modeled solely on pathologic prognostic factors including PSA and Gleason Score. Independent of these pathologic prognostic factors, our paper describes the central sociodemographic factor of being single as a negative prognostic indicator. Single men are at high risk of poorer outcomes after prostate cancer treatment. Intriguingly, in our group of patients, race was not a significant prognostic factor. The findings in this paper add to the body of work that describes important sociodemographic prognostic factors that are currently underappreciated in patients with cancer. Future steps will include the validation of these findings in prospective studies, and the incorporation of clinical strategies that identify and compensate for sociodemographic factors that predict for poorer cancer outcomes.
Karaoğlu, Aziz; Yalcin, Suayib; Tekuzman, Gülten; Kars, Ayse; Celik, Ismail; Güler, Nilüfer; Ozişik, Yavuz; Türker, Alev; Barişta, Ibrahim; Güllü, Ibrahim
2003-01-01
We evaluated the efficacy and tolerability of weekly irinotecan as a second-line treatment in patients with colorectal cancer failing 5-fluorouracil-based chemotherapy and searched for predictive and prognostic factors. A total of 36 patients were included. Median age was 53 years (range, 33-72). One treatment cycle consisted of irinotecan, 100 mg/m2 weekly, for 4 weeks followed by a 2-week rest. Gender, age, primary site, number of metastatic sites, histologic subtype, differentiation, pretreatment CEA, CA 19-9 and lactate dehydrogenase levels and marker response to treatment were investigated as predictive factors for response to treatment and as prognostic factors in the overall survival and time to progression of the patients. A total of 120 cycles (median, 3 cycles) was delivered. An overall 14% objective response rate (1 complete and 4 partial responses) was achieved. The median response duration was 4 months (range, 2-7). Another 36% of the patients had stable disease for a median duration of 4 months (range, 2-8). Median time-to-disease progression was 4 months and overall median survival was 12 months (95% confidence interval, 9-15). Pretreatment serum CA 19-9 level and marker response to two courses of treatment were found to be clinically significant in time to progression and overall survival. Younger age (< or = 45 years) was a poor prognostic factor associated with a shorter time to progression. The major toxicity was grade 3-4 diarrhea, which occurred in 28% of the patients, and treatment was discontinued in 3 (8%) patients due to toxicity. Other hematological and non-hematological toxicities were mild and manageable. We concluded that weekly irinotecan at the dose of 100 mg/m2 is an effective and tolerable treatment option, with a 50% disease control rate, for patients with colorectal cancer failing previous 5-fluorouracil-based chemotherapy.
Prediction of Balance Compensation After Vestibular Schwannoma Surgery.
Parietti-Winkler, Cécile; Lion, Alexis; Frère, Julien; Perrin, Philippe P; Beurton, Renaud; Gauchard, Gérome C
2016-06-01
Background Balance compensation after vestibular schwannoma (VS) surgery is under the influence of specific preoperative patient and tumor characteristics. Objective To prospectively identify potential prognostic factors for balance recovery, we compared the respective influence of these preoperative characteristics on balance compensation after VS surgery. Methods In 50 patients scheduled for VS surgical ablation, we measured postural control before surgery (BS), 8 (AS8) days after, and 90 (AS90) days after surgery. Based on factors found previously in the literature, we evaluated age, body mass index and preoperative physical activity (PA), tumor grade, vestibular status, and preference for visual cues to control balance as potential prognostic factors using stepwise multiple regression models. Results An asymmetric vestibular function was the sole significant explanatory factor for impaired balance performance BS, whereas the preoperative PA alone significantly contributed to higher performance at AS8. An evaluation of patients' balance recovery over time showed that PA and vestibular status were the 2 significant predictive factors for short-term postural compensation (BS to AS8), whereas none of these preoperative factors was significantly predictive for medium-term postoperative postural recovery (AS8 to AS90). Conclusions We identified specific preoperative patient and vestibular function characteristics that may predict postoperative balance recovery after VS surgery. Better preoperative characterization of these factors in each patient could inform more personalized presurgical and postsurgical management, leading to a better, more rapid balance recovery, earlier return to normal daily activities and work, improved quality of life, and reduced medical and societal costs. © The Author(s) 2015.
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.
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
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.
The prognostic value of reactive stroma on prostate needle biopsy: a population-based study.
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.
A prognostic mutation panel for predicting cancer recurrence in stages II and III colorectal cancer.
Sho, Shonan; Court, Colin M; Winograd, Paul; Russell, Marcia M; Tomlinson, James S
2017-12-01
Approximately 20-40% of stage II/III colorectal cancer (CRC) patients develop relapse. Clinicopathological factors alone are limited in detecting these patients, resulting in potential under/over-treatment. We sought to identify a prognostic tumor mutational profile that could predict CRC recurrence. Whole-exome sequencing data were obtained for 207 patients with stage II/III CRC from The Cancer Genome Atlas. Mutational landscape in relapse-free versus relapsed cohort was compared using Fisher's exact test, followed by multivariate Cox regression to identify genes associated with cancer recurrence. Bootstrap-validation was used to examine internal/external validity. We identified five prognostic genes (APAF1, DIAPH2, NTNG1, USP7, and VAV2), which were combined to form a prognostic mutation panel. Patients with ≥1 mutation(s) within this five-gene panel had worse prognosis (3-yr relapse-free survival [RFS]: 53.0%), compared to patients with no mutation (3-yr RFS: 84.3%). In multivariate analysis, the five-gene panel remained prognostic for cancer recurrence independent of stage and high-risk features (hazard ratio 3.63, 95%CI [1.93-6.83], P < 0.0001). Furthermore, its prognostic accuracy was superior to the American Joint Commission on Cancer classification (concordance-index: 0.70 vs 0.54). Our proposed mutation panel identifies CRC patients at high-risk for recurrence, which may help guide adjuvant therapy and post-operative surveillance protocols. © 2017 Wiley Periodicals, Inc.
Nottingham Prognostic Index Plus (NPI+): a modern clinical decision making tool in breast cancer.
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.
Shimizu, Akira; Kaira, Kyoichi; Yasuda, Masahito; Asao, Takayuki; Ishikawa, Osamu
2017-01-01
Glucose-regulated protein of 78 kD (GRP78) also referred to as immunoglobulin heavy chain binding protein (BiP/GRP78) plays an important role in the endoplasmic reticulum (ER) stress. The level of BiP/GRP78 is highly elevated in various human cancers. The purpose of this study is to examine the prognostic significance of BiP/GRP78 expression in patients with malignant melanoma. A total of 133 malignant melanoma patients were analyzed, and tumor specimens were stained by immunohistochemistry for BiP/GRP78, PKR-like endoplasmic reticulum kinase (PERK), Ki-67, p53 and microvessel density (MVD) determined by CD34. BiP/GRP78 and PERK were highly expressed in 40 % (53/133) and 78 % (104/133), respectively. BiP/GRP78 disclosed a significant relationship with PERK expression, thickness, T factor, N factor, disease staging, cell proliferation (Ki-67) and MVD (CD34). By multivariate analysis, the high expression of BiP/GRP78 was identified as an independent prognostic factor for predicting poor survival against malignant melanoma. The increased BiP/GRP78 expression was clarified as an independent prognostic marker for predicting worse outcome. ER stress marker, BiP/GRP78 could be a powerful molecular target for the treatment of malignant melanoma.
Tpl-2/Cot and COX-2 in breast cancer.
Krcova, Zuzana; Ehrmann, Jiri; Krejci, Veronika; Eliopoulos, Aris; Kolar, Zdenek
2008-06-01
Breast cancer is the most common cancer in women worldwide and although mortality (129,000/year) stagnates, incidence (370,000/year) is increasing. In addition to histological type, grade, stage, hormonal and c-erbB2 status there is therefore a strong need for new and reliable prognostic and predictive factors. This minireview focuses on two potential prognostic and predictive candidates Tpl2/Cot and COX-2 and summarise information about them. Tumor progression locus 2 (Tpl2/Cot) is a serine/threonine protein kinase belonging to the family of MAP3 kinases. Activated Tpl2/Cot leads to induction of ERK1/2, JNK, NF-kappaB and p38MAPK pathways. The first study on Tpl2/Cot mRNA in breast cancer showed its increase in 40 % of cases of breast cancer but no available data exist on protein expression. Cyclo-oxygenase 2 (COX-2) is inducible by growth and inflammatory factors and contributes to the development of various tumours. Expression of COX-2 in breast cancer varied from 5-100 % in reviewed papers with significantly higher values in poorly differentiated tumours. Tpl2/Cot and COX-2 have their importance in different intracellular pathways and some of these are involved in cancer development. Briefly, the results from recent studies suggest that Tpl2/Cot and COX-2 could be prognostic factors in breast cancer.
Anisotropy of Solid Breast Lesions in 2D Shear Wave Elastography is an Indicator of Malignancy.
Skerl, Katrin; Vinnicombe, Sarah; Thomson, Kim; McLean, Denis; Giannotti, Elisabetta; Evans, Andrew
2016-01-01
To investigate if anisotropy at two-dimensional shear wave elastography (SWE) suggests malignancy and whether it correlates with prognostic and predictive factors in breast cancer. Study group A of 244 solid breast lesions was imaged with SWE between April 2013 and May 2014. Each lesion was imaged in radial and in antiradial planes, and the maximum elasticity, mean elasticity, and standard deviation were recorded and correlated with benign/malignant status, and if malignant, correlated with conventional predictive and prognostic factors. The results were compared to a study group B of 968 solid breast lesions, which were imaged in sagittal and in axial planes between 2010 and 2013. Neither benign nor malignant lesion anisotropy is plane dependent. However, malignant lesions are more anisotropic than benign lesions (P ≤ 0.001). Anisotropy correlates with increasing elasticity parameters, breast imaging-reporting and data system categories, core biopsy result, and tumor grade. Large cancers are significantly more anisotropic than small cancers (P ≤ 0.001). The optimal anisotropy cutoff threshold for benign/malignant differentiation of 150 kPa(2) achieves the best sensitivity (74%) with a reasonable specificity (63%). Anisotropy may be useful during benign/malignant differentiation of solid breast masses using SWE. Anisotropy also correlates with some prognostic factors in breast cancer. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.
Halabi, Susan; Lin, Chen-Yen; Kelly, W. Kevin; Fizazi, Karim S.; Moul, Judd W.; Kaplan, Ellen B.; Morris, Michael J.; Small, Eric J.
2014-01-01
Purpose Prognostic models for overall survival (OS) for patients with metastatic castration-resistant prostate cancer (mCRPC) are dated and do not reflect significant advances in treatment options available for these patients. This work developed and validated an updated prognostic model to predict OS in patients receiving first-line chemotherapy. Methods Data from a phase III trial of 1,050 patients with mCRPC were used (Cancer and Leukemia Group B CALGB-90401 [Alliance]). The data were randomly split into training and testing sets. A separate phase III trial served as an independent validation set. Adaptive least absolute shrinkage and selection operator selected eight factors prognostic for OS. A predictive score was computed from the regression coefficients and used to classify patients into low- and high-risk groups. The model was assessed for its predictive accuracy using the time-dependent area under the curve (tAUC). Results The model included Eastern Cooperative Oncology Group performance status, disease site, lactate dehydrogenase, opioid analgesic use, albumin, hemoglobin, prostate-specific antigen, and alkaline phosphatase. Median OS values in the high- and low-risk groups, respectively, in the testing set were 17 and 30 months (hazard ratio [HR], 2.2; P < .001); in the validation set they were 14 and 26 months (HR, 2.9; P < .001). The tAUCs were 0.73 (95% CI, 0.70 to 0.73) and 0.76 (95% CI, 0.72 to 0.76) in the testing and validation sets, respectively. Conclusion An updated prognostic model for OS in patients with mCRPC receiving first-line chemotherapy was developed and validated on an external set. This model can be used to predict OS, as well as to better select patients to participate in trials on the basis of their prognosis. PMID:24449231
Jung, Sung-Hoon; Yang, Deok-Hwan; Ahn, Jae-Sook; Kim, Yeo-Kyeoung; Kim, Hyeoung-Joon; Lee, Je-Jung
2015-01-01
We evaluated the relationship between serum lactate dehydrogenase (LDH) level with systemic inflammation score and survival in 213 patients with diffuse large B-cell lymphoma (DLBCL) receiving R-CHOP chemotherapy. The patients were classified into 3 groups based on LDH with the Glasgow Prognostic Score (L-GPS). A score of 2 was assigned to patients with elevated C-reactive protein, hypoalbuminemia and elevated LDH, a score of 1 to those with one or two abnormalities and a score of 0 to those with no abnormality. In multivariate analysis, independent poor prognostic factors for progression-free survival were L-GPS 2 [hazard ratio (HR) 5.415, p = 0.001], Eastern Cooperative Oncology Group performance status (ECOG PS) ≥2 (HR 3.504, p = 0.001) and bulky lesion (HR 2.030, p = 0.039). Independent poor prognostic factors for overall survival were L-GPS 2 (HR 5.898, p = 0.001) and ECOG PS ≥2 (HR 3.525, p = 0.001). The overall response rate for the R-CHOP chemotherapy decreased according to the L-GPS; it was 96.7% at L-GPS 0, 87% at L-GPS 1 and 75% at L-GPS 2 (p = 0.009). L-GPS based on systemic inflammatory indicators may be a useful clinical prognostic indicator for survival, and predicts the response for R-CHOP chemotherapy in patients with newly diagnosed DLBCL. © 2014 S. Karger AG, Basel.
Paik, E Sun; Sohn, Insuk; Baek, Sun-Young; Shim, Minhee; Choi, Hyun Jin; Kim, Tae-Joong; Choi, Chel Hun; Lee, Jeong-Won; Kim, Byoung-Gie; Lee, Yoo-Young; Bae, Duk-Soo
2017-01-01
Purpose This study was conducted to evaluate the prognostic significance of pre-treatment complete blood cell count (CBC), including white blood cell (WBC) differential, in epithelial ovarian cancer (EOC) patients with primary debulking surgery (PDS) and to develop nomograms for platinum sensitivity, progression-free survival (PFS), and overall survival (OS). Materials and Methods We retrospectively reviewed the records of 757 patients with EOC whose primary treatment consisted of surgical debulking and chemotherapy at Samsung Medical Center from 2002 to 2012. We subsequently created nomograms for platinum sensitivity, 3-year PFS, and 5-year OS as prediction models for prognostic variables including age, stage, grade, cancer antigen 125 level, residual disease after PDS, and pre-treatment WBC differential counts. The models were then validated by 10-fold cross-validation (CV). Results In addition to stage and residual disease after PDS, which are known predictors, lymphocyte and monocyte count were found to be significant prognostic factors for platinum-sensitivity, platelet count for PFS, and neutrophil count for OS on multivariate analysis. The area under the curves of platinum sensitivity, 3-year PFS, and 5-year OS calculated by the 10-fold CV procedure were 0.7405, 0.8159, and 0.815, respectively. Conclusion Prognostic factors including pre-treatment CBC were used to develop nomograms for platinum sensitivity, 3-year PFS, and 5-year OS of patients with EOC. These nomograms can be used to better estimate individual outcomes. PMID:27669704
Paik, E Sun; Sohn, Insuk; Baek, Sun-Young; Shim, Minhee; Choi, Hyun Jin; Kim, Tae-Joong; Choi, Chel Hun; Lee, Jeong-Won; Kim, Byoung-Gie; Lee, Yoo-Young; Bae, Duk-Soo
2017-07-01
This study was conducted to evaluate the prognostic significance of pre-treatment complete blood cell count (CBC), including white blood cell (WBC) differential, in epithelial ovarian cancer (EOC) patients with primary debulking surgery (PDS) and to develop nomograms for platinum sensitivity, progression-free survival (PFS), and overall survival (OS). We retrospectively reviewed the records of 757 patients with EOC whose primary treatment consisted of surgical debulking and chemotherapy at Samsung Medical Center from 2002 to 2012. We subsequently created nomograms for platinum sensitivity, 3-year PFS, and 5-year OS as prediction models for prognostic variables including age, stage, grade, cancer antigen 125 level, residual disease after PDS, and pre-treatment WBC differential counts. The models were then validated by 10-fold cross-validation (CV). In addition to stage and residual disease after PDS, which are known predictors, lymphocyte and monocyte count were found to be significant prognostic factors for platinum-sensitivity, platelet count for PFS, and neutrophil count for OS on multivariate analysis. The area under the curves of platinum sensitivity, 3-year PFS, and 5-year OS calculated by the 10-fold CV procedure were 0.7405, 0.8159, and 0.815, respectively. Prognostic factors including pre-treatment CBC were used to develop nomograms for platinum sensitivity, 3-year PFS, and 5-year OS of patients with EOC. These nomograms can be used to better estimate individual outcomes.
Castien, René F; van der Windt, Daniëlle A W M; Blankenstein, Annette H; Heymans, Martijn W; Dekker, Joost
2012-04-01
The aims of this study were to describe the course of chronic tension-type headache (CTTH) in participants receiving manual therapy (MT), and to develop a prognostic model for predicting recovery in participants receiving MT. Outcomes in 145 adults with CTTH who received MT as participants in a previously published randomised clinical trial (n=41) or in a prospective cohort study (n=104) were evaluated. Assessments were made at baseline and at 8 and 26 weeks of follow-up. Recovery was defined as a 50% reduction in headache days in combination with a score of 'much improved' or 'very much improved' for global perceived improvement. Potential prognostic factors were analyzed by univariable and multivariable regression analysis. After 8 weeks 78% of the participants reported recovery after MT, and after 26 weeks the frequency of recovered participants was 73%. Prognostic factors related to recovery were co-existing migraine, absence of multiple-site pain, greater cervical range of motion and higher headache intensity. In participants classified as being likely to be recovered, the posterior probability for recovery at 8 weeks was 92%, whereas for those being classified at low probability of recovery this posterior probability was 61%. It is concluded that the course of CTTH is favourable in primary care patients receiving MT. The prognostic models provide additional information to improve prediction of outcome. Copyright © 2012 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
Futamura, Naohisa; Nishida, Yoshihiro; Urakawa, Hiroshi; Kozawa, Eiji; Ikuta, Kunihiro; Hamada, Shunsuke; Ishiguro, Naoki
2014-06-01
Several studies have focused on the relationships between the expression of extracellular matrix metalloproteinase inducer (EMMPRIN) and the prognosis of patients with malignant tumors. However, few of these have investigated the expression of EMMPRIN in osteosarcoma. We examined expression levels of EMMPRIN immunohistochemically in 53 cases of high-grade osteosarcoma of the extremities and analyzed the correlation of its expression with patient prognosis. The correlation between matrix metalloproteinases (MMPs) and EMMPRIN expression and the prognostic value of co-expression were also analyzed. Staining positivity for EMMPRIN was negative in 7 cases, low in 17, moderate in 19, and strong in 10. The overall and disease-free survivals (OS and DFS) in patients with higher EMMPRIN expression (strong-moderate) were significantly lower than those in the lower (weak-negative) group (0.037 and 0.024, respectively). In multivariate analysis, age (P=0.004), location (P=0.046), and EMMPRIN expression (P=0.038) were significant prognostic factors for overall survival. EMMPRIN expression (P=0.024) was also a significant prognostic factor for disease-free survival. Co-expression analyses of EMMPRIN and MMPs revealed that strong co-expression of EMMPRIN and membrane-type 1 (MT1)-MMP had a poor prognostic value (P=0.056 for DFS, P=0.006 for OS). EMMPRIN expression and co-expression with MMPs well predict the prognosis of patients with extremity osteosarcoma, making EMMPRIN a possible therapeutic target in these patients.
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.
Dual oxidase 1: A predictive tool for the prognosis of hepatocellular carcinoma patients.
Chen, Shengsen; Ling, Qingxia; Yu, Kangkang; Huang, Chong; Li, Ning; Zheng, Jianming; Bao, Suxia; Cheng, Qi; Zhu, Mengqi; Chen, Mingquan
2016-06-01
Dual oxidase 1 (DUOX1), which is the main source of reactive oxygen species (ROS) production in the airway, can be silenced in human lung cancer and hepatocellular carcinomas. However, the prognostic value of DUOX1 expression in hepatocellular carcinoma patients is still unclear. We investigated the prognostic value of DUOX1 expression in liver cancer patients. DUOX1 mRNA expression was determined in tumor tissues and non-tumor tissues by real‑time PCR. For evaluation of the prognostic value of DUOX1 expression, Kaplan-Meier method and Cox's proportional hazards model (univariate analysis and multivariate analysis) were employed. A simple risk score was devised by using significant variables obtained from the Cox's regression analysis to further predict the HCC patient prognosis. We observed a reduced DUOX1 mRNA level in the cancer tissues in comparison to the non‑cancer tissues. More importantly, Kaplan-Meier analysis showed that patients with high DUOX1 expression had longer disease-free survival and overall survival compared with those with low expression of DUOX1. Cox's regression analysis indicated that DUOX1 expression, age, and intrahepatic metastasis may be significant prognostic factors for disease-free survival and overall survival. Finally, we found that patients with total scores of >2 and >1 were more likely to relapse and succumb to the disease than patients whose total scores were ≤2 and ≤1. In conclusion, DUOX1 expression in liver tumors is a potential prognostic tool for patients. The risk scoring system is useful for predicting the survival of liver cancer patients after tumor resection.
Molecular alterations and biomarkers in colorectal cancer
Grady, William M.; Pritchard, Colin C.
2013-01-01
The promise of precision medicine is now a clinical reality. Advances in our understanding of the molecular genetics of colorectal cancer genetics is leading to the development of a variety of biomarkers that are being used as early detection markers, prognostic markers, and markers for predicting treatment responses. This is no more evident than in the recent advances in testing colorectal cancers for specific molecular alterations in order to guide treatment with the monoclonal antibody therapies cetuximab and panitumumab, which target the epidermal growth factor receptor (EGFR). In this review, we update a prior review published in 2010 and describe our current understanding of the molecular pathogenesis of colorectal cancer and how these alterations relate to emerging biomarkers for early detection and risk stratification (diagnostic markers), prognosis (prognostic markers), and the prediction of treatment responses (predictive markers). PMID:24178577
Karel, Yasmaine H J M; Scholten-Peeters, Wendy G M; Thoomes-de Graaf, Marloes; Duijn, Edwin; Ottenheijm, Ramon P G; van den Borne, Maaike P J; Koes, Bart W; Verhagen, Arianne P; Dinant, Geert-Jan; Tetteroo, Eric; Beumer, Annechien; van Broekhoven, Joost B; Heijmans, Marcel
2013-02-11
Shoulder pain is disabling and has a considerable socio-economic impact. Over 50% of patients presenting in primary care still have symptoms after 6 months; moreover, prognostic factors such as pain intensity, age, disability level and duration of complaints are associated with poor outcome. Most shoulder complaints in this group are categorized as non-specific. Musculoskeletal ultrasound might be a useful imaging method to detect subgroups of patients with subacromial disorders.This article describes the design of a prospective cohort study evaluating the influence of known prognostic and possible prognostic factors, such as findings from musculoskeletal ultrasound outcome and working alliance, on the recovery of shoulder pain. Also, to assess the usual physiotherapy care for shoulder pain and examine the inter-rater reliability of musculoskeletal ultrasound between radiologists and physiotherapists for patients with shoulder pain. A prospective cohort study including an inter-rater reliability study. Patients presenting in primary care physiotherapy practice with shoulder pain are enrolled. At baseline validated questionnaires are used to measure patient characteristics, disease-specific characteristics and social factors. Physical examination is performed according to the expertise of the physiotherapists. Follow-up measurements will be performed 6, 12 and 26 weeks after inclusion. Primary outcome measure is perceived recovery, measured on a 7-point Likert scale. Logistic regression analysis will be used to evaluate the association between prognostic factors and recovery. The ShoCoDiP (Shoulder Complaints and using Diagnostic ultrasound in Physiotherapy practice) cohort study will provide information on current management of patients with shoulder pain in primary care, provide data to develop a prediction model for shoulder pain in primary care and to evaluate whether musculoskeletal ultrasound can improve prognosis.
Vehicle Integrated Prognostic Reasoner (VIPR) Metric Report
NASA Technical Reports Server (NTRS)
Cornhill, Dennis; Bharadwaj, Raj; Mylaraswamy, Dinkar
2013-01-01
This document outlines a set of metrics for evaluating the diagnostic and prognostic schemes developed for the Vehicle Integrated Prognostic Reasoner (VIPR), a system-level reasoner that encompasses the multiple levels of large, complex systems such as those for aircraft and spacecraft. VIPR health managers are organized hierarchically and operate together to derive diagnostic and prognostic inferences from symptoms and conditions reported by a set of diagnostic and prognostic monitors. For layered reasoners such as VIPR, the overall performance cannot be evaluated by metrics solely directed toward timely detection and accuracy of estimation of the faults in individual components. Among other factors, overall vehicle reasoner performance is governed by the effectiveness of the communication schemes between monitors and reasoners in the architecture, and the ability to propagate and fuse relevant information to make accurate, consistent, and timely predictions at different levels of the reasoner hierarchy. We outline an extended set of diagnostic and prognostics metrics that can be broadly categorized as evaluation measures for diagnostic coverage, prognostic coverage, accuracy of inferences, latency in making inferences, computational cost, and sensitivity to different fault and degradation conditions. We report metrics from Monte Carlo experiments using two variations of an aircraft reference model that supported both flat and hierarchical reasoning.
Prediction of Success in External Cephalic Version under Tocolysis: Still a Challenge.
Vaz de Macedo, Carolina; Clode, Nuno; Mendes da Graça, Luís
2015-01-01
External cephalic version is a procedure of fetal rotation to a cephalic presentation through manoeuvres applied to the maternal abdomen. There are several prognostic factors described in literature for external cephalic version success and prediction scores have been proposed, but their true implication in clinical practice is controversial. We aim to identify possible factors that could contribute to the success of an external cephalic version attempt in our population. We retrospectively examined 207 consecutive external cephalic version attempts under tocolysis conducted between January 1997 and July 2012. We consulted the department's database for the following variables: race, age, parity, maternal body mass index, gestational age, estimated fetal weight, breech category, placental location and amniotic fluid index. We performed descriptive and analytical statistics for each variable and binary logistic regression. External cephalic version was successful in 46.9% of cases (97/207). None of the included variables was associated with the outcome of external cephalic version attempts after adjustment for confounding factors. We present a success rate similar to what has been previously described in literature. However, in contrast to previous authors, we could not associate any of the analysed variables with success of the external cephalic version attempt. We believe this discrepancy is partly related to the type of statistical analysis performed. Even though there are numerous prognostic factors identified for the success in external cephalic version, care must be taken when counselling and selecting patients for this procedure. The data obtained suggests that external cephalic version should continue being offered to all eligible patients regardless of prognostic factors for success.
The biological and prognostic significance of angiotropism in uveal melanoma.
Barnhill, Raymond L; Ye, Mengliang; Batistella, Aude; Stern, Marc-Henri; Roman-Roman, Sergio; Dendale, Rémi; Lantz, Olivier; Piperno-Neumann, Sophie; Desjardins, Laurence; Cassoux, Nathalie; Lugassy, Claire
2017-02-27
Angiotropism is a marker of extravascular migration of melanoma cells along vascular and other structures and a prognostic factor in cutaneous melanoma. Because of this biological and prognostic importance in cutaneous melanoma, angiotropism was studied in uveal melanoma (UM). This retrospective study performed at a single ocular oncology referral center included 89 patients from the study period 2006-2008. All patients were diagnosed with UM from the choroid and/or ciliary body. All patients underwent enucleation for prognostic purposes and definitive therapy. Clinical, histopathological, and molecular variables included patient age, gender, extraocular extension, tumor location (ciliary body or not), optic nerve invasion, angiotropism, neurotropism, melanoma cell type, BAP1 mutation, and monosomy 3. Angiotropism was defined as melanoma cells arrayed along the abluminal vascular surfaces without intravasation in the sclera and/or episcleral tissue. The study included 51 women (57.3%) and 38 men with mean and median age: 63 years (range: 25-92). Mean follow-up was 4.4 years (range: 0.2 to 11). Fifty-three (59.6%) patients developed metastases and 48 (53.9%) were dead from metastases at last follow-up. Other principal variables recorded were angiotropism in 43.8%, extraocular extension in 7.9%, epithelioid/mixed cell type in 73.1%, BAP1 mutation in 41.3%, and monosomy 3 in 53.6% of cases. On multivariate analysis, extraocular extension, angiotropism, and monosomy 3 were predictive of metastasis, whereas tumor diameter, epithelioid cell type, angiotropism, and monosomy 3 were predictive of death. Chi-square test confirmed an association between angiotropism and metastasis and death but none with BAP1 mutation and monosomy 3. In conclusion, angiotropism and monosomy 3 were independent prognostic factors for both metastases and death in UM. However, irrespective of any prognostic value, the true importance of angiotropism is its biological significance as a marker of an alternative metastatic pathway.Laboratory Investigation advance online publication, 27 February 2017; doi:10.1038/labinvest.2017.16.
Ishimoto, Utako; Kondo, Shunsuke; Ohba, Akihiro; Sasaki, Mitsuhito; Sakamoto, Yasunari; Morizane, Chigusa; Ueno, Hideki; Okusaka, Takuji
2018-01-01
Intrahepatic cholangiocarcinoma (ICC) is a rare type of liver cancer. No clinically useful prognostic factors have been reported for patients with advanced ICC. In the present study, we aimed to evaluate the clinical prognostic factors of patients with advanced ICC receiving gemcitabine plus cisplatin combination therapy (GC) as standard first-line chemotherapy. A retrospective analysis was performed of the data of patients with ICC treated at our institution from March 2011 to January 2016. We used the Cox regression model and estimated the hazard ratios of potential prognostic factors for survival. Of 216 patients with biliary tract cancer receiving GC as first-line chemotherapy, we extracted data for 77 patients who were diagnosed with ICC and received GC as first-line chemotherapy. The median overall survival was 13.8 months (95% CI, 8.9-18.6). In multivariate analysis, pretreatment serum lactate dehydrogenase (hazard ratio [HR]: 2.53, p = 0.005), C-reactive protein (HR: 3.06, p = 0.001), and carcinoembryonic antigen (HR: 2.39, p = 0.03) levels were significantly associated with overall survival. Readily available clinical laboratory values reliably predicted the prognosis of ICC patients receiving GC therapy. If validated in other studies, these results may provide a useful tool for individual patient-risk evaluation and the design and interpretation of future trials. © 2017 S. Karger AG, Basel.
Rose, Peter G.; Java, James; Whitney, Charles W.; Stehman, Frederick B.; Lanciano, Rachelle; Thomas, Gillian M.; DiSilvestro, Paul A.
2015-01-01
Purpose To evaluate the prognostic factors in locally advanced cervical cancer limited to the pelvis and develop nomograms for 2-year progression-free survival (PFS), 5-year overall survival (OS), and pelvic recurrence. Patients and Methods We retrospectively reviewed 2,042 patients with locally advanced cervical carcinoma enrolled onto Gynecologic Oncology Group clinical trials of concurrent cisplatin-based chemotherapy and radiotherapy. Nomograms for 2-year PFS, five-year OS, and pelvic recurrence were created as visualizations of Cox proportional hazards regression models. The models were validated by bootstrap-corrected, relatively unbiased estimates of discrimination and calibration. Results Multivariable analysis identified prognostic factors including histology, race/ethnicity, performance status, tumor size, International Federation of Gynecology and Obstetrics stage, tumor grade, pelvic node status, and treatment with concurrent cisplatin-based chemotherapy. PFS, OS, and pelvic recurrence nomograms had bootstrap-corrected concordance indices of 0.62, 0.64, and 0.73, respectively, and were well calibrated. Conclusion Prognostic factors were used to develop nomograms for 2-year PFS, 5-year OS, and pelvic recurrence for locally advanced cervical cancer clinically limited to the pelvis treated with concurrent cisplatin-based chemotherapy and radiotherapy. These nomograms can be used to better estimate individual and collective outcomes. PMID:25732170
Impact of triple-negative phenotype on prognosis of patients with breast cancer brain metastases.
Xu, Zhiyuan; Schlesinger, David; Toulmin, Sushila; Rich, Tyvin; Sheehan, Jason
2012-11-01
To elucidate survival times and identify potential prognostic factors in patients with triple-negative (TN) phenotype who harbored brain metastases arising from breast cancer and who underwent stereotactic radiosurgery (SRS). A total of 103 breast cancer patients with brain metastases were treated with SRS and then studied retrospectively. Twenty-four patients (23.3%) were TN. Survival times were estimated using the Kaplan-Meier method, with a log-rank test computing the survival time difference between groups. Univariate and multivariate analyses to predict potential prognostic factors were performed using a Cox proportional hazard regression model. The presence of TN phenotype was associated with worse survival times, including overall survival after the diagnosis of primary breast cancer (43 months vs. 82 months), neurologic survival after the diagnosis of intracranial metastases, and radiosurgical survival after SRS, with median survival times being 13 months vs. 25 months and 6 months vs. 16 months, respectively (p < 0.002 in all three comparisons). On multivariate analysis, radiosurgical survival benefit was associated with non-TN status and lower recursive partitioning analysis class at the initial SRS. The TN phenotype represents a significant adverse prognostic factor with respect to overall survival, neurologic survival, and radiosurgical survival in breast cancer patients with intracranial metastasis. Recursive partitioning analysis class also served as an important and independent prognostic factor. Copyright © 2012 Elsevier Inc. All rights reserved.
Zhu, Junyong; Chen, Zuhua; Yong, Lei
2018-02-01
The majority of genes are alternatively spliced and growing evidence suggests that alternative splicing is modified in cancer and is associated with cancer progression. Systematic analysis of alternative splicing signature in ovarian cancer is lacking and greatly needed. We profiled genome-wide alternative splicing events in 408 ovarian serous cystadenocarcinoma (OV) patients in TCGA. Seven types of alternative splicing events were curated and prognostic analyses were performed with predictive models and splicing network built for OV patients. Among 48,049 mRNA splicing events in 10,582 genes, we detected 2,611 alternative splicing events in 2,036 genes which were significant associated with overall survival of OV patients. Exon skip events were the most powerful prognostic factors among the seven types. The area under the curve of the receiver-operator characteristic curve for prognostic predictor, which was built with top significant alternative splicing events, was 0.937 at 2,000 days of overall survival, indicating powerful efficiency in distinguishing patient outcome. Interestingly, splicing correlation network suggested obvious trends in the role of splicing factors in OV. In summary, we built powerful prognostic predictors for OV patients and uncovered interesting splicing networks which could be underlying mechanisms. Copyright © 2017 Elsevier Inc. All rights reserved.
Lückhoff, Hilmar K; Kruger, Frederik C; Kotze, Maritha J
2015-01-01
Heterogeneity in clinical presentation, histological severity, prognosis and therapeutic outcomes characteristic of non-alcoholic fatty liver disease (NAFLD) necessitates the development of scientifically sound classification schemes to assist clinicians in stratifying patients into meaningful prognostic subgroups. The need for replacement of invasive liver biopsies as the standard method whereby NAFLD is diagnosed, graded and staged with biomarkers of histological severity injury led to the development of composite prognostic models as potentially viable surrogate alternatives. In the present article, we review existing scoring systems used to (1) confirm the presence of undiagnosed hepatosteatosis; (2) distinguish between simple steatosis and NASH; and (3) predict advanced hepatic fibrosis, with particular emphasis on the role of NAFLD as an independent cardio-metabolic risk factor. In addition, the incorporation of functional genomic markers and application of emerging imaging technologies are discussed as a means to improve the diagnostic accuracy and predictive performance of promising composite models found to be most appropriate for widespread clinical adoption. PMID:26019735
Yang, Yu-Shang; Hu, Wei-Peng; Ni, Peng-Zhi; Wang, Wen-Ping; Yuan, Yong; Chen, Long-Qi
2017-01-01
Background Predictive value of preoperative endoscopic characteristic of esophageal tumor has not been fully evaluated. The aim of this study is to investigate the impact of esophageal luminal stenosis on survival for patients with resectable esophageal squamous cell carcinoma (ESCC). Methods The clinicopathologic characteristics of 623 ESCC patients who underwent curative resection as the primary treatment between January 2005 and April 2009 were retrospectively reviewed. The esophageal luminal stenosis measured by endoscopy was defined as a uniform measurement preoperatively. The impact of esophageal luminal stenosis on patients’ overall survival (OS) and relation with other clinicopathological features were assessed. A Cox regression model was used to identify prognostic factors. Results The results showed that OS significantly decreased in patients with manifest stenotic tumor compared with patients without luminal obstruction (P<0.05). Considerable esophageal luminal stenosis was associated with a higher T stage, longer tumor length, and poorer differentiation (all P<0.05). In multivariate survival analysis, esophageal luminal stenosis remained as an independent prognostic factor for OS (P= 0.036). Conclusions Esophageal luminal stenosis could have a significant impact on the OS in patients with resected ESCC and may provide additional prognostic value to the current staging system before any cancer-specific treatment. PMID:28118615
Panken, Guus; Verhagen, Arianne P; Terwee, Caroline B; Heymans, Martijn W
2017-08-01
Study Design Systematic review and validation study. Background Many prognostic models of knee pain outcomes have been developed for use in primary care. Variability among published studies with regard to patient population, outcome measures, and relevant prognostic factors hampers the generalizability and implementation of these models. Objectives To summarize existing prognostic models in patients with knee pain in a primary care setting and to develop and internally validate new summary prognostic models. Methods After a sensitive search strategy, 2 reviewers independently selected prognostic models for patients with nontraumatic knee pain and assessed the methodological quality of the included studies. All predictors of the included studies were evaluated, summarized, and classified. The predictors assessed in multiple studies of sufficient quality are presented in this review. Using data from the Musculoskeletal System Study (BAS) cohort of patients with a new episode of knee pain, recruited consecutively by Dutch general medical practitioners (n = 372), we used predictors with a strong level of evidence to develop new prognostic models for each outcome measure and internally validated these models. Results Sixteen studies were eligible for inclusion. We considered 11 studies to be of sufficient quality. None of these studies validated their models. Five predictors with strong evidence were related to function and 6 to recovery, and were used to compose 2 prognostic models for patients with knee pain at 1 year. Running these new models in another data set showed explained variances (R 2 ) of 0.36 (function) and 0.33 (recovery). The area under the curve of the recovery model was 0.79. After internal validation, the adjusted R 2 values of the models were 0.30 (function) and 0.20 (recovery), and the area under the curve was 0.73. Conclusion We developed 2 valid prognostic models for function and recovery for patients with nontraumatic knee pain, based on predictors with strong evidence. A longer duration of complaints predicted poorer function but did not adequately predict chance of recovery. Level of Evidence Prognosis, levels 1a and 1b. J Orthop Sports Phys Ther 2017;47(8):518-529. Epub 16 Jun 2017. doi:10.2519/jospt.2017.7142.
Lee, Jae Min; Lee, Hong Sik; Hyun, Jong Jin; Choi, Hyuk Soon; Kim, Eun Sun; Keum, Bora; Seo, Yeon Seok; Jeen, Yoon Tae; Chun, Hoon Jai; Um, Soon Ho; Kim, Chang Duck
2016-07-15
To evaluate the value of systemic inflammation-based markers as prognostic factors for advanced pancreatic cancer (PC). Data from 82 patients who underwent combination chemotherapy with gemcitabine and erlotinib for PC from 2011 to 2014 were collected retrospectively. Data that included the neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio, and the C-reactive protein (CRP)-to-albumin (CRP/Alb) ratio were analyzed. Kaplan-Meier curves, and univariate and multivariate Cox proportional hazards regression analyses were used to identify the prognostic factors associated with progression-free survival (PFS) and overall survival (OS). The univariate analysis demonstrated the prognostic value of the NLR (P = 0.049) and the CRP/Alb ratio (P = 0.047) in relation to PFS, and a positive relationship between an increase in inflammation-based markers and a poor prognosis in relation to OS. The multivariate analysis determined that an increased NLR (hazard ratio = 2.76, 95%CI: 1.33-5.75, P = 0.007) is an independent prognostic factor for poor OS. There was no association between the PLR and the patients' prognoses in those who had received chemotherapy that comprised gemcitabine and erlotinib in combination. The Kaplan-Meier method and the log-rank test determined significantly worse outcomes in relation to PFS and OS in patients with an NLR > 5 or a CRP/Alb ratio > 5. Systemic inflammation-based markers, including increases in the NLR and the CRP/Alb ratio, may be useful for predicting PC prognoses.
Angona, Anna; Alvarez-Larrán, Alberto; Bellosillo, Beatriz; Martínez-Avilés, Luz; Garcia-Pallarols, Francesc; Longarón, Raquel; Ancochea, Àgueda; Besses, Carles
2015-03-15
Two prognostic models to predict overall survival and thrombosis-free survival have been proposed: International Prognostic Score for Essential Thrombocythemia (IPSET) and IPSET-Thrombosis, respectively, based on age, leukocytes count, history of previous thrombosis, the presence of cardiovascular risk factors and the JAK2 mutational status. The aim of the present study was to assess the clinical and biological characteristics at diagnosis and during evolution in essential thrombocythemia (ET) patients as well as the factors associated with survival and thrombosis and the usefulness of these new prognostic models. We have evaluated the clinical data and the mutation status of JAK2, MPL and calreticulin of 214 ET patients diagnosed in a single center between 1985 and 2012, classified according to classical risk stratification, IPSET and IPSET-Thrombosis. With a median follow-up of 6.9 years, overall survival was not associated with any variable by multivariate analysis. Thrombotic history and leukocytes>10×10(9)/l were associated with thrombosis-free survival (TFS). In our series, IPSET prognostic systems of survival and thrombosis did not provide more clinically relevant information regarding the classic risk of thrombosis stratification. Thrombotic history and leukocytosis>10×10(9)/l were significantly associated with lower TFS, while the prognostic IPSET-Thrombosis system did not provide more information than classical thrombotic risk assessment. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.
Giraldi, L; Leoncini, E; Pastorino, R; Wünsch-Filho, V; de Carvalho, M; Lopez, R; Cadoni, G; Arzani, D; Petrelli, L; Bosetti, C; La Vecchia, C; Garavello, W; Polesel, J; Serraino, D; Simonato, L; Canova, C; Richiardi, L; Boffetta, P; Hashibe, M; Lee, Y C A; Boccia, S
2017-01-01
Abstract Background This study evaluated whether demographics, pre-diagnosis lifestyle habits and clinical data are associated with the overall survival (OS) and head and neck cancer (HNC)-specific survival in patients with HNC. Patients and methods We conducted a pooled analysis, including 4759 HNC patients from five studies within the International Head and Neck Cancer Epidemiology (INHANCE) Consortium. Cox proportional hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) were estimated including terms reported significantly associated with the survival in the univariate analysis. Results Five-year OS was 51.4% for all HNC sites combined: 50.3% for oral cavity, 41.1% for oropharynx, 35.0% for hypopharynx and 63.9% for larynx. When we considered HNC-specific survival, 5-year survival rates were 57.4% for all HNC combined: 54.6% for oral cavity, 45.4% for oropharynx, 37.1% for hypopharynx and 72.3% for larynx. Older ages at diagnosis and advanced tumour staging were unfavourable predictors of OS and HNC-specific survival. In laryngeal cancer, low educational level was an unfavourable prognostic factor for OS (HR = 2.54, 95% CI 1.01–6.38, for high school or lower versus college graduate), and status and intensity of alcohol drinking were prognostic factors both of the OS (current drinkers HR = 1.73, 95% CI 1.16–2.58) and HNC-specific survival (current drinkers HR = 2.11, 95% CI 1.22–3.66). In oropharyngeal cancer, smoking status was an independent prognostic factors for OS. Smoking intensity (>20 cigarettes/day HR = 1.41, 95% CI 1.03–1.92) was also an independent prognostic factor for OS in patients with cancer of the oral cavity. Conclusions OS and HNC-specific survival differ among HNC sites. Pre-diagnosis cigarette smoking is a prognostic factor of the OS for patients with cancer of the oral cavity and oropharynx, whereas pre-diagnosis alcohol drinking is a prognostic factor of OS and HNC-specific survival for patients with cancer of the larynx. Low educational level is an unfavourable prognostic factor for OS in laryngeal cancer patients. PMID:28945835
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
Bartlett, Thomas E.; Jones, Allison; Goode, Ellen L.; Fridley, Brooke L.; Cunningham, Julie M.; Berns, Els M. J. J.; Wik, Elisabeth; Salvesen, Helga B.; Davidson, Ben; Trope, Claes G.; Lambrechts, Sandrina; Vergote, Ignace; Widschwendter, Martin
2015-01-01
We introduce a novel per-gene measure of intra-gene DNA methylation variability (IGV) based on the Illumina Infinium HumanMethylation450 platform, which is prognostic independently of well-known predictors of clinical outcome. Using IGV, we derive a robust gene-panel prognostic signature for ovarian cancer (OC, n = 221), which validates in two independent data sets from Mayo Clinic (n = 198) and TCGA (n = 358), with significance of p = 0.004 in both sets. The OC prognostic signature gene-panel is comprised of four gene groups, which represent distinct biological processes. We show the IGV measurements of these gene groups are most likely a reflection of a mixture of intra-tumour heterogeneity and transcription factor (TF) binding/activity. IGV can be used to predict clinical outcome in patients individually, providing a surrogate read-out of hard-to-measure disease processes. PMID:26629914
Bartlett, Thomas E; Jones, Allison; Goode, Ellen L; Fridley, Brooke L; Cunningham, Julie M; Berns, Els M J J; Wik, Elisabeth; Salvesen, Helga B; Davidson, Ben; Trope, Claes G; Lambrechts, Sandrina; Vergote, Ignace; Widschwendter, Martin
2015-01-01
We introduce a novel per-gene measure of intra-gene DNA methylation variability (IGV) based on the Illumina Infinium HumanMethylation450 platform, which is prognostic independently of well-known predictors of clinical outcome. Using IGV, we derive a robust gene-panel prognostic signature for ovarian cancer (OC, n = 221), which validates in two independent data sets from Mayo Clinic (n = 198) and TCGA (n = 358), with significance of p = 0.004 in both sets. The OC prognostic signature gene-panel is comprised of four gene groups, which represent distinct biological processes. We show the IGV measurements of these gene groups are most likely a reflection of a mixture of intra-tumour heterogeneity and transcription factor (TF) binding/activity. IGV can be used to predict clinical outcome in patients individually, providing a surrogate read-out of hard-to-measure disease processes.
A framework for quantifying net benefits of alternative prognostic models.
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‡
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
High serum uric acid concentration predicts poor survival in patients with breast cancer.
Yue, Cai-Feng; Feng, Pin-Ning; Yao, Zhen-Rong; Yu, Xue-Gao; Lin, Wen-Bin; Qian, Yuan-Min; Guo, Yun-Miao; Li, Lai-Sheng; Liu, Min
2017-10-01
Uric acid is a product of purine metabolism. Recently, uric acid has gained much attraction in cancer. In this study, we aim to investigate the clinicopathological and prognostic significance of serum uric acid concentration in breast cancer patients. A total of 443 female patients with histopathologically diagnosed breast cancer were included. After a mean follow-up time of 56months, survival was analysed using the Kaplan-Meier method. To further evaluate the prognostic significance of uric acid concentrations, univariate and multivariate Cox regression analyses were applied. Of the clinicopathological parameters, uric acid concentration was associated with age, body mass index, ER status and PR status. Univariate analysis identified that patients with increased uric acid concentration had a significantly inferior overall survival (HR 2.13, 95% CI 1.15-3.94, p=0.016). In multivariate analysis, we found that high uric acid concentration is an independent prognostic factor predicting death, but insufficient to predict local relapse or distant metastasis. Kaplan-Meier analysis indicated that high uric acid concentration is related to the poor overall survival (p=0.013). High uric acid concentration predicts poor survival in patients with breast cancer, and might serve as a potential marker for appropriate management of breast cancer patients. Copyright © 2017 Elsevier B.V. All rights reserved.
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
Xu, Li; Fengji, Liang; Changning, Liu; Liangcai, Zhang; Yinghui, Li; Yu, Li; Shanguang, Chen; Jianghui, Xiong
2015-01-01
Introduction Advances in high-throughput technologies have generated diverse informative molecular markers for cancer outcome prediction. Long non-coding RNA (lncRNA) and DNA methylation as new classes of promising markers are emerging as key molecules in human cancers; however, the prognostic utility of such diverse molecular data remains to be explored. Materials and Methods We proposed a computational pipeline (IDFO) to predict patient survival by identifying prognosis-related biomarkers using multi-type molecular data (mRNA, microRNA, DNA methylation, and lncRNA) from 3198 samples of five cancer types. We assessed the predictive performance of both single molecular data and integrated multi-type molecular data in patient survival stratification, and compared their relative importance in each type of cancer, respectively. Survival analysis using multivariate Cox regression was performed to investigate the impact of the IDFO-identified markers and traditional variables on clinical outcome. Results Using the IDFO approach, we obtained good predictive performance of the molecular datasets (bootstrap accuracy: 0.71–0.97) in five cancer types. Impressively, lncRNA was identified as the best prognostic predictor in the validated cohorts of four cancer types, followed by DNA methylation, mRNA, and then microRNA. We found the incorporating of multi-type molecular data showed similar predictive power to single-type molecular data, but with the exception of the lncRNA + DNA methylation combinations in two cancers. Survival analysis of proportional hazard models confirmed a high robustness for lncRNA and DNA methylation as prognosis factors independent of traditional clinical variables. Conclusion Our study provides insight into systematically understanding the prognostic performance of diverse molecular data in both single and aggregate patterns, which may have specific reference to subsequent related studies. PMID:26606135
Wu, San-Gang; Peng, Fang; Zhou, Juan; Sun, Jia-Yuan; Li, Feng-Yan; Lin, Qin; Lin, Huan-Xin; Bao, Yong; He, Zhen-Yu
2015-01-01
Purpose: To assess the prognostic value of the number of negative lymph nodes (NLNs) in breast cancer patients with positive axillary lymph nodes after mastectomy and its predictive value for radiotherapy efficacy of different breast cancer subtypes (BCS). Methods: The records of 1,260 breast cancer patients with positive axillary lymph nodes who received mastectomy between January 1998 and December 2007 were reviewed. The prognostic impact and predictive value of the number of NLNs with respect to locoregional recurrence-free survival (LRFS), disease-free survival (DFS), and overall survival (OS) were analyzed. Results: The median follow-up time was 58 months, and 444 patients (35.2%) received postmastectomy radiotherapy (PMRT). Univariate and multivariate Cox survival analysis indicated the number of NLNs was an independent prognostic factor of LRFS, DFS, and OS. Patients with a higher number of NLNs had better survival. PMRT improved the LRFS of patients with ≤ 8 NLNs ( p < 0.001), while failing to improve the LRFS of patients with > 8 NLNs (p = 0.075). In patients with luminal A subtype, PMRT improved the LRFS, DFS, and OS of patients with ≤ 8 NLNs, but in patients with > 8 NLNs only the LRFS was improved. For patients with luminal B subtype, PMRT only improved the LRFS of patients with ≤ 8 NLNs. The number of NLNs had no predictive value for the efficacy with PMRT in Her2+ and triple-negative subtypes. Conclusions: The number of NLNs is a prognostic indicator in patients with node-positive breast cancer, and it can predict the efficacy of PMRT according to different BCS. PMID:25663944
Le Guellec, S; Lesluyes, T; Sarot, E; Valle, C; Filleron, T; Rochaix, P; Valentin, T; Pérot, G; Coindre, J-M; Chibon, F
2018-05-31
Prediction of metastatic outcome in sarcomas is challenging for clinical management since they are aggressive and carry a high metastatic risk. A 67-gene expression signature, the Complexity INdex in SARComas (CINSARC), has been identified as a better prognostic factor than the reference pathological grade. Since it cannot be applied easily in standard laboratory practice, we assessed its prognostic value using nanoString on formalin-fixed, paraffin-embedded (FFPE) blocks to evaluate its potential in clinical routine practice and guided therapeutic management. A code set consisting of 67 probes derived from the 67 genes of the CINSARC signature was built and named NanoCind®. To compare the performance of RNA-seq and nanoString (NanoCind®), we used expressions of various sarcomas (n=124, frozen samples) using both techniques and compared predictive values based on CINSARC risk groups and clinical annotations. We also used nanoString on FFPE blocks (n=67) and matching frozen and FFPE samples (n=45) to compare their level of agreement. Metastasis-free survival and agreement values in classification groups were evaluated. CINSARC strongly predicted metastatic outcome using nanoString on frozen samples (HR = 2.9, 95% CI 1.23-6.82) with similar risk-group classifications (86%). While more than 50% of FFPE blocks were not analyzable by RNA-seq owing to poor RNA quality, all samples were analyzable with nanoString. When similar (risk-group) classifications were measured with frozen tumors (RNA-seq) compared to FFPE blocks (84% agreement), the CINSARC signature was still a predictive factor of metastatic outcome with nanoString on FFPE samples (HR = 4.43, 95% CI 1.25-15.72). CINSARC is a material-independent prognostic signature for metastatic outcome in sarcomas and outperforms histological grade. Unlike RNA-seq, nanoString is not influenced by the poor quality of RNA extracted from FFPE blocks. The CINSARC signature can potentially be used in combination with nanoString (NanoCind®) in routine clinical practice on FFPE blocks to predict metastatic outcome.
VEGF and Ki-67 Overexpression in Predicting Poor Overall Survival in Adenoid Cystic Carcinoma.
Park, Seongyeol; Nam, Soo Jeong; Keam, Bhumsuk; Kim, Tae Min; Jeon, Yoon Kyung; Lee, Se-Hoon; Hah, J Hun; Kwon, Tack-Kyun; Kim, Dong-Wan; Sung, Myung-Whun; Heo, Dae Seog; Bang, Yung-Jue
2016-04-01
The purpose of this study was to evaluate potential prognostic factors in patients with adenoid cystic carcinoma (ACC). A total of 68 patients who underwent curative surgery and had available tissue were enrolled in this study. Their medical records and pathologic slides were reviewed and immunohistochemistry for basic fibroblast growth factor, fibroblast growth factor receptor (FGFR) 2, FGFR3, c-kit, Myb proto-oncogene protein, platelet-derived growth factor receptor beta, vascular endothelial growth factor (VEGF), and Ki-67 was performed. Univariate and multivariate analysis was performed for determination of disease-free survival (DFS) and overall survival (OS). In univariate analyses, primary site of nasal cavity and paranasal sinus (p=0.022) and Ki-67 expression of more than 7% (p=0.001) were statistically significant factors for poor DFS. Regarding OS, perineural invasion (p=0.032), high expression of VEGF (p=0.033), and high expression of Ki-67 (p=0.007) were poor prognostic factors. In multivariate analyses, primary site of nasal cavity and paranasal sinus (p=0.028) and high expression of Ki-67 (p=0.004) were independent risk factors for poor DFS, and high expression of VEGF (p=0.011) and Ki-67 (p=0.011) showed independent association with poor OS. High expression of VEGF and Ki-67 were independent poor prognostic factors for OS in ACC.
Solé, Francesc; Luño, Elisa; Sanzo, Carmen; Espinet, Blanca; Sanz, Guillermo F; Cervera, José; Calasanz, María José; Cigudosa, Juan Cruz; Millà, Fuensanta; Ribera, Josep Maria; Bureo, Encarna; Marquez, Maria Luisa; Arranz, Eva; Florensa, Lourdes
2005-09-01
The main prognostic factors in myelodysplastic syndromes (MDS) are chromosomal abnormalities, the proportion of blasts in bone marrow and number and degree of cytopenias. A consensus-defined International Prognostic Scoring System (IPSS) for predicting outcome and planning therapy in MDS has been developed, but its prognostic value in a large and independent series remains unproven. Furthermore, the intermediate-risk cytogenetic subgroup defined by the IPSS includes a miscellaneous number of different single abnormalities of uncertain prognostic significance at present. The main aim of the present study was to identify chromosomal abnormalities with a previously unrecognized good or poor prognosis in order to find new cytogenetic markers with predictive value. We report the cytogenetic findings in a series of 968 patients with primary MDS from the Spanish Cytogenetics Working Group, Grupo Cooperativo Español de Citogenética Hematológica (GCECGH). In this series of 968 MDS patients, we found various cytogenetic aberrations with a new prognostic impact. Complex karyotype, -7/7q- and i(17q) had a poor prognosis; normal karyotype, loss of Y chromosome, deletion 11q, deletion 12p and deletion 20q as single alterations had a good prognosis. Intermediate prognosis aberrations were rearrangements of 3q21q26, trisomy 8, trisomy 9, translocations of 11q and del(17p). Finally, a new group of single or double cytogenetic abnormalities, most of which are considered rare cytogenetic events and are usually included in the intermediate category of the IPSS, showed a trend to poor prognosis. This study suggests that some specific chromosomal abnormalities could be segregated from the IPSS intermediate-risk cytogenetic prognostic subgroup and included in the low risk or in the poor risk groups.
Compton, Michael T; Berez, Chantal; Walker, Elaine F
Family history of psychosis, gender, mode of onset, and age at onset are considered prognostic factors important to clinicians evaluating first-episode psychosis; yet, clinicians have little guidance as to how these four factors differentially predict early-course substance abuse, symptomatology, and functioning. We conducted a "head-to-head comparison" of these four factors regarding their associations with key clinical features at initial hospitalization. We also assessed potential interactions between gender and family history with regard to age at onset of psychosis and symptom severity. Consecutively admitted first-episode patients (n=334) were evaluated in two studies that rigorously assessed a number of early-course variables. Associations among variables of interest were examined using Pearson correlations, χ 2 tests, Student's t-tests, and 2×2 factorial analyses of variance. Substance (nicotine, alcohol, and cannabis) abuse and positive symptom severity were predicted only by male gender. Negative symptom severity and global functioning impairments were predicted by earlier age at onset of psychosis. General psychopathology symptom severity was predicted by both mode of onset and age at onset. Interaction effects were not observed with regard to gender and family history in predicting age at onset or symptom severity. The four prognostic features have differential associations with substance abuse, domains of symptom severity, and global functioning. Gender and age at onset of psychosis appear to be more predictive of clinical features at the time of initial evaluation (and thus presumably longer term outcomes) than the presence of a family history of psychosis and a more gradual mode of onset.
Wang, Hung-Ming; Cheng, Nai-Ming; Lee, Li-Yu; Fang, Yu-Hua Dean; Chang, Joseph Tung-Chieh; Tsan, Din-Li; Ng, Shu-Hang; Liao, Chun-Ta; Yang, Lan-Yan; Yen, Tzu-Chen
2016-02-01
The Ang's risk profile (based on p16, smoking and cancer stage) is a well-known prognostic factor in oropharyngeal squamous cell carcinoma (OPSCC). Whether heterogeneity in (18)F-fluorodeoxyglucose (FDG) positron emission tomographic (PET) images and epidermal growth factor receptor (EGFR) expression could provide additional information on clinical outcomes in advanced-stage OPSCC was investigated. Patients with stage III-IV OPSCC who completed primary therapy were eligible. Zone-size nonuniformity (ZSNU) extracted from pretreatment FDG PET scans was used as an index of image heterogeneity. EGFR and p16 expression were examined by immunohistochemistry. Disease-specific survival (DSS) and overall survival (OS) served as outcome measures. Kaplan-Meier estimates and Cox proportional hazards regression models were used for survival analysis. A bootstrap resampling technique was applied to investigate the stability of outcomes. Finally, a recursive partitioning analysis (RPA)-based model was constructed. A total of 113 patients were included, of which 28 were p16-positive. Multivariate analysis identified the Ang's profile, EGFR and ZSNU as independent predictors of both DSS and OS. Using RPA, the three risk factors were used to devise a prognostic scoring system that successfully predicted DSS in both p16-positive and -negative cases. The c-statistic of the prognostic index for DSS was 0.81, a value which was significantly superior to both AJCC stage (0.60) and the Ang's risk profile (0.68). In patients showing an Ang's high-risk profile (N = 77), the use of our scoring system clearly identified three distinct prognostic subgroups. It was concluded that a novel index may improve the prognostic stratification of patients with advanced-stage OPSCC. © 2015 UICC.
Prognostics for Microgrid Components
NASA Technical Reports Server (NTRS)
Saxena, Abhinav
2012-01-01
Prognostics is the science of predicting future performance and potential failures based on targeted condition monitoring. Moving away from the traditional reliability centric view, prognostics aims at detecting and quantifying the time to impending failures. This advance warning provides the opportunity to take actions that can preserve uptime, reduce cost of damage, or extend the life of the component. The talk will focus on the concepts and basics of prognostics from the viewpoint of condition-based systems health management. Differences with other techniques used in systems health management and philosophies of prognostics used in other domains will be shown. Examples relevant to micro grid systems and subsystems will be used to illustrate various types of prediction scenarios and the resources it take to set up a desired prognostic system. Specifically, the implementation results for power storage and power semiconductor components will demonstrate specific solution approaches of prognostics. The role of constituent elements of prognostics, such as model, prediction algorithms, failure threshold, run-to-failure data, requirements and specifications, and post-prognostic reasoning will be explained. A discussion on performance evaluation and performance metrics will conclude the technical discussion followed by general comments on open research problems and challenges in prognostics.
Flow-mediated dilation and cardiovascular event prediction: does nitric oxide matter?
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.
Molecular Pathways: Extracting Medical Knowledge from High Throughput Genomic Data
Goldstein, Theodore; Paull, Evan O.; Ellis, Matthew J.; Stuart, Joshua M.
2013-01-01
High-throughput genomic data that measures RNA expression, DNA copy number, mutation status and protein levels provide us with insights into the molecular pathway structure of cancer. Genomic lesions (amplifications, deletions, mutations) and epigenetic modifications disrupt biochemical cellular pathways. While the number of possible lesions is vast, different genomic alterations may result in concordant expression and pathway activities, producing common tumor subtypes that share similar phenotypic outcomes. How can these data be translated into medical knowledge that provides prognostic and predictive information? First generation mRNA expression signatures such as Genomic Health's Oncotype DX already provide prognostic information, but do not provide therapeutic guidance beyond the current standard of care – which is often inadequate in high-risk patients. Rather than building molecular signatures based on gene expression levels, evidence is growing that signatures based on higher-level quantities such as from genetic pathways may provide important prognostic and diagnostic cues. We provide examples of how activities for molecular entities can be predicted from pathway analysis and how the composite of all such activities, referred to here as the “activitome,” help connect genomic events to clinical factors in order to predict the drivers of poor outcome. PMID:23430023
Clay, Fiona J; Watson, Wendy L; Newstead, Stuart V; McClure, Roderick J
2012-01-01
BACKGROUND: Acute orthopedic trauma contributes substantially to the global burden of disease. OBJECTIVES: The present systematic review aimed to summarize the current knowledge concerning prognostic factors for the presence of persistent pain, pain severity and pain-related disability following acute orthopedic trauma involving a spectrum of pathologies to working-age adults. METHODS: The Ovid MEDLINE and EMBASE databases were searched for level II prognostic studies published between January 1996 and October 2010. Studies that were longitudinal and reported results with multivariate analyses appropriate for prognostic studies were included. Studies that addressed two specific injury types that have been the subject of previous reviews, namely, injuries to the spinal column and amputations, were excluded. RESULTS: The searches yielded 992 studies; 10 studies met the inclusion criteria and were rated for methodological quality. Seventeen factors were considered in more than one cohort. There was strong evidence supporting the association of female sex, older age, high pain intensity, preinjury anxiety or depression, and fewer years of education with persistent pain outcomes. There was moderate evidence supporting the association between postinjury depression or anxiety with persistent pain, and that injury severity was not a risk factor for ongoing pain. CONCLUSION: Many individuals experience persistent pain following acute trauma. Due to the lack of studies, the use of different constructs to measure the same factor and the methodological limitations associated with many of the studies, the present review was only able to reliably identify a limited set of factors that predicted persistent pain. Recommendations for the conduct of future methodologically rigorous studies of persistent pain are provided. PMID:22518366
Wang, Chunping; Lu, Yinying; Chen, Yan; Feng, Yongyi; An, Linjing; Wang, Xinzhen; Su, Shuhui; Bai, Wenlin; Zhou, Lin; Yang, Yongping; Xu, Dongping
2009-01-01
To determine the long-term prognosis of hepatocellular carcinoma (HCC) after argon-helium cryoablation and identify the risk factors that predict metastasis and recurrence. A total of 156 patients with hepatitis B-related HCC less than 5 cm in diameter who underwent curative cryoablation were followed up prospectively for tumor metastasis and recurrence. Immunohistochemistry was used to analyze the expression of vascular endothelial growth factor (VEGF). HBV basal core promoter (BCP) and precore mutations were detected by DNA sequence analysis. Post-treatment prognostic factors influencing survival, tumor metastasis and recurrence were assessed by univariate and multivariate analyses. The variables included the expression of VEGF in HCC tissues, clinical and pathologic characteristics of patients, and HBV features (HBV DNA level, HBV genotype, BCP mutation). The median follow-up period of the 156 patients was 37 months (range 8-48 months). The 1-, 2-, and 3-year overall survival rates were 92, 82 and 64%, respectively. The 1-, 2-, and 3-year recurrence-free survival rates were 72, 56 and 43%, respectively. Eighty-five patients (54.5%) had tumor recurrence or metastasis. The multivariate analysis showed that Child-Pugh class and the expression of VEGF in HCC tissues could be used as independent prognostic factors for overall survival. Meanwhile, the expression of VEGF in HCC tissues and HBV BCP mutations were found to be independent prognostic factors for recurrence-free survival. Strong expression of VEGF in HCC tissues and HBV BCP mutations are important risk predictors for recurrence or metastasis of HCC smaller than 5 cm in diameter.
Comparison of four staging systems of lymph node metastasis in gastric cancer.
Zhang, Ming; Zhu, Guanyu; Ma, Yan; Xue, Yingwei
2009-11-01
The classification of lymph node metastasis in patients with gastric cancer is still controversial. Our aim was to evaluate the relative merits of four staging systems of lymph node metastasis. In our study, the nodal status was classified according to the 5th edition of the tumor node metastasis (TNM) system, the Japanese Classification of Gastric Carcinoma (JCGC), the ratio of metastatic lymph nodes, and the size of the largest metastatic lymph node. Each staging system was scored as good (+2), fair (+1), or poor (0) with respect to the theoretical value (extent of the anatomical lymphatic tumor spread), convenience (simplicity), surgical applicability (extent of lymph node dissection), and prognostic value (ability to predict survival rate). In the multivariate analysis including the four staging systems and other potential prognostic factors, stepwise Cox regression revealed that the ratio of metastatic lymph nodes was the most independent prognostic factor. The TNM, ratio, and size systems were convenient because they had no consideration for the location of the tumor and lymph node. Although the JCGC system had advantages in theoretical value and surgical application, it was most optional due to the complexity of the system. Although all different staging systems are comparable, the metastatic lymph node ratio system is convenient, reproducible, and has the highest ability to predict survival.
[Prognostic and predictive molecular markers for urologic cancers].
Hartmann, A; Schlomm, T; Bertz, S; Heinzelmann, J; Hölters, S; Simon, R; Stoehr, R; Junker, K
2014-04-01
Molecular prognostic factors and genetic alterations as predictive markers for cancer-specific targeted therapies are used today in the clinic for many malignancies. In recent years, many molecular markers for urogenital cancers have also been identified. However, these markers are not clinically used yet. In prostate cancer, novel next-generation sequencing methods revealed a detailed picture of the molecular changes. There is growing evidence that a combination of classical histopathological and validated molecular markers could lead to a more precise estimation of prognosis, thus, resulting in an increasing number of patients with active surveillance as a possible treatment option. In patients with urothelial carcinoma, histopathological factors but also the proliferation of the tumor, mutations in oncogenes leading to an increasing proliferation rate and changes in genes responsible for invasion and metastasis are important. In addition, gene expression profiles which could distinguish aggressive tumors with high risk of metastasis from nonmetastasizing tumors have been recently identified. In the future, this could potentially allow better selection of patients needing systemic perioperative treatment. In renal cell carcinoma, many molecular markers that are associated with metastasis and survival have been identified. Some of these markers were also validated as independent prognostic markers. Selection of patients with primarily organ-confined tumors and increased risk of metastasis for adjuvant systemic therapy could be clinically relevant in the future.
Promising System for Selecting Healthy In Vitro–Fertilized Embryos in Cattle
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
An Overview of Randomization and Minimization Programs for Randomized Clinical Trials
Saghaei, Mahmoud
2011-01-01
Randomization is an essential component of sound clinical trials, which prevents selection biases and helps in blinding the allocations. Randomization is a process by which subsequent subjects are enrolled into trial groups only by chance, which essentially eliminates selection biases. A serious consequence of randomization is severe imbalance among the treatment groups with respect to some prognostic factors, which invalidate the trial results or necessitate complex and usually unreliable secondary analysis to eradicate the source of imbalances. Minimization on the other hand tends to allocate in such a way as to minimize the differences among groups, with respect to prognostic factors. Pure minimization is therefore completely deterministic, that is, one can predict the allocation of the next subject by knowing the factor levels of a previously enrolled subject and having the properties of the next subject. To eliminate the predictability of randomization, it is necessary to include some elements of randomness in the minimization algorithms. In this article brief descriptions of randomization and minimization are presented followed by introducing selected randomization and minimization programs. PMID:22606659
Prognostic Utility of Novel Biomarkers of Cardiovascular Stress: The Framingham Heart Study
Wang, Thomas J.; Wollert, Kai C.; Larson, Martin G.; Coglianese, Erin; McCabe, Elizabeth L.; Cheng, Susan; Ho, Jennifer E.; Fradley, Michael G.; Ghorbani, Anahita; Xanthakis, Vanessa; Kempf, Tibor; Benjamin, Emelia J.; Levy, Daniel; Vasan, Ramachandran S.; Januzzi, James L.
2013-01-01
Background Biomarkers for predicting cardiovascular events in community-based populations have not consistently added information to standard risk factors. A limitation of many previously studied biomarkers is their lack of cardiovascular specificity. Methods and Results To determine the prognostic value of 3 novel biomarkers induced by cardiovascular stress, we measured soluble ST2, growth differentiation factor-15, and high-sensitivity troponin I in 3,428 participants (mean age 59, 53% women) in the Framingham Heart Study. We performed multivariable-adjusted proportional hazards models to assess the individual and combined ability of the biomarkers to predict adverse outcomes. We also constructed a “multimarker” score composed of the 3 biomarkers, in addition to B-type natriuretic peptide and high-sensitivity C-reactive protein. During a mean follow-up of 11.3 years, there were 488 deaths, 336 major cardiovascular events, 162 heart failure events, and 142 coronary events. In multivariable-adjusted models, the 3 new biomarkers were associated with each endpoint (p<0.001) except for coronary events. Individuals with multimarker scores in the highest quartile had a 3-fold risk of death (adjusted hazard ratio, 3.2, 95% CI, 2.2–4.7; p<0.001), 6-fold risk of heart failure (6.2, 95% CI, 2.6–14.8; p<0.001), and 2-fold risk of cardiovascular events (1.9, 95% CI, 1.3–2.7; p=0.001). Addition of the multimarker score to clinical variables led to significant increases in the c-statistic (p=0.007 or lower) and net reclassification improvement (p=0.001 or lower). Conclusions Multiple biomarkers of cardiovascular stress are detectable in ambulatory individuals, and add prognostic value to standard risk factors for predicting death, overall cardiovascular events, and heart failure. PMID:22907935
Prognostic utility of novel biomarkers of cardiovascular stress: the Framingham Heart Study.
Wang, Thomas J; Wollert, Kai C; Larson, Martin G; Coglianese, Erin; McCabe, Elizabeth L; Cheng, Susan; Ho, Jennifer E; Fradley, Michael G; Ghorbani, Anahita; Xanthakis, Vanessa; Kempf, Tibor; Benjamin, Emelia J; Levy, Daniel; Vasan, Ramachandran S; Januzzi, James L
2012-09-25
Biomarkers for predicting cardiovascular events in community-based populations have not consistently added information to standard risk factors. A limitation of many previously studied biomarkers is their lack of cardiovascular specificity. To determine the prognostic value of 3 novel biomarkers induced by cardiovascular stress, we measured soluble ST2, growth differentiation factor-15, and high-sensitivity troponin I in 3428 participants (mean age, 59 years; 53% women) in the Framingham Heart Study. We performed multivariable-adjusted proportional hazards models to assess the individual and combined ability of the biomarkers to predict adverse outcomes. We also constructed a "multimarker" score composed of the 3 biomarkers in addition to B-type natriuretic peptide and high-sensitivity C-reactive protein. During a mean follow-up of 11.3 years, there were 488 deaths, 336 major cardiovascular events, 162 heart failure events, and 142 coronary events. In multivariable-adjusted models, the 3 new biomarkers were associated with each end point (P<0.001) except coronary events. Individuals with multimarker scores in the highest quartile had a 3-fold risk of death (adjusted hazard ratio, 3.2; 95% confidence interval, 2.2-4.7; P<0.001), 6-fold risk of heart failure (6.2; 95% confidence interval, 2.6-14.8; P<0.001), and 2-fold risk of cardiovascular events (1.9; 95% confidence interval, 1.3-2.7; P=0.001). Addition of the multimarker score to clinical variables led to significant increases in the c statistic (P=0.005 or lower) and net reclassification improvement (P=0.001 or lower). Multiple biomarkers of cardiovascular stress are detectable in ambulatory individuals and add prognostic value to standard risk factors for predicting death, overall cardiovascular events, and heart failure.
Lee, Yangkyu; Lee, Hyejung; Park, Hyunjin; Kim, Jin-Won; Hwang, Jin-Hyeok; Kim, Jaihwan; Yoon, Yoo-Seok; Han, Ho-Seong; Kim, Haeryoung
2017-09-29
SMAD4/DPC4 mutations have been associated with aggressive behavior in pancreatic ductal adenocarcinomas (PDAC), and it has recently been suggested that RUNX3 expression combined with SMAD4 status may predict the metastatic potential of PDACs. We evaluated the prognostic utility of SMAD4/RUNX3 status in human PDACs by immunohistochemistry. Immunohistochemical stains were performed for SMAD4 and RUNX3 on 210 surgically resected PDACs, and the results were correlated with the clinicopathological features. Loss of SMAD4 expression was associated with poor overall survival (OS) ( p = 0.015) and progression-free survival (PFS) ( p = 0.044). Nuclear RUNX3 expression was associated with decreased OS ( p = 0.010) and PFS ( p = 0.009), and more frequent in poorly differentiated PDACs ( p = 0.037). On combining RUNX3/SMAD4 status, RUNX3-/SMAD4+ PDACs demonstrated longer OS ( p = 0.008, median time; RUNX3-/SMAD4+ 34 months, others 17 months) and PFS ( p = 0.009, median time; RUNX3-/SMAD4+ 29 months, others 8 months) compared to RUNX3+/SMAD4+ and SMAD4- groups; RUNX3-/SMAD4+ was a significant independent predictive factor for both OS [ p = 0.025, HR 1.842 (95% CI 1.079-3.143)] and PFS [ p = 0.020, HR 1.850 (95% CI 1.100-3.113)]. SMAD4-positivity with RUNX3-negativity was a significant independent predictive factor for favorable OS and PFS in PDAC. This is the first and large clinicopathological study of RUNX3/SMAD4 expression status in human PDAC. Combination immunohistochemistry for SMAD4 and RUNX3 may help identify a favorable prognostic subgroup of PDAC.
Lee, Yangkyu; Lee, Hyejung; Park, Hyunjin; Kim, Jin-Won; Hwang, Jin-Hyeok; Kim, Jaihwan; Yoon, Yoo-Seok; Han, Ho-Seong; Kim, Haeryoung
2017-01-01
Purposes SMAD4/DPC4 mutations have been associated with aggressive behavior in pancreatic ductal adenocarcinomas (PDAC), and it has recently been suggested that RUNX3 expression combined with SMAD4 status may predict the metastatic potential of PDACs. We evaluated the prognostic utility of SMAD4/RUNX3 status in human PDACs by immunohistochemistry. Materials and Methods Immunohistochemical stains were performed for SMAD4 and RUNX3 on 210 surgically resected PDACs, and the results were correlated with the clinicopathological features. Results Loss of SMAD4 expression was associated with poor overall survival (OS) (p = 0.015) and progression-free survival (PFS) (p = 0.044). Nuclear RUNX3 expression was associated with decreased OS (p = 0.010) and PFS (p = 0.009), and more frequent in poorly differentiated PDACs (p = 0.037). On combining RUNX3/SMAD4 status, RUNX3-/SMAD4+ PDACs demonstrated longer OS (p = 0.008, median time; RUNX3-/SMAD4+ 34 months, others 17 months) and PFS (p = 0.009, median time; RUNX3-/SMAD4+ 29 months, others 8 months) compared to RUNX3+/SMAD4+ and SMAD4- groups; RUNX3-/SMAD4+ was a significant independent predictive factor for both OS [p = 0.025, HR 1.842 (95% CI 1.079-3.143)] and PFS [p = 0.020, HR 1.850 (95% CI 1.100-3.113)]. Conclusions SMAD4-positivity with RUNX3-negativity was a significant independent predictive factor for favorable OS and PFS in PDAC. This is the first and large clinicopathological study of RUNX3/SMAD4 expression status in human PDAC. Combination immunohistochemistry for SMAD4 and RUNX3 may help identify a favorable prognostic subgroup of PDAC. PMID:29100342
Keung, Emily Z; Hornick, Jason L; Bertagnolli, Monica M; Baldini, Elizabeth H; Raut, Chandrajit P
2014-02-01
Although sarcoma histology is recognized as a prognostic factor, most studies of retroperitoneal sarcomas report results combining multiple histologies and are inadequately powered to identify prognostic factors specific to a particular histology. We reviewed our experience with retroperitoneal dedifferentiated liposarcoma (RP DDLPS) to identify factors predictive of outcomes. All patients with RP DDLPS treated at our institution between 1998 and 2008 were reviewed. Multivariable Cox regression analyses were performed to identify factors predictive of progression-free survival (PFS), local recurrence-free survival (LRFS), distant recurrence-free survival (DRFS), and overall survival (OS). We identified 119 patients with primary DDLPS. Median tumor size was 20.5 cm; 21% were multifocal. French Federation of Cancer Centers Sarcoma Group tumor grades were intermediate in 53% of patients and high in 28% (unknown 19%). Resections were complete (R0/R1) in 80% of patients and incomplete (R2) in 11% (unknown 9%). Tumors were removed intact in 72% of patients and fragmented in 16% (unknown 12%). Median follow-up was 74.1 months. One hundred patients (84%) experienced recurrence or progression, with 92% occurring in the retroperitoneum. Median PFS, LRFS, DRFS, and OS were 21.1, 21.5, 45.8, and 59.0 months, respectively, and were significantly worse with R2 resection. On multivariate analysis, tumor integrity (intact vs fragmented) was predictive of PFS, multifocality predicted LRFS, and extent of resection (R0/R1 vs R2), grade, and tumor integrity predicted OS. In this cohort of primary RP DDLPS, factors under surgeon control (tumor integrity, extent of resection) and reflective of tumor biology (grade, multifocality) impact patient outcomes. Copyright © 2014 American College of Surgeons. Published by Elsevier Inc. All rights reserved.
Biegstraaten, Marieke; Hughes, Derralynn A.; Mehta, Atul; Elliott, Perry M.; Oder, Daniel; Watkinson, Oliver T.; Vaz, Frédéric M.; van Kuilenburg, André B. P.; Wanner, Christoph; Hollak, Carla E. M.
2017-01-01
Despite enzyme replacement therapy, disease progression is observed in patients with Fabry disease. Identification of factors that predict disease progression is needed to refine guidelines on initiation and cessation of enzyme replacement therapy. To study the association of potential biochemical and clinical prognostic factors with the disease course (clinical events, progression of cardiac and renal disease) we retrospectively evaluated 293 treated patients from three international centers of excellence. As expected, age, sex and phenotype were important predictors of event rate. Clinical events before enzyme replacement therapy, cardiac mass and eGFR at baseline predicted an increased event rate. eGFR was the most important predictor: hazard ratios increased from 2 at eGFR <90 ml/min/1.73m2 to 4 at eGFR <30, compared to patients with an eGFR >90. In addition, men with classical disease and a baseline eGFR <60 ml/min/1.73m2 had a faster yearly decline (-2.0 ml/min/1.73m2) than those with a baseline eGFR of >60. Proteinuria was a further independent risk factor for decline in eGFR. Increased cardiac mass at baseline was associated with the most robust decrease in cardiac mass during treatment, while presence of cardiac fibrosis predicted a stronger increase in cardiac mass (3.36 gram/m2/year). Of other cardiovascular risk factors, hypertension significantly predicted the risk for clinical events. In conclusion, besides increasing age, male sex and classical phenotype, faster disease progression while on enzyme replacement therapy is predicted by renal function, proteinuria and to a lesser extent cardiac fibrosis and hypertension. PMID:28763515
ACUTE PANCREATITIS GRAVITY PREDICTIVE FACTORS: WHICH AND WHEN TO USE THEM?
FERREIRA, Alexandre de Figueiredo; BARTELEGA, Janaina Alves; URBANO, Hugo Corrêa de Andrade; de SOUZA, Iure Kalinine Ferraz
2015-01-01
Introduction: Acute pancreatitis has as its main causes lithiasic biliary disease and alcohol abuse. Most of the time, the disease shows a self-limiting course, with a rapid recovery, only with supportive treatment. However, in a significant percentage of cases, it runs with important local and systemic complications associated with high mortality rates. Aim: To present the current state of the use of these prognostic factors (predictive scores) of gravity, as the time of application, complexity and specificity. Method: A non-systematic literature review through 28 papers, with emphasis on 13 articles published in indexed journals between 2008 and 2013 using Lilacs, Medline, Pubmed. Results: Several clinical, laboratory analysis, molecular and image variables can predict the development of severe acute pancreatitis. Some of them by themselves can be determinant to the progression of the disease to a more severe form, such as obesity, hematocrit, age and smoking. Hematocrit with a value lower than 44% and serum urea lower than 20 mg/dl, both at admission, appear as risk factors for pancreatic necrosis. But the PCR differentiates mild cases of serious ones in the first 24 h. Multifactorial scores measured on admission and during the first 48 h of hospitalization have been used in intensive care units, being the most ones used: Ranson, Apache II, Glasgow, Iget and Saps II. Conclusion: Acute pancreatitis is a disease in which several prognostic factors are employed being useful in predicting mortality and on the development of the severe form. It is suggested that the association of a multifactorial score, especially the Saps II associated with Iget, may increase the prognosis accuracy. However, the professional's preferences, the experience on the service as well as the available tools, are factors that have determined the choice of the most suitable predictive score. PMID:26537149
DOE Office of Scientific and Technical Information (OSTI.GOV)
Martin, Katherine J.; Patrick, Denis R.; Bissell, Mina J.
2008-10-20
One of the major tenets in breast cancer research is that early detection is vital for patient survival by increasing treatment options. To that end, we have previously used a novel unsupervised approach to identify a set of genes whose expression predicts prognosis of breast cancer patients. The predictive genes were selected in a well-defined three dimensional (3D) cell culture model of non-malignant human mammary epithelial cell morphogenesis as down-regulated during breast epithelial cell acinar formation and cell cycle arrest. Here we examine the ability of this gene signature (3D-signature) to predict prognosis in three independent breast cancer microarray datasetsmore » having 295, 286, and 118 samples, respectively. Our results show that the 3D-signature accurately predicts prognosis in three unrelated patient datasets. At 10 years, the probability of positive outcome was 52, 51, and 47 percent in the group with a poor-prognosis signature and 91, 75, and 71 percent in the group with a good-prognosis signature for the three datasets, respectively (Kaplan-Meier survival analysis, p<0.05). Hazard ratios for poor outcome were 5.5 (95% CI 3.0 to 12.2, p<0.0001), 2.4 (95% CI 1.6 to 3.6, p<0.0001) and 1.9 (95% CI 1.1 to 3.2, p = 0.016) and remained significant for the two larger datasets when corrected for estrogen receptor (ER) status. Hence the 3D-signature accurately predicts breast cancer outcome in both ER-positive and ER-negative tumors, though individual genes differed in their prognostic ability in the two subtypes. Genes that were prognostic in ER+ patients are AURKA, CEP55, RRM2, EPHA2, FGFBP1, and VRK1, while genes prognostic in ER patients include ACTB, FOXM1 and SERPINE2 (Kaplan-Meier p<0.05). Multivariable Cox regression analysis in the largest dataset showed that the 3D-signature was a strong independent factor in predicting breast cancer outcome. The 3D-signature accurately predicts breast cancer outcome across multiple datasets and holds prognostic value for both ER-positive and ER-negative breast cancer. The signature was selected using a novel biological approach and hence holds promise to represent the key biological processes of breast cancer.« less
Feng, Ji-Feng; Chen, Sheng; Yang, Xun
2017-09-08
We initially proposed a useful and novel prognostic model, named CCS [Combination of c-reactive protein (CRP) and squamous cell carcinoma antigen (SCC)], for predicting the postoperative survival in patients with esophageal squamous cell carcinoma (ESCC). Two hundred and fifty-two patients with resectable ESCC were included in this retrospective study. A logistic regression was performed and yielded a logistic equation. The CCS was calculated by the combined CRP and SCC. The optimal cut-off value for CCS was evaluated by X-tile program. Univariate and multivariate analyses were used to evaluate the predictive factors. In addition, a novel nomogram model was also performed to predict the prognosis for patients with ESCC. In the current study, CCS was calculated as CRP+6.33 SCC according to the logistic equation. The optimal cut-off value was 15.8 for CCS according to the X-tile program. Kaplan-Meier analyses demonstrated that high CCS group had a significantly poor 5-year cancer-specific survival (CSS) than low CCS group (10.3% vs. 47.3%, P <0.001). According to multivariate analyses, CCS ( P =0.004), but not CRP ( P =0.466) or SCC ( P =0.926), was an independent prognostic factor. A nomogram could be more accuracy for CSS (Harrell's c-index: 0.70). The CCS is a usefull and independent predictive factor in patients with ESCC.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Patel, Samir; Portelance, Lorraine; Gilbert, Lucy
2007-08-01
Purpose: To retrospectively assess prognostic factors and patterns of recurrence in patients with pathologic Stage III endometrial cancer. Methods and Materials: Between 1989 and 2003, 107 patients with pathologic International Federation of Gynecology and Obstetrics Stage III endometrial adenocarcinoma confined to the pelvis were treated at our institution. Adjuvant radiotherapy (RT) was delivered to 68 patients (64%). The influence of multiple patient- and treatment-related factors on pelvic and distant control and overall survival (OS) was evaluated. Results: Median follow-up for patients at risk was 41 months. Five-year actuarial OS was significantly improved in patients treated with adjuvant RT (68%) comparedmore » with those with resection alone (50%; p = 0.029). Age, histology, grade, uterine serosal invasion, adnexal involvement, number of extrauterine sites, and treatment with adjuvant RT predicted for improved survival in univariate analysis. Multivariate analysis revealed that grade, uterine serosal invasion, and treatment with adjuvant RT were independent predictors of survival. Five-year actuarial pelvic control was improved significantly with the delivery of adjuvant RT (74% vs. 49%; p = 0.011). Depth of myometrial invasion and treatment with adjuvant RT were independent predictors of pelvic control in multivariate analysis. Conclusions: Multiple prognostic factors predicting for the outcome of pathologic Stage III endometrial cancer patients were identified in this analysis. In particular, delivery of adjuvant RT seems to be a significant independent predictor for improved survival and pelvic control, suggesting that pelvic RT should be routinely considered in the management of these patients.« less
Sergeant, Jamie C; Parkes, Matthew J; Callaghan, Michael J
2017-01-01
Background Medical screening and load monitoring procedures are commonly used in professional football to assess factors perceived to be associated with injury. Objectives To identify prognostic factors (PFs) and models for lower extremity and spinal musculoskeletal injuries in professional/elite football players from medical screening and training load monitoring processes. Methods The MEDLINE, AMED, EMBASE, CINAHL Plus, SPORTDiscus and PubMed electronic bibliographic databases were searched (from inception to January 2017). Prospective and retrospective cohort studies of lower extremity and spinal musculoskeletal injury incidence in professional/elite football players aged between 16 and 40 years were included. The Quality in Prognostic Studies appraisal tool and the modified Grading of Recommendations Assessment, Development and Evaluation synthesis approach was used to assess the quality of the evidence. Results Fourteen studies were included. 16 specific lower extremity injury outcomes were identified. No spinal injury outcomes were identified. Meta-analysis was not possible due to heterogeneity and study quality. All evidence related to PFs and specific lower extremity injury outcomes was of very low to low quality. On the few occasions where multiple studies could be used to compare PFs and outcomes, only two factors demonstrated consensus. A history of previous hamstring injuries (HSI) and increasing age may be prognostic for future HSI in male players. Conclusions The assumed ability of medical screening tests to predict specific musculoskeletal injuries is not supported by the current evidence. Screening procedures should currently be considered as benchmarks of function or performance only. The prognostic value of load monitoring modalities is unknown. PMID:29177074
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.
Moen, Kent G; Brezova, Veronika; Skandsen, Toril; Håberg, Asta K; Folvik, Mari; Vik, Anne
2014-09-01
The aim of this study was to explore the prognostic value of visible traumatic axonal injury (TAI) loads in different MRI sequences from the early phase after adjusting for established prognostic factors. Likewise, we sought to explore the prognostic role of early apparent diffusion coefficient (ADC) values in normal-appearing corpus callosum. In this prospective study, 128 patients (mean age, 33.9 years; range, 11-69) with moderate (n = 64) and severe traumatic brain injury (TBI) were examined with MRI at a median of 8 days (range, 0-28) postinjury. TAI lesions in fluid-attenuated inversion recovery (FLAIR), diffusion-weighted imaging (DWI), and T2*-weighted gradient echo (T2*GRE) sequences were counted and FLAIR lesion volumes estimated. In patients and 47 healthy controls, mean ADC values were computed in 10 regions of interests in the normal-appearing corpus callosum. Outcome measure was the Glasgow Outcome Scale-Extended (GOS-E) at 12 months. In patients with severe TBI, number of DWI lesions and volume of FLAIR lesions in the corpus callosum, brain stem, and thalamus predicted outcome in analyses with adjustment for age, Glasgow Coma Scale score, and pupillary dilation (odds ratio, 1.3-6.9; p = <0.001-0.017). The addition of Rotterdam CT score and DWI lesions in the corpus callosum yielded the highest R2 (0.24), compared to all other MRI variables, including brain stem lesions. For patients with moderate TBI only the number of cortical contusions (p = 0.089) and Rotterdam CT score (p = 0.065) tended to predict outcome. Numbers of T2*GRE lesions did not affect outcome. Mean ADC values in the normal-appearing corpus callosum did not differ from controls. In conclusion, the loads of visible TAI lesions in the corpus callosum, brain stem, and thalamus in DWI and FLAIR were independent prognostic factors in patients with severe TBI. DWI lesions in the corpus callosum were the most important predictive MRI variable. Interestingly, number of cortical contusions in MRI and CT findings seemed more important for patients with moderate TBI.
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.
Ho, Kwok M; Honeybul, Stephen; Yip, Cheng B; Silbert, Benjamin I
2014-09-01
The authors assessed the risk factors and outcomes associated with blood-brain barrier (BBB) disruption in patients with severe, nonpenetrating, traumatic brain injury (TBI) requiring decompressive craniectomy. At 2 major neurotrauma centers in Western Australia, a retrospective cohort study was conducted among 97 adult neurotrauma patients who required an external ventricular drain (EVD) and decompressive craniectomy during 2004-2012. Glasgow Outcome Scale scores were used to assess neurological outcomes. Logistic regression was used to identify factors associated with BBB disruption, defined by a ratio of total CSF protein concentrations to total plasma protein concentration > 0.007 in the earliest CSF specimen collected after TBI. Of the 252 patients who required decompressive craniectomy, 97 (39%) required an EVD to control intracranial pressure, and biochemical evidence of BBB disruption was observed in 43 (44%). Presence of disruption was associated with more severe TBI (median predicted risk for unfavorable outcome 75% vs 63%, respectively; p = 0.001) and with worse outcomes at 6, 12, and 18 months than was absence of BBB disruption (72% vs 37% unfavorable outcomes, respectively; p = 0.015). The only risk factor significantly associated with increased risk for BBB disruption was presence of nonevacuated intracerebral hematoma (> 1 cm diameter) (OR 3.03, 95% CI 1.23-7.50; p = 0.016). Although BBB disruption was associated with more severe TBI and worse long-term outcomes, when combined with the prognostic information contained in the Corticosteroid Randomization after Significant Head Injury (CRASH) prognostic model, it did not seem to add significant prognostic value (area under the receiver operating characteristic curve 0.855 vs 0.864, respectively; p = 0.453). Biochemical evidence of BBB disruption after severe nonpenetrating TBI was common, especially among patients with large intracerebral hematomas. Disruption of the BBB was associated with more severe TBI and worse long-term outcomes, but when combined with the prognostic information contained in the CRASH prognostic model, this information did not add significant prognostic value.
McCormick, Zachary L; Reddy, Rajiv; Korn, Marc; Dayanim, David; Syed, Raafay H; Bhave, Meghan; Zhukalin, Mikhail; Choxi, Sarah; Ebrahimi, Ali; Kendall, Mark C; McCarthy, Robert J; Khan, Dost; Nagpal, Geeta; Bouffard, Karina; Walega, David R
2017-12-28
Genicular nerve radiofrequency ablation is an effective treatment for patients with chronic pain due to knee osteoarthritis; however, little is known about factors that predict procedure success. The current study evaluated the utility of genicular nerve blocks to predict the outcome of genicular nerve cooled radiofrequency ablation (cRFA) in patients with osteoarthritis. This randomized comparative trial included patients with chronic knee pain due to osteoarthritis. Participants were randomized to receive a genicular nerve block or no block prior to cRFA. Patients receiving a prognostic block that demonstrated ≥50% pain relief for six hours received cRFA. The primary outcome was the proportion of participants with ≥50% reduction in knee pain at six months. Twenty-nine participants (36 knees) had cRFA following a prognostic block, and 25 patients (35 knees) had cRFA without a block. Seventeen participants (58.6%) in the prognostic block group and 16 (64.0%) in the no block group had ≥50% pain relief at six months (P = 0.34). A 15-point decrease in the Western Ontario and McMaster Universities Osteoarthritis Index at six months was present in 17 of 29 (55.2%) in the prognostic block group and 15 of 25 (60%) in the no block group (P = 0.36). This study demonstrated clinically meaningful improvements in pain and physical function up to six months following cRFA. A prognostic genicular nerve block using a local anesthetic volume of 1 mL at each injection site and a threshold of ≥ 50% pain relief for subsequent cRFA eligibility did not improve the rate of treatment success. © 2017 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com
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.
Cai, Jun; Ma, Hong; Huang, Fang; Zhu, Dichao; Bi, Jianping; Ke, Yang; Zhang, Tao
2013-11-28
With the wide application of targeted drug therapies, the relevance of prognostic and predictive markers in patient selection has become increasingly important. Bevacizumab is commonly used in combination with chemotherapy in the treatment of metastatic colorectal cancer. However, there are currently no predictive or prognostic biomarkers for bevacizumab. Several clinical studies have evaluated bevacizumab-induced hypertension in patients with metastatic colorectal cancer. This meta-analysis was performed to better determine the association of bevacizumab-induced hypertension with outcome in patients with metastatic colorectal cancer, and to assess whether bevacizumab-induced hypertension can be used as a prognostic factor in these patients. We performed a systematic review and meta-analysis on seven published studies to investigate the relationship between hypertension and outcome of patients with metastatic colorectal cancer treated with bevacizumab. Our primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS) and overall response rate (ORR). Hazard ratios (HRs) for PFS and OS were extracted from each trial, and the log of the relative risk ratio (RR) was estimated for ORR. The occurrence of bevacizumab-induced hypertension in patients was highly associated with improvements in PFS (HR = 0.57, 95% CI: 0.46-0.72; P <0.001), OS (HR = 0.50; 95% CI: 0.37-0.68; P <0.001), and ORR (RR = 1.57, 95% CI: 1.07-2.30, P <0.05), as compared to patients without hypertension. Bevacizumab-induced hypertension may represent a prognostic factor in patients with metastatic colorectal cancer.
Okuno, Tatsuya; Wakabayashi, Masashi; Kato, Ken; Shinoda, Masayuki; Katayama, Hiroshi; Igaki, Hiroyasu; Tsubosa, Yasuhiro; Kojima, Takashi; Okabe, Hiroshi; Kimura, Yusuke; Kawano, Tatsuyuki; Kosugi, Shinichi; Toh, Yasushi; Kato, Hoichi; Nakamura, Kenichi; Fukuda, Haruhiko; Ishikura, Satoshi; Ando, Nobutoshi; Kitagawa, Yuko
2017-12-01
The aim of this study was to investigate the possible prognostic factors and predictive accuracy of the Glasgow Prognostic Score (GPS) for patients with unresectable locally advanced esophageal squamous cell carcinoma (LAESCC) treated with chemoradiotherapy. One hundred forty-two patients were enrolled in JCOG0303 and assigned to the standard cisplatin and 5-fluorouracil (PF)-radiotherapy (RT) group or the low-dose PF-RT group. One hundred thirty-one patients with sufficient data were included in this analysis. A Cox regression model was used to analyze the prognostic factors of patients with unresectable LAESCC treated with PF-RT. The GPS was classified based on the baseline C-reactive protein (CRP) and serum albumin levels. Patients with CRP ≤1.0 mg/dL and albumin ≥3.5 g/dL were classified as GPS0. If only CRP was increased or only albumin was decreased, the patients were classified as GPS1, and the patients with CRP >1.0 mg/dL and albumin <3.5 g/dL were classified as GPS2. The patients' backgrounds were as follows: median age (range), 62 (37-75); male/female, 119/12; ECOG PS 0/1/2, 64/65/2; and clinical stage (UICC 5th) IIB/III/IVA/IVB, 3/75/22/31. Multivariable analyses indicated only esophageal stenosis as a common factor for poor prognosis. In addition, overall survival tended to decrease according to the GPS subgroups (median survival time (months): GPS0/GPS1/GPS2 16.1/14.9/8.7). Esophageal stenosis was identified as a candidate stratification factor for randomized trials of unresectable LAESCC patients. Furthermore, GPS represents a prognostic factor for LAESCC patients treated with chemoradiotherapy. UMIN000000861.
Sanoff, Hanna K; Sargent, Daniel J; Campbell, Megan E; Morton, Roscoe F; Fuchs, Charles S; Ramanathan, Ramesh K; Williamson, Stephen K; Findlay, Brian P; Pitot, Henry C; Goldberg, Richard M
2008-12-10
In this report, we update survival (OS) and time-to-progression (TTP) data for the Intergroup trial N9741 after a median 5 years of follow-up by using risk-stratified and prognostic factor analyses to determine if treatment outcomes differ in specific patient subgroups. A total of 1,691 patients were randomly assigned to one of seven fluorouracil-, oxaliplatin-, and irinotecan-containing regimens. OS and TTP were calculated by treatment arm and baseline risk group (on the basis of WBC, performance status, number of sites of disease, and alkaline phosphatase). Multivariate prognostic factor analysis was used to assess clinical factors for their relationships to OS, TTP, response, and toxicity by using Cox and logistic regression models. The observed 5-year survival with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX) of 9.8% was better than with irinotecan plus bolus fluorouracil and leucovorin (IFL; 3.7%; P = .04) or with bolus irinotecan/oxaliplatin (IROX; 5.1%; P = .128). OS and TTP were significantly longer for FOLFOX (20.2 months and 8.9 months, respectively) than for IFL (14.6 months and 6.1 months, respectively; P < .001 for both) or for IROX (17.3 months and 6.7 months, respectively; P < .001 for both). OS differed by risk group: 20.7 months for low risk, 17.4 months for intermediate risk, and 9.4 months for high risk (P < .001). FOLFOX treatment was superior in all risk groups and was the most powerful prognostic factor for OS, TTP, response rate, and toxicity. The 9.8% 5-year OS in patients with metastatic colorectal cancer who were treated with first-line FOLFOX sets a new benchmark. Neither baseline risk group nor any prognostic factor examined was predictive of treatment-specific outcome. However, treatment efficacy and patient longevity varied as a function of risk group.
Sanoff, Hanna K.; Sargent, Daniel J.; Campbell, Megan E.; Morton, Roscoe F.; Fuchs, Charles S.; Ramanathan, Ramesh K.; Williamson, Stephen K.; Findlay, Brian P.; Pitot, Henry C.; Goldberg, Richard M.
2008-01-01
Purpose In this report, we update survival (OS) and time-to-progression (TTP) data for the Intergroup trial N9741 after a median 5 years of follow-up by using risk-stratified and prognostic factor analyses to determine if treatment outcomes differ in specific patient subgroups. Patients and Methods A total of 1,691 patients were randomly assigned to one of seven fluorouracil-, oxaliplatin-, and irinotecan-containing regimens. OS and TTP were calculated by treatment arm and baseline risk group (on the basis of WBC, performance status, number of sites of disease, and alkaline phosphatase). Multivariate prognostic factor analysis was used to assess clinical factors for their relationships to OS, TTP, response, and toxicity by using Cox and logistic regression models. Results The observed 5-year survival with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX) of 9.8% was better than with irinotecan plus bolus fluorouracil and leucovorin (IFL; 3.7%; P = .04) or with bolus irinotecan/oxaliplatin (IROX; 5.1%; P = .128). OS and TTP were significantly longer for FOLFOX (20.2 months and 8.9 months, respectively) than for IFL (14.6 months and 6.1 months, respectively; P < .001 for both) or for IROX (17.3 months and 6.7 months, respectively; P < .001 for both). OS differed by risk group: 20.7 months for low risk, 17.4 months for intermediate risk, and 9.4 months for high risk (P < .001). FOLFOX treatment was superior in all risk groups and was the most powerful prognostic factor for OS, TTP, response rate, and toxicity. Conclusion The 9.8% 5-year OS in patients with metastatic colorectal cancer who were treated with first-line FOLFOX sets a new benchmark. Neither baseline risk group nor any prognostic factor examined was predictive of treatment-specific outcome. However, treatment efficacy and patient longevity varied as a function of risk group. PMID:19001325
DOE Office of Scientific and Technical Information (OSTI.GOV)
Noordhuis, Maartje G.; Eijsink, Jasper J.H.; Roossink, Frank
2011-02-01
The aim of this study was to systematically review the prognostic and predictive significance of cell biological markers in cervical cancer patients primarily treated with (chemo)radiation. A PubMed, Embase, and Cochrane literature search was performed. Studies describing a relation between a cell biological marker and survival in {>=}50 cervical cancer patients primarily treated with (chemo)radiation were selected. Study quality was assessed, and studies with a quality score of 4 or lower were excluded. Cell biological markers were clustered on biological function, and the prognostic and predictive significance of these markers was described. In total, 42 studies concerning 82 cell biologicalmore » markers were included in this systematic review. In addition to cyclooxygenase-2 (COX-2) and serum squamous cell carcinoma antigen (SCC-ag) levels, markers associated with poor prognosis were involved in epidermal growth factor receptor (EGFR) signaling (EGFR and C-erbB-2) and in angiogenesis and hypoxia (carbonic anhydrase 9 and hypoxia-inducible factor-1{alpha}). Epidermal growth factor receptor and C-erbB-2 were also associated with poor response to (chemo)radiation. In conclusion, EGFR signaling is associated with poor prognosis and response to therapy in cervical cancer patients primarily treated with (chemo)radiation, whereas markers involved in angiogenesis and hypoxia, COX-2, and serum SCC-ag levels are associated with a poor prognosis. Therefore, targeting these pathways in combination with chemoradiation may improve survival in advanced-stage cervical cancer patients.« less
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.
Zier, Lucas S.; Burack, Jeffrey H.; Micco, Guy; Chipman, Anne K.; Frank, James A.; Luce, John M.; White, Douglas B.
2009-01-01
Objectives: Although discussing a prognosis is a duty of physicians caring for critically ill patients, little is known about surrogate decision-makers' beliefs about physicians' ability to prognosticate. We sought to determine: 1) surrogates' beliefs about whether physicians can accurately prognosticate for critically ill patients; and 2) how individuals use prognostic information in their role as surrogate decision-makers. Design, Setting, and Patients: Multicenter study in intensive care units of a public hospital, a tertiary care hospital, and a veterans' hospital. We conducted semistructured interviews with 50 surrogate decision-makers of critically ill patients. We analyzed the interview transcripts using grounded theory methods to inductively develop a framework to describe surrogates' beliefs about physicians' ability to prognosticate. Validation methods included triangulation by multidisciplinary analysis and member checking. Measurements and Main Results: Overall, 88% (44 of 50) of surrogates expressed doubt about physicians' ability to prognosticate for critically ill patients. Four distinct themes emerged that explained surrogates' doubts about prognostic accuracy: a belief that God could alter the course of the illness, a belief that predicting the future is inherently uncertain, prior experiences where physicians' prognostications were inaccurate, and experiences with prognostication during the patient's intensive care unit stay. Participants also identified several factors that led to belief in physicians' prognostications, such as receiving similar prognostic estimates from multiple physicians and prior experiences with accurate prognostication. Surrogates' doubts about prognostic accuracy did not prevent them from wanting prognostic information. Instead, most surrogate decision-makers view physicians' prognostications as rough estimates that are valuable in informing decisions, but are not determinative. Surrogates identified the act of prognostic disclosure as a key step in preparing emotionally and practically for the possibility that a patient may not survive. Conclusions: Although many surrogate decision-makers harbor some doubt about the accuracy of physicians' prognostications, they highly value discussions about prognosis and use the information for multiple purposes. (Crit Care Med 2008; 36: 2341–2347) PMID:18596630
Kobayashi, Takashi; Teruya, Masanori; Kishiki, Tomokazu; Kaneko, Susumu; Endo, Daisuke; Takenaka, Yoshiharu; Miki, Kenji; Kobayashi, Kaoru; Morita, Koji
2010-08-01
Few studies have investigated whether the Glasgow Prognostic Score (GPS), an inflammation-based prognostic score, is useful for postoperative prognosis of esophageal squamous cell carcinoma. GPS was calculated on the basis of admission data as follows: patients with elevated C-reactive protein level (>10 mg/l) and hypoalbuminemia (<35 g/l) were assigned to GPS2. Patients with one or no abnormal value were assigned to GPS1 or GPS0. A new scoring system was constructed using independent prognostic variables and was evaluated on whether it could be used to dictate the choice of clinical options. 65 patients with esophageal squamous cell carcinoma were enrolled. GPS and the number of lymph node metastases were found to be independent prognostic variables. The scoring system comprising GPS and the number of lymph node metastases was found to be effective in the prediction of a long-term outcome (p < 0.0001). Preoperative GPS may be useful for postoperative prognosis of patients with esophageal squamous cell carcinoma. GPS and the number of lymph node metastases could be used to identify a subgroup of patients with esophageal squamous cell carcinoma who are eligible for radical resection but show poor prognosis.
Prognosis Research Strategy (PROGRESS) 2: prognostic factor research.
Riley, Richard D; Hayden, Jill A; Steyerberg, Ewout W; Moons, Karel G M; Abrams, Keith; Kyzas, Panayiotis A; Malats, Núria; Briggs, Andrew; Schroter, Sara; Altman, Douglas G; Hemingway, Harry
2013-01-01
Prognostic factor research aims to identify factors associated with subsequent clinical outcome in people with a particular disease or health condition. In this article, the second in the PROGRESS series, the authors discuss the role of prognostic factors in current clinical practice, randomised trials, and developing new interventions, and explain why and how prognostic factor research should be improved.
olde Hartman, Tim C; Borghuis, Machteld S; Lucassen, Peter L B J; van de Laar, Floris A; Speckens, Anne E; van Weel, Chris
2009-05-01
To study the course of medically unexplained symptoms (MUS), somatisation disorder, and hypochondriasis, and related prognostic factors. Knowledge of prognostic factors in patients presenting persistent MUS might improve our understanding of the naturalistic course and the identification of patients with a high risk of a chronic course. A comprehensive search of Medline, PsycInfo, CINAHL, and EMBASE was performed to select studies focusing on patients with MUS, somatisation disorder, and hypochondriasis, and assessing prognostic factors. Studies focusing on patients with single-symptom unexplained disorder or distinctive functional somatic syndromes were excluded. A best-evidence synthesis for the interpretation of results was used. Only six studies on MUS, six studies on hypochondriasis, and one study on abridged somatisation could be included. Approximately 50% to 75% of the patients with MUS improve, whereas 10% to 30% of patients with MUS deteriorate. In patients with hypochondriasis, recovery rates vary between 30% and 50%. In studies on MUS and hypochondriasis, we found some evidence that the number of somatic symptoms at baseline influences the course of these conditions. Furthermore, the seriousness of the condition at baseline seemed to influence the prognosis. Comorbid anxiety and depression do not seem to predict the course of hypochondriasis. Due to the limited numbers of studies and their high heterogeneity, there is a lack of rigorous empirical evidence to identify relevant prognostic factors in patients presenting persistent MUS. However, it seems that a more serious condition at baseline is associated with a worse outcome.
Durand, Eric; Doutriaux, Maxime; Bettinger, Nicolas; Tron, Christophe; Fauvel, Charles; Bauer, Fabrice; Dacher, Jean-Nicolas; Bouhzam, Najime; Litzler, Pierre-Yves; Cribier, Alain; Eltchaninoff, Hélène
2017-12-11
The aim of this study was to assess the incidence, prognostic impact, and predictive factors of readmission for congestive heart failure (CHF) in patients with severe aortic stenosis treated by transcatheter aortic valve replacement (TAVR). TAVR is indicated in patients with severe symptomatic aortic stenosis in whom surgery is considered high risk or is contraindicated. Readmission for CHF after TAVR remains a challenge, and data on prognostic and predictive factors are lacking. All patients who underwent TAVR from January 2010 to December 2014 were included. Follow-up was achieved for at least 1 year and included clinical and echocardiographic data. Readmission for CHF was analyzed retrospectively. This study included 546 patients, 534 (97.8%) of whom were implanted with balloon-expandable valves preferentially via the transfemoral approach in 87.8% of cases. After 1 year, 285 patients (52.2%) had been readmitted at least once, 132 (24.1%) for CHF. Patients readmitted for CHF had an increased risk for death (p < 0.0001) and cardiac death (p < 0.0001) compared with those not readmitted for CHF. On multivariate analysis, aortic mean gradient (hazard ratio [HR]: 0.88; 95% confidence interval [CI]: 0.79 to 0.99; p = 0.03), post-procedural blood transfusion (HR: 2.27; 95% CI: 1.13 to 5.56; p = 0.009), severe post-procedural pulmonary hypertension (HR: 1.04; 95% CI: 1.00 to 1.07; p < 0.0001), and left atrial diameter (HR: 1.47; 95% CI: 1.08 to 2.01; p = 0.02) were independently associated with CHF readmission at 1 year. Readmission for CHF after TAVR was frequent and was strongly associated with 1-year mortality. Low gradient, persistent pulmonary hypertension, left atrial dilatation, and transfusions were predictive of readmission for CHF. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
Tang, Gong; Cuzick, Jack; Costantino, Joseph P; Dowsett, Mitch; Forbes, John F; Crager, Michael; Mamounas, Eleftherios P; Shak, Steven; Wolmark, Norman
2011-11-20
The 21-gene breast cancer assay recurrence score (RS) is widely used for assessing recurrence risk and predicting chemotherapy benefit in patients with estrogen receptor (ER) -positive breast cancer. Pathologic and clinical factors such as tumor size, grade, and patient age also provide independent prognostic utility. We developed a formal integration of these measures and evaluated its prognostic and predictive value. From the National Surgical Adjuvant Breast and Bowel (NSABP) B-14 and translational research cohort of the Arimidex, Tamoxifen Alone or in Combination (TransATAC) studies, we included patients who received hormonal monotherapy, had ER-positive tumors, and RS and traditional clinicopathologic factors assessed (647 and 1,088, respectively). Individual patient risk assessments from separate Cox models were combined using meta-analysis to form an RS-pathology-clinical (RSPC) assessment of distant recurrence risk. Risk assessments by RS and RSPC were compared in node-negative (N0) patients. RSPC was compared with RS for predicting chemotherapy benefit in NSABP B-20. RSPC had significantly more prognostic value for distant recurrence than did RS (P < .001) and showed better separation of risk in the study population. RSPC classified fewer patients as intermediate risk (17.8% v 26.7%, P < .001) and more patients as lower risk (63.8% v 54.2%, P < .001) than did RS among 1,444 N0 ER-positive patients. In B-20, the interaction of RSPC with chemotherapy was not statistically significant (P = .10), in contrast to the previously reported significant interaction of RS with chemotherapy (P = .037). RSPC refines the assessment of distant recurrence risk and reduces the number of patients classified as intermediate risk. Adding clinicopathologic measures did not seem to enhance the value of RS alone nor the individual biology RS identifies in predicting chemotherapy benefit.
Tang, Gong; Cuzick, Jack; Costantino, Joseph P.; Dowsett, Mitch; Forbes, John F.; Crager, Michael; Mamounas, Eleftherios P.; Shak, Steven; Wolmark, Norman
2011-01-01
Purpose The 21-gene breast cancer assay recurrence score (RS) is widely used for assessing recurrence risk and predicting chemotherapy benefit in patients with estrogen receptor (ER) –positive breast cancer. Pathologic and clinical factors such as tumor size, grade, and patient age also provide independent prognostic utility. We developed a formal integration of these measures and evaluated its prognostic and predictive value. Patients and Methods From the National Surgical Adjuvant Breast and Bowel (NSABP) B-14 and translational research cohort of the Arimidex, Tamoxifen Alone or in Combination (TransATAC) studies, we included patients who received hormonal monotherapy, had ER-positive tumors, and RS and traditional clinicopathologic factors assessed (647 and 1,088, respectively). Individual patient risk assessments from separate Cox models were combined using meta-analysis to form an RS-pathology-clinical (RSPC) assessment of distant recurrence risk. Risk assessments by RS and RSPC were compared in node-negative (N0) patients. RSPC was compared with RS for predicting chemotherapy benefit in NSABP B-20. Results RSPC had significantly more prognostic value for distant recurrence than did RS (P < .001) and showed better separation of risk in the study population. RSPC classified fewer patients as intermediate risk (17.8% v 26.7%, P < .001) and more patients as lower risk (63.8% v 54.2%, P < .001) than did RS among 1,444 N0 ER-positive patients. In B-20, the interaction of RSPC with chemotherapy was not statistically significant (P = .10), in contrast to the previously reported significant interaction of RS with chemotherapy (P = .037). Conclusion RSPC refines the assessment of distant recurrence risk and reduces the number of patients classified as intermediate risk. Adding clinicopathologic measures did not seem to enhance the value of RS alone nor the individual biology RS identifies in predicting chemotherapy benefit. PMID:22010013
Feldman, Arthur M.; Mann, Douglas L.; She, Lilin; Bristow, Michael R.; Maisel, Alan S.; McNamara, Dennis M.; Walsh, Ryan; Lee, Dorellyn L.; Wos, Stanislaw; Lang, Irene; Wells, Gretchen; Drazner, Mark H.; Schmedtje, John F.; Pauly, Daniel F.; Sueta, Carla A.; Di Maio, Michael; Kron, Irving L.; Velazquez, Eric J.; Lee, Kerry L.
2013-01-01
Background Patients with heart failure and coronary artery disease often undergo coronary artery bypass grafting (CABG) but assessment of the risk of an adverse outcome in these patients is difficult. To evaluate the ability of biomarkers to contribute independent prognostic information in these patients, we measured levels in patients enrolled in the Biomarker Sub-studies of the Surgical Treatment for Ischemic Heart Failure (STICH) trials. Patients in STICH Hypothesis 1 were randomized to medical therapy or CABG whereas those in STICH Hypothesis 2 were randomized to CABG or CABG with left ventricular reconstruction. Methods and Results In sub-study patients assigned to STICH Hypothesis 1 (n=606), plasma levels of sTNFR-1 and BNP were highly predictive of the primary outcome variable of mortality by univariate analysis (BNP χ2=40.6; p<0.0001: sTNFR-1 χ2=38,9; p<0.0001). When considered in the context of multivariable analysis, both BNP and sTNFR-1 contributed independent prognostic information beyond the information provided by a large array of clinical factors independent of treatment assignment. Consistent results were seen when assessing the predictive value of BNP and sTNFR-1 in patients assigned to STICH Hypothesis 2 (n=626). Both plasma levels of BNP (χ2=30.3) and sTNFR-1 (χ2=45.5) were highly predictive in univariate analysis (p<0.0001) as well as in multivariable analysis for the primary endpoint of death or cardiac hospitalization. In multivariable analysis, the prognostic information contributed by BNP (χ2=6.0; p=0.049) and sTNFR-1 (χ2=8.8; p=0.003) remained statistically significant even after accounting for other clinical information. Although the biomarkers added little discriminatory improvement to the clinical factors (increase in c-index ≤ 0.1), Net Reclassification Improvement (NRI) for the primary endpoints was 0.29 for BNP and 0.21 for sTNFR-1in the Hypothesis 1 cohort, and 0.15 for BNP and 0.30 for sTNFR-1 in the Hypothesis 2 cohort, reflecting important predictive improvement. Conclusions Elevated levels of sTNFR-1 and BNP are strongly associated with outcomes, independent of therapy, in two large and independent studies, thus providing important cross-validation for the prognostic importance of these two biomarkers. PMID:23584092
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.
An 8-gene qRT-PCR-based gene expression score that has prognostic value in early breast cancer
2010-01-01
Background Gene expression profiling may improve prognostic accuracy in patients with early breast cancer. Our objective was to demonstrate that it is possible to develop a simple molecular signature to predict distant relapse. Methods We included 153 patients with stage I-II hormonal receptor-positive breast cancer. RNA was isolated from formalin-fixed paraffin-embedded samples and qRT-PCR amplification of 83 genes was performed with gene expression assays. The genes we analyzed were those included in the 70-Gene Signature, the Recurrence Score and the Two-Gene Index. The association among gene expression, clinical variables and distant metastasis-free survival was analyzed using Cox regression models. Results An 8-gene prognostic score was defined. Distant metastasis-free survival at 5 years was 97% for patients defined as low-risk by the prognostic score versus 60% for patients defined as high-risk. The 8-gene score remained a significant factor in multivariate analysis and its performance was similar to that of two validated gene profiles: the 70-Gene Signature and the Recurrence Score. The validity of the signature was verified in independent cohorts obtained from the GEO database. Conclusions This study identifies a simple gene expression score that complements histopathological prognostic factors in breast cancer, and can be determined in paraffin-embedded samples. PMID:20584321
Hamilton, C A; Miller, A; Casablanca, Y; Horowitz, N S; Rungruang, B; Krivak, T C; Richard, S D; Rodriguez, N; Birrer, M J; Backes, F J; Geller, M A; Quinn, M; Goodheart, M J; Mutch, D G; Kavanagh, J J; Maxwell, G L; Bookman, M A
2018-02-01
To identify clinicopathologic factors associated with 10-year overall survival in epithelial ovarian cancer (EOC) and primary peritoneal cancer (PPC), and to develop a predictive model identifying long-term survivors. Demographic, surgical, and clinicopathologic data were abstracted from GOG 182 records. The association between clinical variables and long-term survival (LTS) (>10years) was assessed using multivariable regression analysis. Bootstrap methods were used to develop predictive models from known prognostic clinical factors and predictive accuracy was quantified using optimism-adjusted area under the receiver operating characteristic curve (AUC). The analysis dataset included 3010 evaluable patients, of whom 195 survived greater than ten years. These patients were more likely to have better performance status, endometrioid histology, stage III (rather than stage IV) disease, absence of ascites, less extensive preoperative disease distribution, microscopic disease residual following cyoreduction (R0), and decreased complexity of surgery (p<0.01). Multivariable regression analysis revealed that lower CA-125 levels, absence of ascites, stage, and R0 were significant independent predictors of LTS. A predictive model created using these variables had an AUC=0.729, which outperformed any of the individual predictors. The absence of ascites, a low CA-125, stage, and R0 at the time of cytoreduction are factors associated with LTS when controlling for other confounders. An extensively annotated clinicopathologic prediction model for LTS fell short of clinical utility suggesting that prognostic molecular profiles are needed to better predict which patients are likely to be long-term survivors. Published by Elsevier Inc.
Hamilton, C. A.; Miller, A.; Casablanca, Y.; Horowitz, N. S.; Rungruang, B.; Krivak, T. C.; Richard, S. D.; Rodriguez, N.; Birrer, M.J.; Backes, F.J.; Geller, M.A.; Quinn, M.; Goodheart, M.J.; Mutch, D.G.; Kavanagh, J.J.; Maxwell, G. L.; Bookman, M. A.
2018-01-01
Objective To identify clinicopathologic factors associated with 10-year overall survival in epithelial ovarian cancer (EOC) and primary peritoneal cancer (PPC), and to develop a predictive model identifying long-term survivors. Methods Demographic, surgical, and clinicopathologic data were abstracted from GOG 182 records. The association between clinical variables and long-term survival (LTS) (>10 years) was assessed using multivariable regression analysis. Bootstrap methods were used to develop predictive models from known prognostic clinical factors and predictive accuracy was quantified using optimism-adjusted area under the receiver operating characteristic curve (AUC). Results The analysis dataset included 3,010 evaluable patients, of whom 195 survived greater than ten years. These patients were more likely to have better performance status, endometrioid histology, stage III (rather than stage IV) disease, absence of ascites, less extensive preoperative disease distribution, microscopic disease residual following cyoreduction (R0), and decreased complexity of surgery (p<0.01). Multivariable regression analysis revealed that lower CA-125 levels, absence of ascites, stage, and R0 were significant independent predictors of LTS. A predictive model created using these variables had an AUC=0.729, which outperformed any of the individual predictors. Conclusions The absence of ascites, a low CA-125, stage, and R0 at the time of cytoreduction are factors associated with LTS when controlling for other confounders. An extensively annotated clinicopathologic prediction model for LTS fell short of clinical utility suggesting that prognostic molecular profiles are needed to better predict which patients are likely to be long-term survivors. PMID:29195926
Dantan, Etienne; Combescure, Christophe; Lorent, Marine; Ashton-Chess, Joanna; Daguin, Pascal; Classe, Jean-Marc; Giral, Magali; Foucher, Yohann
2014-04-01
Predicting chronic disease evolution from a prognostic marker is a key field of research in clinical epidemiology. However, the prognostic capacity of a marker is not systematically evaluated using the appropriate methodology. We proposed the use of simple equations to calculate time-dependent sensitivity and specificity based on published survival curves and other time-dependent indicators as predictive values, likelihood ratios, and posttest probability ratios to reappraise prognostic marker accuracy. The methodology is illustrated by back calculating time-dependent indicators from published articles presenting a marker as highly correlated with the time to event, concluding on the high prognostic capacity of the marker, and presenting the Kaplan-Meier survival curves. The tools necessary to run these direct and simple computations are available online at http://www.divat.fr/en/online-calculators/evalbiom. Our examples illustrate that published conclusions about prognostic marker accuracy may be overoptimistic, thus giving potential for major mistakes in therapeutic decisions. Our approach should help readers better evaluate clinical articles reporting on prognostic markers. Time-dependent sensitivity and specificity inform on the inherent prognostic capacity of a marker for a defined prognostic time. Time-dependent predictive values, likelihood ratios, and posttest probability ratios may additionally contribute to interpret the marker's prognostic capacity. Copyright © 2014 Elsevier Inc. All rights reserved.
Ensor, Joie; Riley, Richard D; Jowett, Sue; Monahan, Mark; Snell, Kym Ie; Bayliss, Susan; Moore, David; Fitzmaurice, David
2016-02-01
Unprovoked first venous thromboembolism (VTE) is defined as VTE in the absence of a temporary provoking factor such as surgery, immobility and other temporary factors. Recurrent VTE in unprovoked patients is highly prevalent, but easily preventable with oral anticoagulant (OAC) therapy. The unprovoked population is highly heterogeneous in terms of risk of recurrent VTE. The first aim of the project is to review existing prognostic models which stratify individuals by their recurrence risk, therefore potentially allowing tailored treatment strategies. The second aim is to enhance the existing research in this field, by developing and externally validating a new prognostic model for individual risk prediction, using a pooled database containing individual patient data (IPD) from several studies. The final aim is to assess the economic cost-effectiveness of the proposed prognostic model if it is used as a decision rule for resuming OAC therapy, compared with current standard treatment strategies. Standard systematic review methodology was used to identify relevant prognostic model development, validation and cost-effectiveness studies. Bibliographic databases (including MEDLINE, EMBASE and The Cochrane Library) were searched using terms relating to the clinical area and prognosis. Reviewing was undertaken by two reviewers independently using pre-defined criteria. Included full-text articles were data extracted and quality assessed. Critical appraisal of included full texts was undertaken and comparisons made of model performance. A prognostic model was developed using IPD from the pooled database of seven trials. A novel internal-external cross-validation (IECV) approach was used to develop and validate a prognostic model, with external validation undertaken in each of the trials iteratively. Given good performance in the IECV approach, a final model was developed using all trials data. A Markov patient-level simulation was used to consider the economic cost-effectiveness of using a decision rule (based on the prognostic model) to decide on resumption of OAC therapy (or not). Three full-text articles were identified by the systematic review. Critical appraisal identified methodological and applicability issues; in particular, all three existing models did not have external validation. To address this, new prognostic models were sought with external validation. Two potential models were considered: one for use at cessation of therapy (pre D-dimer), and one for use after cessation of therapy (post D-dimer). Model performance measured in the external validation trials showed strong calibration performance for both models. The post D-dimer model performed substantially better in terms of discrimination (c = 0.69), better separating high- and low-risk patients. The economic evaluation identified that a decision rule based on the final post D-dimer model may be cost-effective for patients with predicted risk of recurrence of over 8% annually; this suggests continued therapy for patients with predicted risks ≥ 8% and cessation of therapy otherwise. The post D-dimer model performed strongly and could be useful to predict individuals' risk of recurrence at any time up to 2-3 years, thereby aiding patient counselling and treatment decisions. A decision rule using this model may be cost-effective for informing clinical judgement and patient opinion in treatment decisions. Further research may investigate new predictors to enhance model performance and aim to further externally validate to confirm performance in new, non-trial populations. Finally, it is essential that further research is conducted to develop a model predicting bleeding risk on therapy, to manage the balance between the risks of recurrence and bleeding. This study is registered as PROSPERO CRD42013003494. The National Institute for Health Research Health Technology Assessment programme.
Guinney, Justin; Wang, Tao; Laajala, Teemu D; Winner, Kimberly Kanigel; Bare, J Christopher; Neto, Elias Chaibub; Khan, Suleiman A; Peddinti, Gopal; Airola, Antti; Pahikkala, Tapio; Mirtti, Tuomas; Yu, Thomas; Bot, Brian M; Shen, Liji; Abdallah, Kald; Norman, Thea; Friend, Stephen; Stolovitzky, Gustavo; Soule, Howard; Sweeney, Christopher J; Ryan, Charles J; Scher, Howard I; Sartor, Oliver; Xie, Yang; Aittokallio, Tero; Zhou, Fang Liz; Costello, James C
2016-01-01
Summary Background Improvements to prognostic models in metastatic castration-resistant prostate cancer have the potential to augment clinical trial design and guide treatment strategies. In partnership with Project Data Sphere, a not-for-profit initiative allowing data from cancer clinical trials to be shared broadly with researchers, we designed an open-data, crowdsourced, DREAM (Dialogue for Reverse Engineering Assessments and Methods) challenge to not only identify a better prognostic model for prediction of survival in patients with metastatic castration-resistant prostate cancer but also engage a community of international data scientists to study this disease. Methods Data from the comparator arms of four phase 3 clinical trials in first-line metastatic castration-resistant prostate cancer were obtained from Project Data Sphere, comprising 476 patients treated with docetaxel and prednisone from the ASCENT2 trial, 526 patients treated with docetaxel, prednisone, and placebo in the MAINSAIL trial, 598 patients treated with docetaxel, prednisone or prednisolone, and placebo in the VENICE trial, and 470 patients treated with docetaxel and placebo in the ENTHUSE 33 trial. Datasets consisting of more than 150 clinical variables were curated centrally, including demographics, laboratory values, medical history, lesion sites, and previous treatments. Data from ASCENT2, MAINSAIL, and VENICE were released publicly to be used as training data to predict the outcome of interest—namely, overall survival. Clinical data were also released for ENTHUSE 33, but data for outcome variables (overall survival and event status) were hidden from the challenge participants so that ENTHUSE 33 could be used for independent validation. Methods were evaluated using the integrated time-dependent area under the curve (iAUC). The reference model, based on eight clinical variables and a penalised Cox proportional-hazards model, was used to compare method performance. Further validation was done using data from a fifth trial—ENTHUSE M1—in which 266 patients with metastatic castration-resistant prostate cancer were treated with placebo alone. Findings 50 independent methods were developed to predict overall survival and were evaluated through the DREAM challenge. The top performer was based on an ensemble of penalised Cox regression models (ePCR), which uniquely identified predictive interaction effects with immune biomarkers and markers of hepatic and renal function. Overall, ePCR outperformed all other methods (iAUC 0·791; Bayes factor >5) and surpassed the reference model (iAUC 0·743; Bayes factor >20). Both the ePCR model and reference models stratified patients in the ENTHUSE 33 trial into high-risk and low-risk groups with significantly different overall survival (ePCR: hazard ratio 3·32, 95% CI 2·39–4·62, p<0·0001; reference model: 2·56, 1·85–3·53, p<0·0001). The new model was validated further on the ENTHUSE M1 cohort with similarly high performance (iAUC 0·768). Meta-analysis across all methods confirmed previously identified predictive clinical variables and revealed aspartate aminotransferase as an important, albeit previously under-reported, prognostic biomarker. Interpretation Novel prognostic factors were delineated, and the assessment of 50 methods developed by independent international teams establishes a benchmark for development of methods in the future. The results of this effort show that data-sharing, when combined with a crowdsourced challenge, is a robust and powerful framework to develop new prognostic models in advanced prostate cancer. Funding Sanofi US Services, Project Data Sphere. PMID:27864015
Guinney, Justin; Wang, Tao; Laajala, Teemu D; Winner, Kimberly Kanigel; Bare, J Christopher; Neto, Elias Chaibub; Khan, Suleiman A; Peddinti, Gopal; Airola, Antti; Pahikkala, Tapio; Mirtti, Tuomas; Yu, Thomas; Bot, Brian M; Shen, Liji; Abdallah, Kald; Norman, Thea; Friend, Stephen; Stolovitzky, Gustavo; Soule, Howard; Sweeney, Christopher J; Ryan, Charles J; Scher, Howard I; Sartor, Oliver; Xie, Yang; Aittokallio, Tero; Zhou, Fang Liz; Costello, James C
2017-01-01
Improvements to prognostic models in metastatic castration-resistant prostate cancer have the potential to augment clinical trial design and guide treatment strategies. In partnership with Project Data Sphere, a not-for-profit initiative allowing data from cancer clinical trials to be shared broadly with researchers, we designed an open-data, crowdsourced, DREAM (Dialogue for Reverse Engineering Assessments and Methods) challenge to not only identify a better prognostic model for prediction of survival in patients with metastatic castration-resistant prostate cancer but also engage a community of international data scientists to study this disease. Data from the comparator arms of four phase 3 clinical trials in first-line metastatic castration-resistant prostate cancer were obtained from Project Data Sphere, comprising 476 patients treated with docetaxel and prednisone from the ASCENT2 trial, 526 patients treated with docetaxel, prednisone, and placebo in the MAINSAIL trial, 598 patients treated with docetaxel, prednisone or prednisolone, and placebo in the VENICE trial, and 470 patients treated with docetaxel and placebo in the ENTHUSE 33 trial. Datasets consisting of more than 150 clinical variables were curated centrally, including demographics, laboratory values, medical history, lesion sites, and previous treatments. Data from ASCENT2, MAINSAIL, and VENICE were released publicly to be used as training data to predict the outcome of interest-namely, overall survival. Clinical data were also released for ENTHUSE 33, but data for outcome variables (overall survival and event status) were hidden from the challenge participants so that ENTHUSE 33 could be used for independent validation. Methods were evaluated using the integrated time-dependent area under the curve (iAUC). The reference model, based on eight clinical variables and a penalised Cox proportional-hazards model, was used to compare method performance. Further validation was done using data from a fifth trial-ENTHUSE M1-in which 266 patients with metastatic castration-resistant prostate cancer were treated with placebo alone. 50 independent methods were developed to predict overall survival and were evaluated through the DREAM challenge. The top performer was based on an ensemble of penalised Cox regression models (ePCR), which uniquely identified predictive interaction effects with immune biomarkers and markers of hepatic and renal function. Overall, ePCR outperformed all other methods (iAUC 0·791; Bayes factor >5) and surpassed the reference model (iAUC 0·743; Bayes factor >20). Both the ePCR model and reference models stratified patients in the ENTHUSE 33 trial into high-risk and low-risk groups with significantly different overall survival (ePCR: hazard ratio 3·32, 95% CI 2·39-4·62, p<0·0001; reference model: 2·56, 1·85-3·53, p<0·0001). The new model was validated further on the ENTHUSE M1 cohort with similarly high performance (iAUC 0·768). Meta-analysis across all methods confirmed previously identified predictive clinical variables and revealed aspartate aminotransferase as an important, albeit previously under-reported, prognostic biomarker. Novel prognostic factors were delineated, and the assessment of 50 methods developed by independent international teams establishes a benchmark for development of methods in the future. The results of this effort show that data-sharing, when combined with a crowdsourced challenge, is a robust and powerful framework to develop new prognostic models in advanced prostate cancer. Sanofi US Services, Project Data Sphere. Copyright © 2017 Elsevier Ltd. All rights reserved.
A Novel Independent Survival Predictor in Pulmonary Embolism: Prognostic Nutritional Index.
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.
Lo, Benjamin W. Y.; Macdonald, R. Loch; Baker, Andrew; Levine, Mitchell A. H.
2013-01-01
Objective. The novel clinical prediction approach of Bayesian neural networks with fuzzy logic inferences is created and applied to derive prognostic decision rules in cerebral aneurysmal subarachnoid hemorrhage (aSAH). Methods. The approach of Bayesian neural networks with fuzzy logic inferences was applied to data from five trials of Tirilazad for aneurysmal subarachnoid hemorrhage (3551 patients). Results. Bayesian meta-analyses of observational studies on aSAH prognostic factors gave generalizable posterior distributions of population mean log odd ratios (ORs). Similar trends were noted in Bayesian and linear regression ORs. Significant outcome predictors include normal motor response, cerebral infarction, history of myocardial infarction, cerebral edema, history of diabetes mellitus, fever on day 8, prior subarachnoid hemorrhage, admission angiographic vasospasm, neurological grade, intraventricular hemorrhage, ruptured aneurysm size, history of hypertension, vasospasm day, age and mean arterial pressure. Heteroscedasticity was present in the nontransformed dataset. Artificial neural networks found nonlinear relationships with 11 hidden variables in 1 layer, using the multilayer perceptron model. Fuzzy logic decision rules (centroid defuzzification technique) denoted cut-off points for poor prognosis at greater than 2.5 clusters. Discussion. This aSAH prognostic system makes use of existing knowledge, recognizes unknown areas, incorporates one's clinical reasoning, and compensates for uncertainty in prognostication. PMID:23690884
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.
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
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.
Christiansen, H; Sahin, K; Berthold, F; Hero, B; Terpe, H J; Lampert, F
1995-01-01
A comparison of the prognostic impact of five molecular variables in a large series was made, including tests of their nonrandom association and multivariate analysis. Molecular data were available for 377 patients and MYCN amplification, cytogenetic chromosome 1p deletion, loss of chromosome 1p heterozygosity, DNA ploidy and CD44 expression were investigated. Their interdependence and influence on event-free survival was tested uni- and multivariately using Pearson's chi 2-test, Kaplan-Meier estimates, log rank tests and the Cox's regression model. MYCN amplification was present in 18% (58/322) of cases and predicted poorer prognosis in localised (P < 0.001), metastatic (P = 0.002) and even 4S (P = 0.040) disease. CD44 expression was found in 86% (127/148) of cases, and was a marker for favourable outcome in patients with neuroblastoma stages 1-3 (P = 0.003) and 4 (P = 0.017). Chromosome 1p deletion was cytogenetically detected in 51% (28/55), and indicated reduced event-free survival in localised neuroblastoma (P = 0.020). DNA ploidy and loss of heterozygosity on chromosome 1p were of less prognostic value. Most factors of prognostic significance were associated with each other. By multivariate analysis, MYCN was selected as the only relevant factor. Risk estimation of high discriminating power is, therefore, possible for patients with localised and metastatic neuroblastoma using stage and MYCN.
Gao, Haiyan; Yang, Mei; Zhang, Xiaolan
2018-04-01
The present study aimed to investigate potential recurrence-risk biomarkers based on significant pathways for Luminal A breast cancer through gene expression profile analysis. Initially, the gene expression profiles of Luminal A breast cancer patients were downloaded from The Cancer Genome Atlas database. The differentially expressed genes (DEGs) were identified using a Limma package and the hierarchical clustering analysis was conducted for the DEGs. In addition, the functional pathways were screened using Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses and rank ratio calculation. The multigene prognostic assay was exploited based on the statistically significant pathways and its prognostic function was tested using train set and verified using the gene expression data and survival data of Luminal A breast cancer patients downloaded from the Gene Expression Omnibus. A total of 300 DEGs were identified between good and poor outcome groups, including 176 upregulated genes and 124 downregulated genes. The DEGs may be used to effectively distinguish Luminal A samples with different prognoses verified by hierarchical clustering analysis. There were 9 pathways screened as significant pathways and a total of 18 DEGs involved in these 9 pathways were identified as prognostic biomarkers. According to the survival analysis and receiver operating characteristic curve, the obtained 18-gene prognostic assay exhibited good prognostic function with high sensitivity and specificity to both the train and test samples. In conclusion the 18-gene prognostic assay including the key genes, transcription factor 7-like 2, anterior parietal cortex and lymphocyte enhancer factor-1 may provide a new method for predicting outcomes and may be conducive to the promotion of precision medicine for Luminal A breast cancer.
Mocellin, Simone; Pasquali, Sandro; Rossi, Carlo Riccardo; Nitti, Donato
2011-07-01
The proportion of positive among examined lymph nodes (lymph node ratio [LNR]) has been recently proposed as an useful and easy-to-calculate prognostic factor for patients with cutaneous melanoma. However, its independence from the standard prognostic system TNM has not been formally proven in a large series of patients. Patients with histologically proven cutaneous melanoma were identified from the Surveillance Epidemiology End Results database. Disease-specific survival was the clinical outcome of interest. The prognostic ability of conventional factors and LNR was assessed by multivariable survival analysis using the Cox regression model. Eligible patients (n = 8,177) were diagnosed with melanoma between 1998 and 2006. Among lymph node-positive cases (n = 3,872), most LNR values ranged from 1% to 10% (n = 2,187). In the whole series (≥5 lymph nodes examined) LNR significantly contributed to the Cox model independently of the TNM effect on survival (hazard ratio, 1.28; 95% confidence interval, 1.23-1.32; P < .0001). On subgroup analysis, the significant and independent prognostic value of LNR was confirmed both in patients with ≥10 lymph nodes examined (n = 4,381) and in those with TNM stage III disease (n = 3,658). In all cases, LNR increased the prognostic accuracy of the survival model. In this large series of patients, the LNR independently predicted disease-specific survival, improving the prognostic accuracy of the TNM system. Accordingly, the LNR should be taken into account for the stratification of patients' risk, both in clinical and research settings. Copyright © 2011 Mosby, Inc. All rights reserved.
Ishizuka, Mitsuru; Nagata, Hitoshi; Takagi, Kazutoshi; Horie, Toru; Kubota, Keiichi
2007-12-01
To investigate the significance of preoperative Glasgow prognostic score (GPS) for postoperative prognostication of patients with colorectal cancer. Recent studies have revealed that the GPS, an inflammation-based prognostic score that includes only C-reactive protein (CRP) and albumin, is a useful tool for predicting postoperative outcome in cancer patients. However, few studies have investigated the GPS in the field of colorectal surgery. The GPS was calculated on the basis of admission data as follows: patients with an elevated level of both CRP (>10 mg/L) and hypoalbuminemia (Alb <35 g/L) were allocated a score of 2, and patients showing 1 or none of these blood chemistry abnormalities were allocated a score of 1 or 0, respectively. Prognostic significance was analyzed by univariate and multivariate analyses. A total of 315 patients were evaluated. Kaplan-Meier analysis and log-rank test revealed that a higher GPS predicted a higher risk of postoperative mortality (P < 0.01). Univariate analyses revealed that postoperative TNM was the most sensitive predictor of postoperative mortality (odds ratio, 0.148; 95% confidence interval, 0.072-0.304; P < 0.0001). Multivariate analyses using factors such as age, sex, tumor site, serum carcinoembryonic antigen, CA19-9, CA72-4, CRP, albumin, and GPS revealed that GPS (odds ratio, 0.165; 95% confidence interval, 0.037-0.732; P = 0.0177) was associated with postoperative mortality. Preoperative GPS is considered to be a useful predictor of postoperative mortality in patients with colorectal cancer.
Hagiwara, Kazuhisa; Tobisawa, Yuki; Kaya, Takatoshi; Kaneko, Tomonori; Hatakeyama, Shingo; Mori, Kazuyuki; Hashimoto, Yasuhiro; Koie, Takuya; Suda, Yoshihiko; Ohyama, Chikara; Yoneyama, Tohru
2017-01-01
Wisteria floribunda agglutinin (WFA) preferably binds to LacdiNAc glycans, and its reactivity is associated with tumor progression. The aim of this study to examine whether the serum LacdiNAc carrying prostate-specific antigen–glycosylation isomer (PSA-Gi) and WFA-reactivity of tumor tissue can be applied as a diagnostic and prognostic marker of prostate cancer (PCa). Between 2007 and 2016, serum PSA-Gi levels before prostate biopsy (Pbx) were measured in 184 biopsy-proven benign prostatic hyperplasia patients and 244 PCa patients using an automated lectin-antibody immunoassay. WFA-reactivity on tumor was analyzed in 260 radical prostatectomy (RP) patients. Diagnostic and prognostic performance of serum PSA-Gi was evaluated using area under the receiver-operator characteristic curve (AUC). Prognostic performance of WFA-reactivity on tumor was evaluated via Cox proportional hazards regression analysis and nomogram. The AUC of serum PSA-Gi detecting PCa and predicting Pbx Grade Group (GG) 3 and GG ≥ 3 after RP was much higher than those of conventional PSA. Multivariate analysis showed that WFA-reactivity on prostate tumor was an independent risk factor of PSA recurrence. The nomogram was a strong model for predicting PSA-free survival provability with a c-index ≥0.7. Serum PSA-Gi levels and WFA-reactivity on prostate tumor may be a novel diagnostic and pre- and post-operative prognostic biomarkers of PCa, respectively. PMID:28134773
Hagiwara, Kazuhisa; Tobisawa, Yuki; Kaya, Takatoshi; Kaneko, Tomonori; Hatakeyama, Shingo; Mori, Kazuyuki; Hashimoto, Yasuhiro; Koie, Takuya; Suda, Yoshihiko; Ohyama, Chikara; Yoneyama, Tohru
2017-01-26
Wisteria floribunda agglutinin (WFA) preferably binds to LacdiNAc glycans, and its reactivity is associated with tumor progression. The aim of this study to examine whether the serum LacdiNAc carrying prostate-specific antigen-glycosylation isomer (PSA-Gi) and WFA-reactivity of tumor tissue can be applied as a diagnostic and prognostic marker of prostate cancer (PCa). Between 2007 and 2016, serum PSA-Gi levels before prostate biopsy (Pbx) were measured in 184 biopsy-proven benign prostatic hyperplasia patients and 244 PCa patients using an automated lectin-antibody immunoassay. WFA-reactivity on tumor was analyzed in 260 radical prostatectomy (RP) patients. Diagnostic and prognostic performance of serum PSA-Gi was evaluated using area under the receiver-operator characteristic curve (AUC). Prognostic performance of WFA-reactivity on tumor was evaluated via Cox proportional hazards regression analysis and nomogram. The AUC of serum PSA-Gi detecting PCa and predicting Pbx Grade Group (GG) 3 and GG ≥ 3 after RP was much higher than those of conventional PSA. Multivariate analysis showed that WFA-reactivity on prostate tumor was an independent risk factor of PSA recurrence. The nomogram was a strong model for predicting PSA-free survival provability with a c -index ≥0.7. Serum PSA-Gi levels and WFA-reactivity on prostate tumor may be a novel diagnostic and pre- and post-operative prognostic biomarkers of PCa, respectively.
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
2011-09-01
predict disease free survival for cervix cancer (34% disease free survival (DFS) if IFP > 19 mmHg, 68% DFS if IFP < 19 mmHg (p = 0.002)) [11]. Thus, the...pressure predicts survival in patients with cervix cancer independent of clinical prognostic factors and tumor oxygen measurements. Cancer Res...Estimation for Monitoring Breast Cancer Response to Neoadjuvant Therapy PRINCIPAL INVESTIGATOR: Flemming Forsberg, Ph.D
The prognostic value of sleep patterns in disorders of consciousness in the sub-acute phase.
Arnaldi, Dario; Terzaghi, Michele; Cremascoli, Riccardo; De Carli, Fabrizio; Maggioni, Giorgio; Pistarini, Caterina; Nobili, Flavio; Moglia, Arrigo; Manni, Raffaele
2016-02-01
This study aimed to evaluate, through polysomnographic analysis, the prognostic value of sleep patterns, compared to other prognostic factors, in patients with disorders of consciousness (DOCs) in the sub-acute phase. Twenty-seven patients underwent 24-h polysomnography and clinical evaluation 3.5 ± 2 months after brain injury. Their clinical outcome was assessed 18.5 ± 9.9 months later. Polysomnographic recordings were evaluated using visual and quantitative indexes. A general linear model was applied to identify features able to predict clinical outcome. Clinical status at follow-up was analysed as a function of the baseline clinical status, the interval between brain injury and follow-up evaluation, patient age and gender, the aetiology of the injury, the lesion site, and visual and quantitative sleep indexes. A better clinical outcome was predicted by a visual index indicating the presence of sleep integrity (p=0.0006), a better baseline clinical status (p=0.014), and younger age (p=0.031). Addition of the quantitative sleep index strengthened the prediction. More structured sleep emerged as a valuable predictor of a positive clinical outcome in sub-acute DOC patients, even stronger than established predictors (e.g. age and baseline clinical condition). Both visual and quantitative sleep evaluation could be helpful in predicting clinical outcome in sub-acute DOCs. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
Biomarkers for the early detection of relapses in metastatic colorectal cancers.
Chereches, Gabriela; Barbos, Otilia; Buiga, Rares; Balacescu, Ovidiu; Iancu, Dana; Todor, Nicolae; Balacescu, Loredana; Miron, Nicu; Bejinariu, Nona; Ciuleanu, Tudor-Eliade
2017-01-01
To assess prognostic/predictive value of carcinoembryonic antigen (CEA), transthyretin (TRT), αenolase (NNE), β2-microglobulin (β2-micro), B-cell activating factor (BAFF) and circulating tumor cells (CTCs) in metastatic colorectal cancer (mCRC) patients treated with chemotherapy with or without bevacizumab. 72 histologically confirmed mCRC patients treated at Oncology Institute Cluj were included. Biomarker levels were measured through validated methods. A manual method was used for CTCs, involving hemolysis, cytospin centrifugation and immunocytochemical staining for pan-cytokeratin. Statistical endpoints were response, progression- free survival (PFS) and overall survival (OS). Initial chemotherapy was fluoropyrimidine/oxaliplatin-based in 93.1%; bevacizumab was added in 58.3% of the patients. Median PFS and OS were 16.4 and 24.4 months. Two-year OS for CR & PR vs SD vs PD were 90% vs 48% vs 12%, respectively (p<0.01). Two-year OS for chemo/ bevacizumab vs chemotherapy: 65% vs 42% (p=0.09). Baseline CEA ≥5 ng/ml had a negative prognostic impact on OS and PFS (p<0.01). High baseline CEA was predictive of improved OS when adding bevacizumab (2-year OS chemo/bevacizumab vs chemo: 60% vs 17%, p<0.01); adding bevacizumab in patients with normal CEA did not improve OS (p=0.29). Higher than cut-off values for TRT had a positive OS prognostic value (p<0.01); higher levels for NNE, β2-microglobulin and BAFF had a negative impact (p<0.01). Two-year OS for baseline <1 CTC/ml vs ≥1 CTC/ ml was 74% vs 64% respectively (p=0.15). The evaluated biomarkers could be useful prognostic factors for survival. Baseline CEA also has predictive value, suggesting that patients with low levels do not benefit from bevacizumab. A non-statistically significant correlation was observed between the number of CTCs and outcome.
Ion channel gene expression predicts survival in glioma patients
Wang, Rong; Gurguis, Christopher I.; Gu, Wanjun; Ko, Eun A; Lim, Inja; Bang, Hyoweon; Zhou, Tong; Ko, Jae-Hong
2015-01-01
Ion channels are important regulators in cell proliferation, migration, and apoptosis. The malfunction and/or aberrant expression of ion channels may disrupt these important biological processes and influence cancer progression. In this study, we investigate the expression pattern of ion channel genes in glioma. We designate 18 ion channel genes that are differentially expressed in high-grade glioma as a prognostic molecular signature. This ion channel gene expression based signature predicts glioma outcome in three independent validation cohorts. Interestingly, 16 of these 18 genes were down-regulated in high-grade glioma. This signature is independent of traditional clinical, molecular, and histological factors. Resampling tests indicate that the prognostic power of the signature outperforms random gene sets selected from human genome in all the validation cohorts. More importantly, this signature performs better than the random gene signatures selected from glioma-associated genes in two out of three validation datasets. This study implicates ion channels in brain cancer, thus expanding on knowledge of their roles in other cancers. Individualized profiling of ion channel gene expression serves as a superior and independent prognostic tool for glioma patients. PMID:26235283
Xiang, Zuo-Lin; Zeng, Zhao-Chong; Fan, Jia; Tang, Zhao-You; Zeng, Hai-Ying
2012-05-01
In the present study, we evaluated the prognostic value of intratumoral and peritumoral expression of connective tissue growth factor (CTGF), transforming growth factor-beta 1 (TGF-β1), and interleukin-11 (IL-11) in patients with hepatocellular carcinoma (HCC) after curative resection. Expression of CTGF, TGF-β1, and IL-11 was assessed by immunohistochemical staining of tissue microarrays containing paired tumor and peritumoral liver tissue from 290 patients who had undergone hepatectomy for histologically proven HCC. The prognostic value of these and other clinicopathologic factors were evaluated. The median follow-up time was 54.3 months (range, 4.3-118.3 months). High intratumoral CTGF expression was associated with vascular invasion (P = 0.015), intratumoral IL-11 expression correlated with higher tumor node metastasis (TNM) stage (P = 0.009), and peritumoral CTGF overexpression correlated with lack of tumor encapsulation (P = 0.031). Correlation analysis of these proteins revealed that intratumoral CTGF and IL-11 correlated with high intratumoral TGF-β1 expression (r = 0.325, P < 0.001; and r = 0.273, P < 0.001, respectively). TNM stage (P < 0.001), high intratumoral CTGF levels (P = 0.010), and intratumoral IL-11 expression (P = 0.015) were independent prognostic factors for progression-free survival (PFS). Vascular invasion (P = 0.032), TNM stage (P < 0.001), high intratumoral CTGF levels (P = 0.036), and intratumoral IL-11 expression (P = 0.013) were independent prognostic factors for overall survival (OS). High intratumoral CTGF and intratumoral IL-11 expression were associated with PFS and OS after hepatectomy, and the combination of intratumoral CTGF with IL-11 may be predictive of survival.
Walter, R F H; Mairinger, F D; Ting, S; Vollbrecht, C; Mairinger, T; Theegarten, D; Christoph, D C; Schmid, K W; Wohlschlaeger, J
2015-03-03
Malignant pleural mesothelioma (MPM) is a highly aggressive tumour that is first-line treated with a combination of cisplatin and pemetrexed. Until now, predictive and prognostic biomarkers are lacking, making it a non-tailored therapy regimen with unknown outcome. P53 is frequently inactivated in MPM, but mutations are extremely rare. MDM2 and P14/ARF are upstream regulators of P53 that may contribute to P53 inactivation. A total of 72 MPM patients were investigated. MDM2 immunoexpression was assessed in 65 patients. MDM2 and P14/ARF mRNA expression was analysed in 48 patients of the overall collective. The expression results were correlated to overall survival (OS) and progression-free survival (PFS). OS and PFS correlated highly significantly with MDM2 mRNA and protein expression, showing a dismal prognosis for patients with elevated MDM2 expression (for OS: Score (logrank) test: P⩽0.002, and for PFS: Score (logrank) test; P<0.007). MDM2 was identified as robust prognostic and predictive biomarker for MPM on the mRNA and protein level. P14/ARF mRNA expression reached no statistical significance, but Kaplan-Meier curves distinguished patients with low P14/ARF expression and hence shorter survival from patients with higher expression and prolonged survival. MDM2 is a prognostic and predictive marker for a platin-pemetrexed therapy of patients with MPMs. Downregulation of P14/ARF expression seems to contribute to MDM2-overexpression-mediated P53 inactivation in MPM patients.
Montalban-Bravo, Guillermo; Takahashi, Koichi; Patel, Keyur; Wang, Feng; Xingzhi, Song; Nogueras, Graciela M.; Huang, Xuelin; Pierola, Ana Alfonso; Jabbour, Elias; Colla, Simona; Gañan-Gomez, Irene; Borthakur, Gautham; Daver, Naval; Estrov, Zeev; Kadia, Tapan; Pemmaraju, Naveen; Ravandi, Farhad; Bueso-Ramos, Carlos; Chamseddine, Ali; Konopleva, Marina; Zhang, Jianhua; Kantarjian, Hagop; Futreal, Andrew; Garcia-Manero, Guillermo
2018-01-01
The prognostic and predictive value of sequencing analysis in myelodysplastic syndromes (MDS) has not been fully integrated into clinical practice. We performed whole exome sequencing (WES) of bone marrow samples from 83 patients with MDS and 31 with MDS/MPN identifying 218 driver mutations in 31 genes in 98 (86%) patients. A total of 65 (57%) patients received therapy with hypomethylating agents. By univariate analysis, mutations in BCOR, STAG2, TP53 and SF3B1 significantly influenced survival. Increased number of mutations (≥ 3), but not clonal heterogeneity, predicted for shorter survival and LFS. Presence of 3 or more mutations also predicted for lower likelihood of response (26 vs 50%, p = 0.055), and shorter response duration (3.6 vs 26.5 months, p = 0.022). By multivariate analysis, TP53 mutations (HR 3.1, CI 1.3–7.5, p = 0.011) and number of mutations (≥ 3) (HR 2.5, CI 1.3–4.8, p = 0.005) predicted for shorter survival. A novel prognostic model integrating this mutation data with IPSS-R separated patients into three categories with median survival of not reached, 29 months and 12 months respectively (p < 0.001) and increased stratification potential, compared to IPSS-R, in patients with high/very-high IPSS-R. This model was validated in a separate cohort of 413 patients with untreated MDS. Although the use of WES did not provide significant more information than that obtained with targeted sequencing, our findings indicate that increased number of mutations is an independent prognostic factor in MDS and that mutation data can add value to clinical prognostic models. PMID:29515765
Montalban-Bravo, Guillermo; Takahashi, Koichi; Patel, Keyur; Wang, Feng; Xingzhi, Song; Nogueras, Graciela M; Huang, Xuelin; Pierola, Ana Alfonso; Jabbour, Elias; Colla, Simona; Gañan-Gomez, Irene; Borthakur, Gautham; Daver, Naval; Estrov, Zeev; Kadia, Tapan; Pemmaraju, Naveen; Ravandi, Farhad; Bueso-Ramos, Carlos; Chamseddine, Ali; Konopleva, Marina; Zhang, Jianhua; Kantarjian, Hagop; Futreal, Andrew; Garcia-Manero, Guillermo
2018-02-09
The prognostic and predictive value of sequencing analysis in myelodysplastic syndromes (MDS) has not been fully integrated into clinical practice. We performed whole exome sequencing (WES) of bone marrow samples from 83 patients with MDS and 31 with MDS/MPN identifying 218 driver mutations in 31 genes in 98 (86%) patients. A total of 65 (57%) patients received therapy with hypomethylating agents. By univariate analysis, mutations in BCOR, STAG2, TP53 and SF3B1 significantly influenced survival. Increased number of mutations (≥ 3), but not clonal heterogeneity, predicted for shorter survival and LFS. Presence of 3 or more mutations also predicted for lower likelihood of response (26 vs 50%, p = 0.055), and shorter response duration (3.6 vs 26.5 months, p = 0.022). By multivariate analysis, TP53 mutations (HR 3.1, CI 1.3-7.5, p = 0.011) and number of mutations (≥ 3) (HR 2.5, CI 1.3-4.8, p = 0.005) predicted for shorter survival. A novel prognostic model integrating this mutation data with IPSS-R separated patients into three categories with median survival of not reached, 29 months and 12 months respectively ( p < 0.001) and increased stratification potential, compared to IPSS-R, in patients with high/very-high IPSS-R. This model was validated in a separate cohort of 413 patients with untreated MDS. Although the use of WES did not provide significant more information than that obtained with targeted sequencing, our findings indicate that increased number of mutations is an independent prognostic factor in MDS and that mutation data can add value to clinical prognostic models.
Alodaibi, Faris A; Minick, Kate I; Fritz, Julie M
2013-11-18
Lumbar disc herniation (LDH) surgery is usually recommended when conservative treatments fail to manage patients' symptoms. However, many patients undergoing LDH surgery continue to report pain and disability. Preoperative psychological factors have shown to be predictive for postoperative outcomes. Our aim was to systematically review studies that prospectively examined the prognostic value of factors in the Fear Avoidance Model (FAM), including back pain, leg pain, catastrophizing, anxiety, fear-avoidance, depression, physical activity and disability, to predict postoperative outcomes in patients undergoing LDH surgery. We performed a systematic literature review of prospective studies that measured any FAM factors preoperatively to predict postoperative outcomes for patients undergoing LDH surgery. Our search databases included PubMed, CINAHL, and PsycINFO. We assessed the quality of each included study using a certain quality assessment list. Degree of agreement between reviewers on quality assessment was examined. Results related to FAM factors in the included studies were summarized. Thirteen prospective studies met our inclusion criteria. Most studies were considered high quality. Heterogeneity was present between the included studies in many aspects. The most common FAM factors examinered were baseline pain, disability and depression. In, general, depression, fear-avoidance behaviors, passive pain coping, and anxiety FAM factors appeared to have negative influence on LDH surgical outcome. Baseline back pain and leg pain appeared to have differing prognostic value on LDH surgical outcomes. FAM factors seem to influence LDH surgical outcomes. Patients with high levels of depression, anxiety and fear-avoidance behaviors are more likely to have poor outcomes following LDH surgery. Conversely, high levels of leg pain, but not back pain seem to be predictor for favorable LDH surgery outcome. More research is needed to determine the exact role of FAM factors on LDH surgical outcome and the value for screening for these factors.
Prognostic and survival analysis of 837 Chinese colorectal cancer patients.
Yuan, Ying; Li, Mo-Dan; Hu, Han-Guang; Dong, Cai-Xia; Chen, Jia-Qi; Li, Xiao-Fen; Li, Jing-Jing; Shen, Hong
2013-05-07
To develop a prognostic model to predict survival of patients with colorectal cancer (CRC). Survival data of 837 CRC patients undergoing surgery between 1996 and 2006 were collected and analyzed by univariate analysis and Cox proportional hazard regression model to reveal the prognostic factors for CRC. All data were recorded using a standard data form and analyzed using SPSS version 18.0 (SPSS, Chicago, IL, United States). Survival curves were calculated by the Kaplan-Meier method. The log rank test was used to assess differences in survival. Univariate hazard ratios and significant and independent predictors of disease-specific survival and were identified by Cox proportional hazard analysis. The stepwise procedure was set to a threshold of 0.05. Statistical significance was defined as P < 0.05. The survival rate was 74% at 3 years and 68% at 5 years. The results of univariate analysis suggested age, preoperative obstruction, serum carcinoembryonic antigen level at diagnosis, status of resection, tumor size, histological grade, pathological type, lymphovascular invasion, invasion of adjacent organs, and tumor node metastasis (TNM) staging were positive prognostic factors (P < 0.05). Lymph node ratio (LNR) was also a strong prognostic factor in stage III CRC (P < 0.0001). We divided 341 stage III patients into three groups according to LNR values (LNR1, LNR ≤ 0.33, n = 211; LNR2, LNR 0.34-0.66, n = 76; and LNR3, LNR ≥ 0.67, n = 54). Univariate analysis showed a significant statistical difference in 3-year survival among these groups: LNR1, 73%; LNR2, 55%; and LNR3, 42% (P < 0.0001). The multivariate analysis results showed that histological grade, depth of bowel wall invasion, and number of metastatic lymph nodes were the most important prognostic factors for CRC if we did not consider the interaction of the TNM staging system (P < 0.05). When the TNM staging was taken into account, histological grade lost its statistical significance, while the specific TNM staging system showed a statistically significant difference (P < 0.0001). The overall survival of CRC patients has improved between 1996 and 2006. LNR is a powerful factor for estimating the survival of stage III CRC patients.
Suzuki, Hideaki; Tabata, Takahisa; Koizumi, Hiroki; Hohchi, Nobusuke; Takeuchi, Shoko; Kitamura, Takuro; Fujino, Yoshihisa; Ohbuchi, Toyoaki
2014-12-01
This study aimed to create a multiple regression model for predicting hearing outcomes of idiopathic sudden sensorineural hearing loss (ISSNHL). The participants were 205 consecutive patients (205 ears) with ISSNHL (hearing level ≥ 40 dB, interval between onset and treatment ≤ 30 days). They received systemic steroid administration combined with intratympanic steroid injection. Data were examined by simple and multiple regression analyses. Three hearing indices (percentage hearing improvement, hearing gain, and posttreatment hearing level [HLpost]) and 7 prognostic factors (age, days from onset to treatment, initial hearing level, initial hearing level at low frequencies, initial hearing level at high frequencies, presence of vertigo, and contralateral hearing level) were included in the multiple regression analysis as dependent and explanatory variables, respectively. In the simple regression analysis, the percentage hearing improvement, hearing gain, and HLpost showed significant correlation with 2, 5, and 6 of the 7 prognostic factors, respectively. The multiple correlation coefficients were 0.396, 0.503, and 0.714 for the percentage hearing improvement, hearing gain, and HLpost, respectively. Predicted values of HLpost calculated by the multiple regression equation were reliable with 70% probability with a 40-dB-width prediction interval. Prediction of HLpost by the multiple regression model may be useful to estimate the hearing prognosis of ISSNHL. © The Author(s) 2014.
Yang, Chan Joo; Roh, Jong-Lyel; Choi, Kyoung Hyo; Kim, Min-Ju; Choi, Seung-Ho; Nam, Soon Yuhl; Kim, Sang Yoon
2015-05-15
The prognostic role of swallowing-related, pretreatment subjective and objective findings has not been investigated in detail. The authors evaluated the association between pretreatment MD Anderson Dysphagia Inventory (MDADI) or videofluorographic swallowing study (VFSS) results and standard outcomes, including early recurrence and survival, in patients with treatment-naïve head and neck squamous cell carcinoma (HNSCC). Patients with HNSCC (n = 191) who received treatment at the authors' institution and were examined by self-administered MDADI questionnaires and VFSS were prospectively enrolled. MDADI and VFSS findings were analyzed in correlation with clinicopathologic variables, and factors that predicted 2-year disease-free survival (DFS) and overall survival (OS) were identified using a Cox proportional-hazards regression model. The 2-year OS and DFS rates were 80.1% and 77.5%, respectively. Clinical tumor (T) and lymph node (N) classifications, overall TNM stage, sex, tumor site, and educational level were significantly associated with specific MDADI subdomains, whereas Karnofsky performance score was significantly associated with all MDADI subdomains. After controlling for clinical factors, total scores, global assessment scores, and emotional and physical MDADI subscores were significantly predictive of 2-year OS and DFS (P < .05 for each). VFSS findings were not significantly associated with survival (P > .05). The current results provide evidence of the prognostic role of the MDADI in predicting early survival outcomes in patients with HNSCC. The MDADI may be a practical and noninvasive method for the identification of patients at risk who would benefit from close follow-up. © 2015 American Cancer Society.
Harimoto, Norifumi; Yoshizumi, Tomoharu; Sakata, Kazuhito; Nagatsu, Akihisa; Motomura, Takashi; Itoh, Shinji; Harada, Noboru; Ikegami, Toru; Uchiyama, Hideaki; Soejima, Yuji; Maehara, Yoshihiko
2017-11-01
In recent years, the establishment of new staging systems for hepatocellular carcinoma (HCC) has been reported worldwide. The system combining albumin-bilirubin (ALBI) with tumor-node-metastasis stage, developed by the Liver Cancer Study Group of Japan, was called the ALBI-T score. Patient data were retrospectively collected for 357 consecutive patients who had undergone hepatic resection for HCC with curative intent between January 2004 and December 2015. The overall survival and recurrence-free survival were compared by the Kaplan-Meier method, using different staging systems: the Japan integrated staging (JIS), modified JIS, and ALBI-T. Multivariate analysis identified five poor prognostic factors (higher age, poor differentiation, the presence of microvascular invasion, the presence of intrahepatic metastasis, and blood transfusion) that influenced overall survival, and four poor prognostic factors (the presence of intrahepatic metastasis, serum α-fetoprotein level, blood transfusion, and each staging system (JIS, modified JIS, and ALBI-T score)) that influenced recurrence-free survival. Patients for each these three staging system had a significantly worse prognosis regarding recurrence-free survival, but not with overall survival. The modified JIS score showed the lowest Akaike information criteria statistic value, indicating it had the best ability to predict overall survival compared with the other staging systems. This retrospective analysis showed that, in post-hepatectomy patients with HCC, the ALBI-T score is predictive of worse recurrence-free survival, even when adjustments are made for other known predictors. However, modified JIS is better than ALBI-T in predicting overall survival. © 2017 The Japan Society of Hepatology.
Prognostic factors for acute myeloid leukaemia in adults--biological significance and clinical use.
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.
Molecular Pathology: Predictive, Prognostic, and Diagnostic Markers in Uterine Tumors.
Ritterhouse, Lauren L; Howitt, Brooke E
2016-09-01
This article focuses on the diagnostic, prognostic, and predictive molecular biomarkers in uterine malignancies, in the context of morphologic diagnoses. The histologic classification of endometrial carcinomas is reviewed first, followed by the description and molecular classification of endometrial epithelial malignancies in the context of histologic classification. Taken together, the molecular and histologic classifications help clinicians to approach troublesome areas encountered in clinical practice and evaluate the utility of molecular alterations in the diagnosis and subclassification of endometrial carcinomas. Putative prognostic markers are reviewed. The use of molecular alterations and surrogate immunohistochemistry as prognostic and predictive markers is also discussed. Copyright © 2016 Elsevier Inc. All rights reserved.
Press, Oliver W; Unger, Joseph M; Rimsza, Lisa M; Friedberg, Jonathan W; LeBlanc, Michael; Czuczman, Myron S; Kaminski, Mark; Braziel, Rita M; Spier, Catherine; Gopal, Ajay K; Maloney, David G; Cheson, Bruce D; Dakhil, Shaker R; Miller, Thomas P; Fisher, Richard I
2013-12-01
There is currently no consensus on optimal frontline therapy for patients with follicular lymphoma. We analyzed a phase III randomized intergroup trial comparing six cycles of CHOP-R (cyclophosphamide-Adriamycin-vincristine-prednisone (Oncovin)-rituximab) with six cycles of CHOP followed by iodine-131 tositumomab radioimmunotherapy (RIT) to assess whether any subsets benefited more from one treatment or the other, and to compare three prognostic models. We conducted univariate and multivariate Cox regression analyses of 532 patients enrolled on this trial and compared the prognostic value of the FLIPI (follicular lymphoma international prognostic index), FLIPI2, and LDH + β2M (lactate dehydrogenase + β2-microglobulin) models. Outcomes were excellent, but not statistically different between the two study arms [5-year progression-free survival (PFS) of 60% with CHOP-R and 66% with CHOP-RIT (P = 0.11); 5-year overall survival (OS) of 92% with CHOP-R and 86% with CHOP-RIT (P = 0.08); overall response rate of 84% for both arms]. The only factor found to potentially predict the impact of treatment was serum β2M; among patients with normal β2M, CHOP-RIT patients had better PFS compared with CHOP-R patients, whereas among patients with high serum β2M, PFS by arm was similar (interaction P value = 0.02). All three prognostic models (FLIPI, FLIPI2, and LDH + β2M) predicted both PFS and OS well, though the LDH + β2M model is easiest to apply and identified an especially poor risk subset. In an exploratory analysis using the latter model, there was a statistically significant trend suggesting that low-risk patients had superior observed PFS if treated with CHOP-RIT, whereas high-risk patients had a better PFS with CHOP-R. ©2013 AACR.
Addison, Christina L; Ding, Keyue; Seymour, Lesley; Zhao, Huijun; Laurie, Scott A; Shepherd, Frances A; Goss, Glenwood D; Bradbury, Penelope A
2015-11-01
Prognostic and predictive ability of circulating vascular endothelial growth factor (VEGF), stromal derived factor (SDF)-1α and soluble VEGF receptors (sVEGFR) 2 and 3, were evaluated in non-small cell lung cancer (NSCLC) patients enrolled in NCIC Clinical Trials Group BR. 24 comparing chemotherapy with or without cediranib. Biomarker levels were assessed by ELISA in serum from 149/296 enrolled patients at baseline and 146/149 patients after one treatment cycle. Experimental cut-offs for baseline measures determined using a graphic method were: < or ≥1 ng/ml, SDF-1α: ≤ or >3.5 ng/ml, sVEGFR2: < or ≥11 ng/ml and sVEGFR3: < or ≥35.5 ng/ml. Changes in markers from baseline to on-treatment were predefined as increased ≥10%, stable within 10% or decreased ≥10%. Cox regression models were used to correlate biomarkers with patient characteristics and outcomes including progression-free survival (PFS) and overall survival (OS). No baseline biomarker was prognostic for OS, however, high baseline sVEGFR2 was prognostic for better PFS (p=0.0008) in the chemotherapy alone arm. Low baseline sVEGFR2 or sVEGFR3 were predictive of PFS benefit from cediranib (interaction p=0.06 and p=0.05, respectively). While on treatment, VEGF-A increases were associated with better PFS (p=0.02) and OS (p=0.01) for cediranib treated patients. Decreases in sVEGFR2 (p=0.01) or sVEGFR3 (p=0.02) were also predictive of better OS in cediranib treated patients. Low baseline sVEGFR2 and sVEGFR3 were predictive for PFS benefit from cediranib, whereas increases in VEGF-A and decreases in sVEGFR2 or sVEGFR3 levels from baseline to on-treatment were predictive of an OS benefit from cediranib in chemotherapy treated NSCLC patients. Validation of these results is warranted. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
Ryu, In Sun; Kim, Jae Seung; Roh, Jong-Lyel; Cho, Kyung-Ja; Choi, Seung-Ho; Nam, Soon Yuhl; Kim, Sang Yoon
2014-03-01
Metabolic tumour volume (MTV) and total lesion glycolysis (TLG) from (18)F-FDG PET/CT are emerging prognostic biomarkers in human solid cancers; yet few studies have investigated their clinical and prognostic significance in oral cavity squamous cell carcinoma (OSCC). The present retrospective study evaluated the utility of pretreatment MTV and TLG measured by (18)F-FDG PET/CT to predict survival and occult metastasis (OM) in OSCC. Of 162 patients with OSCC evaluated preoperatively by (18)F-FDG PET/CT, 105 who underwent definitive surgery with or without adjuvant therapy were eligible. Maximum standardized uptake value (SUVmax), MTV and TLG were measured. For calculation of MTV, 3-D regions of interest were drawn and a SUV threshold of 2.5 was used for defining regions. Univariate and multivariate analyses identified clinicopathological and imaging variables associated with OM, disease-free survival (DFS) and overall survival (OS). The median (range) SUVmax, MTV and TLG were 7.3 (0.7-41.9), 4.5 ml (0.7-115.1 ml) and 18.3 g (2.4-224.1 g), respectively. Of 53 patients with clinically negative lymph nodes, OM was detected in 19 (36%). By univariate and multivariate analyses, MTV (P = 0.018) and TLG (P = 0.011) were both independent predictive factors for OM, although they were not independent of each other. The 4-year DFS and OS rates were 53.0% and 62.0%, respectively. Univariate and multivariate analyses revealed that MTV (P = 0.001) and TLG (P = 0.006), with different cut-off levels, were both independent predictive factors for DFS, although they were not independent of each other, and MTV (P = 0.001), TLG (P = 0.002) and the involved resection margin (P = 0.007) were independent predictive factors for OS. Pretreatment MTV and TLG may be useful in stratifying the likelihood of survival and predicting OM in OSCC.
Evaluation of an inflammation-based prognostic score in patients with metastatic renal cancer.
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.
Autophagy-related prognostic signature for breast cancer.
Gu, Yunyan; Li, Pengfei; Peng, Fuduan; Zhang, Mengmeng; Zhang, Yuanyuan; Liang, Haihai; Zhao, Wenyuan; Qi, Lishuang; Wang, Hongwei; Wang, Chenguang; Guo, Zheng
2016-03-01
Autophagy is a process that degrades intracellular constituents, such as long-lived or damaged proteins and organelles, to buffer metabolic stress under starvation conditions. Deregulation of autophagy is involved in the progression of cancer. However, the predictive value of autophagy for breast cancer prognosis remains unclear. First, based on gene expression profiling, we found that autophagy genes were implicated in breast cancer. Then, using the Cox proportional hazard regression model, we detected autophagy prognostic signature for breast cancer in a training dataset. We identified a set of eight autophagy genes (BCL2, BIRC5, EIF4EBP1, ERO1L, FOS, GAPDH, ITPR1 and VEGFA) that were significantly associated with overall survival in breast cancer. The eight autophagy genes were assigned as a autophagy-related prognostic signature for breast cancer. Based on the autophagy-related signature, the training dataset GSE21653 could be classified into high-risk and low-risk subgroups with significantly different survival times (HR = 2.72, 95% CI = (1.91, 3.87); P = 1.37 × 10(-5)). Inactivation of autophagy was associated with shortened survival of breast cancer patients. The prognostic value of the autophagy-related signature was confirmed in the testing dataset GSE3494 (HR = 2.12, 95% CI = (1.48, 3.03); P = 1.65 × 10(-3)) and GSE7390 (HR = 1.76, 95% CI = (1.22, 2.54); P = 9.95 × 10(-4)). Further analysis revealed that the prognostic value of the autophagy signature was independent of known clinical prognostic factors, including age, tumor size, grade, estrogen receptor status, progesterone receptor status, ERBB2 status, lymph node status and TP53 mutation status. Finally, we demonstrated that the autophagy signature could also predict distant metastasis-free survival for breast cancer. © 2015 Wiley Periodicals, Inc.
Registrar Staging Assistant (SEER*RSA) - SEER
Use this site for cases diagnosed 2018 and forward to code Extent of Disease 2018, Summary Stage 2018, Site-Specific Data Items, and Grade. Use it for 2016 and 2017 cases to determine UICC TNM 7th edition stage, Collaborative Stage v.02.05.50, and Site-Specific predictive and prognostic factors.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Cui, Yi; Global Institution for Collaborative Research and Education, Hokkaido University, Sapporo; Song, Jie
Purpose: To identify prognostic biomarkers in pancreatic cancer using high-throughput quantitative image analysis. Methods and Materials: In this institutional review board–approved study, we retrospectively analyzed images and outcomes for 139 locally advanced pancreatic cancer patients treated with stereotactic body radiation therapy (SBRT). The overall population was split into a training cohort (n=90) and a validation cohort (n=49) according to the time of treatment. We extracted quantitative imaging characteristics from pre-SBRT {sup 18}F-fluorodeoxyglucose positron emission tomography, including statistical, morphologic, and texture features. A Cox proportional hazard regression model was built to predict overall survival (OS) in the training cohort using 162more » robust image features. To avoid over-fitting, we applied the elastic net to obtain a sparse set of image features, whose linear combination constitutes a prognostic imaging signature. Univariate and multivariate Cox regression analyses were used to evaluate the association with OS, and concordance index (CI) was used to evaluate the survival prediction accuracy. Results: The prognostic imaging signature included 7 features characterizing different tumor phenotypes, including shape, intensity, and texture. On the validation cohort, univariate analysis showed that this prognostic signature was significantly associated with OS (P=.002, hazard ratio 2.74), which improved upon conventional imaging predictors including tumor volume, maximum standardized uptake value, and total legion glycolysis (P=.018-.028, hazard ratio 1.51-1.57). On multivariate analysis, the proposed signature was the only significant prognostic index (P=.037, hazard ratio 3.72) when adjusted for conventional imaging and clinical factors (P=.123-.870, hazard ratio 0.53-1.30). In terms of CI, the proposed signature scored 0.66 and was significantly better than competing prognostic indices (CI 0.48-0.64, Wilcoxon rank sum test P<1e-6). Conclusion: Quantitative analysis identified novel {sup 18}F-fluorodeoxyglucose positron emission tomography image features that showed improved prognostic value over conventional imaging metrics. If validated in large, prospective cohorts, the new prognostic signature might be used to identify patients for individualized risk-adaptive therapy.« less
Prognostic value of inflammation-based scores in patients with osteosarcoma
Liu, Bangjian; Huang, Yujing; Sun, Yuanjue; Zhang, Jianjun; Yao, Yang; Shen, Zan; Xiang, Dongxi; He, Aina
2016-01-01
Systemic inflammation responses have been associated with cancer development and progression. C-reactive protein (CRP), Glasgow prognostic score (GPS), neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), lymphocyte-monocyte ratio (LMR), and neutrophil-platelet score (NPS) have been shown to be independent risk factors in various types of malignant tumors. This retrospective analysis of 162 osteosarcoma cases was performed to estimate their predictive value of survival in osteosarcoma. All statistical analyses were performed by SPSS statistical software. Receiver operating characteristic (ROC) analysis was generated to set optimal thresholds; area under the curve (AUC) was used to show the discriminatory abilities of inflammation-based scores; Kaplan-Meier analysis was performed to plot the survival curve; cox regression models were employed to determine the independent prognostic factors. The optimal cut-off points of NLR, PLR, and LMR were 2.57, 123.5 and 4.73, respectively. GPS and NLR had a markedly larger AUC than CRP, PLR and LMR. High levels of CRP, GPS, NLR, PLR, and low level of LMR were significantly associated with adverse prognosis (P < 0.05). Multivariate Cox regression analyses revealed that GPS, NLR, and occurrence of metastasis were top risk factors associated with death of osteosarcoma patients. PMID:28008988
Maimaiti, Yusufu; Dong, Lingling; Aili, Aikebaier; Maimaitiaili, Maimaitiaili; Huang, Tao; Abudureyimu, Kelimu
2017-07-04
Bcl-2 interacting mediator of cell death (Bim) appears to have contradictory roles in cancer. It is uncertain whether Bim show prognostic significance in patients with breast cancer. To investigate the correlation between Bim expression and clinicopathological characteristics of breast cancer and to evaluate Bim's effect on overall survival (OS). We used immunohistochemistry (IHC) technique to detect the expression of Bim via tissue microarray in 275 breast cancer samples, Kaplan-Meier analysis to perform survival analysis, and Cox proportional hazards regression model to explore the risk factors of breast cancer. The results revealed that Bim expression was significantly correlated with age, estrogen receptor (ER) and/or progesterone receptor (PR), human epidermal growth factor receptor (HER2) and Ki67 expression (P< 0.05). Bim expression was significantly different in the four molecular subtypes (P= 0.000). Survival analysis showed that Bim positive expression contributed to a shorter OS (P= 0.034), especially in patients with luminal A tumors (P= 0.039). Univariate and multivariate regression analysis showed that Bim was an independent prognostic factor for breast cancer (P< 0.05). Bim may serve as an effective predictive factor for lower OS in breast cancer patients, especially in those with luminal A tumors.
El Sayed, Mohamed E; Bahadur, Yasir A; Hassouna, Ashraf H; Fawzy, Ehab E; Nasr, Azza M; Sadiq, Bakr B; Dada, Reyad; Sait, Khalid H; Anfinan, Nisrin M
2017-10-01
This study evaluated the survival outcome, pattern of failure and prognostic factors in cervix uteri cancer patients. We reviewed the data of 60 patients with stages IB-IVA cancer who were treated between January 2004 and December 2010. Most patients (n = 50; 83%) had squamous cell carcinoma. Stage IIB was the most common presentation (n = 41; 68%). Forty-seven patients (78%) received Cisplatin concurrent with radiotherapy (CRT). The 2- and 4-year overall survival (OS) was 82% and 79%, respectively. Prolongation of the overall treatment time (OAT) for greater than 56 days, advanced stage and pretreatment hemoglobin (Hb) levels (<10 g/dL) negatively predicted OS (P = 0.039, P = 0.044 and P = 0.008, respectively). The 2- and 4-year disease-free survival (DFS) rates were 80% and 69%, respectively. Vaginal infiltration and brachytherapy (orthogonal versus CT-based planning) were significant factors for the prediction of relapse (P = 0.048 and P = 0.049, respectively). The 2- and 4-year loco-regional control (LRC) rates were 78% and 70%, respectively, and the distant metastasis-free survival (DMFS) rates were 82% and 79%, respectively. Vaginal infiltration was the only negative predictive factor for LRC (P = 0.045), and pathological tumor grade was the only factor indicative of distant metastases (P = 0.037). Grade 3 or 4 late rectal reactions were reported in two patients (3%), and no patients developed grade 3 or 4 urinary reactions. The treatment results in our cervix uteri cancer patients and the prognostic factors are comparable to those of previous reports. Orthogonal brachytherapy planning and vaginal infiltration negatively predicted relapse. © 2016 John Wiley & Sons Australia, Ltd.
Design and validation of a model to predict early mortality in haemodialysis patients.
Mauri, Joan M; Clèries, Montse; Vela, Emili
2008-05-01
Mortality and morbidity rates are higher in patients receiving haemodialysis therapy than in the general population. Detection of risk factors related to early death in these patients could be of aid for clinical and administrative decision making. Objectives. The aims of this study were (1) to identify risk factors (comorbidity and variables specific to haemodialysis) associated with death in the first year following the start of haemodialysis and (2) to design and validate a prognostic model to quantify the probability of death for each patient. An analysis was carried out on all patients starting haemodialysis treatment in Catalonia during the period 1997-2003 (n = 5738). The data source was the Renal Registry of Catalonia, a mandatory population registry. Patients were randomly divided into two samples: 60% (n = 3455) of the total were used to develop the prognostic model and the remaining 40% (n = 2283) to validate the model. Logistic regression analysis was used to construct the model. One-year mortality in the total study population was 16.5%. The predictive model included the following variables: age, sex, primary renal disease, grade of functional autonomy, chronic obstructive pulmonary disease, malignant processes, chronic liver disease, cardiovascular disease, initial vascular access and malnutrition. The analyses showed adequate calibration for both the sample to develop the model and the validation sample (Hosmer-Lemeshow statistic 0.97 and P = 0.49, respectively) as well as adequate discrimination (ROC curve 0.78 in both cases). Risk factors implicated in mortality at one year following the start of haemodialysis have been determined and a prognostic model designed. The validated, easy-to-apply model quantifies individual patient risk attributable to various factors, some of them amenable to correction by directed interventions.
Han, Jae Hyun; Kim, Dong Goo; Na, Gun Hyung; Kim, Eun Young; Lee, Soo Ho; Hong, Tae Ho; You, Young Kyoung
2014-01-01
AIM: To select appropriate patients before surgical resection for hepatocellular carcinoma (HCC), especially those with advanced tumors. METHODS: From January 2000 to December 2012, we retrospectively analyzed the medical records of 298 patients who had undergone surgical resections for HCC with curative intent at our hospital. We evaluated preoperative prognostic factors associated with histologic grade of tumor, recurrence and survival, especially the findings of pre-operative imaging studies such as positron emission tomography-computed tomography (PET-CT) and magnetic resonance imaging (MRI). And then, we established a scoring system to predict recurrence and survival after surgery dividing the patients into two groups based on a tumor size of 5 cm. RESULTS: Of the 298 patients, 129 (43.3%) developed recurrence during the follow-up period. The 5 year disease free survival and overall survival were 47.0% and 58.7% respectively. In multivariate analysis, a serum alpha-fetoprotein (AFP) level of > 100 ng/mL and a standardized uptake value (SUV) of PET-CT of > 3.5 were predictive factors for histologic grade of tumor, recurrence, and survival. Tumor size of > 5 cm and a relative enhancement ratio (RER) calculated from preoperative MRI were also significantly associated with prognosis in univariate analysis. We established a scoring system to predict prognosis using AFP, SUV, and RER. In those with tumors of > 5 cm, it showed predicted both recurrence (P = 0.005) and survival (P = 0.001). CONCLUSION: The AFP, tumor size, SUV and RER are useful for prognosis preoperatively. An accurate prediction of prognosis is possible using our scoring system in large size tumors. PMID:25493027
Han, Jae Hyun; Kim, Dong Goo; Na, Gun Hyung; Kim, Eun Young; Lee, Soo Ho; Hong, Tae Ho; You, Young Kyoung
2014-12-07
To select appropriate patients before surgical resection for hepatocellular carcinoma (HCC), especially those with advanced tumors. From January 2000 to December 2012, we retrospectively analyzed the medical records of 298 patients who had undergone surgical resections for HCC with curative intent at our hospital. We evaluated preoperative prognostic factors associated with histologic grade of tumor, recurrence and survival, especially the findings of pre-operative imaging studies such as positron emission tomography-computed tomography (PET-CT) and magnetic resonance imaging (MRI). And then, we established a scoring system to predict recurrence and survival after surgery dividing the patients into two groups based on a tumor size of 5 cm. Of the 298 patients, 129 (43.3%) developed recurrence during the follow-up period. The 5 year disease free survival and overall survival were 47.0% and 58.7% respectively. In multivariate analysis, a serum alpha-fetoprotein (AFP) level of > 100 ng/mL and a standardized uptake value (SUV) of PET-CT of > 3.5 were predictive factors for histologic grade of tumor, recurrence, and survival. Tumor size of > 5 cm and a relative enhancement ratio (RER) calculated from preoperative MRI were also significantly associated with prognosis in univariate analysis. We established a scoring system to predict prognosis using AFP, SUV, and RER. In those with tumors of > 5 cm, it showed predicted both recurrence (P = 0.005) and survival (P = 0.001). The AFP, tumor size, SUV and RER are useful for prognosis preoperatively. An accurate prediction of prognosis is possible using our scoring system in large size tumors.
Machinery health prognostics: A systematic review from data acquisition to RUL prediction
NASA Astrophysics Data System (ADS)
Lei, Yaguo; Li, Naipeng; Guo, Liang; Li, Ningbo; Yan, Tao; Lin, Jing
2018-05-01
Machinery prognostics is one of the major tasks in condition based maintenance (CBM), which aims to predict the remaining useful life (RUL) of machinery based on condition information. A machinery prognostic program generally consists of four technical processes, i.e., data acquisition, health indicator (HI) construction, health stage (HS) division, and RUL prediction. Over recent years, a significant amount of research work has been undertaken in each of the four processes. And much literature has made an excellent overview on the last process, i.e., RUL prediction. However, there has not been a systematic review that covers the four technical processes comprehensively. To fill this gap, this paper provides a review on machinery prognostics following its whole program, i.e., from data acquisition to RUL prediction. First, in data acquisition, several prognostic datasets widely used in academic literature are introduced systematically. Then, commonly used HI construction approaches and metrics are discussed. After that, the HS division process is summarized by introducing its major tasks and existing approaches. Afterwards, the advancements of RUL prediction are reviewed including the popular approaches and metrics. Finally, the paper provides discussions on current situation, upcoming challenges as well as possible future trends for researchers in this field.
New prognostic model for extranodal natural killer/T cell lymphoma, nasal type.
Cai, Qingqing; Luo, Xiaolin; Zhang, Guanrong; Huang, Huiqiang; Huang, Hui; Lin, Tongyu; Jiang, Wenqi; Xia, Zhongjun; Young, Ken H
2014-09-01
Extranodal natural killer/T cell lymphoma, nasal type (ENKTL) is an aggressive disease with a poor prognosis, requiring risk stratification in affected patients. We designed a new prognostic model specifically for ENKTL to identify high-risk patients who need more aggressive therapy. We retrospectively reviewed 158 patients who were newly diagnosed with ENKTL. The estimated 5-year overall survival rate was 39.4 %. Independent prognostic factors included total protein (TP) <60 g/L, fasting blood glucose (FBG) >100 mg/dL, and Korean Prognostic Index (KPI) score ≥2. We constructed a new prognostic model by combining these prognostic factors: group 1 (64 cases (41.0 %)), no adverse factors; group 2 (58 cases (37.2 %)), one adverse factor; and group 3 (34 cases (21.8 %)), two or three adverse factors. The 5-year overall survival (OS) rates of these groups were 66.7, 23.0, and 5.9 %, respectively (p < 0.001). Our new prognostic model had a better prognostic value than did the KPI model alone (p < 0.001). Our proposed prognostic model for ENKTL, including the newly identified prognostic indicators, TP and FBG, demonstrated a balanced distribution of patients into different risk groups with better prognostic discrimination compared with the KPI model alone.
Yun, Man Soo; Kim, Seong-Jang; Pak, Kyoungjune; Lee, Chang Hun
2015-01-01
We compared the prognostic ability of the maximum standardized uptake value (SUVmax) and various biological marker expressions to predict recurrence in patients with surgically resected cervical cancer. A retrospective review identified 60 patients with cervical cancer who received [18F]fluorodeoxyglucose positron emission tomography/computed tomography (F-18 FDG PET/CT) at the time of the diagnosis of cancer. The SUVmax, expressions of carbonic anhydrase-IX (CA-IX), glucose transporter 1 (GLUT-1), and vascular endothelial growth factor (VEGF), and known prognostic factors were investigated. The median follow-up time was 22.2 months (range 3.4-43.1 months). Using univariate analyses, the stage (stage II, p = 0.0066), SUVmax (> 6, p = 0.027), parametrial involvement (p < 0.0001), and positivity for CA-IX (p = 0.0191) were associated with recurrences of cervical cancer. With the Cox proportional hazard regression model, the SUVmax was a potent predictor for disease-free survival (DFS). Although CA-IX expression was related to DFS in the current study, the potent predictor for DFS was SUVmax. Therefore, SUVmax is of greater prognostic value than biological marker expression in patients with surgically resected cervical cancer. © 2015 S. Karger GmbH, Freiburg.
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.
2013-01-01
Background With the wide application of targeted drug therapies, the relevance of prognostic and predictive markers in patient selection has become increasingly important. Bevacizumab is commonly used in combination with chemotherapy in the treatment of metastatic colorectal cancer. However, there are currently no predictive or prognostic biomarkers for bevacizumab. Several clinical studies have evaluated bevacizumab-induced hypertension in patients with metastatic colorectal cancer. This meta-analysis was performed to better determine the association of bevacizumab-induced hypertension with outcome in patients with metastatic colorectal cancer, and to assess whether bevacizumab-induced hypertension can be used as a prognostic factor in these patients. Methods We performed a systematic review and meta-analysis on seven published studies to investigate the relationship between hypertension and outcome of patients with metastatic colorectal cancer treated with bevacizumab. Our primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS) and overall response rate (ORR). Hazard ratios (HRs) for PFS and OS were extracted from each trial, and the log of the relative risk ratio (RR) was estimated for ORR. Results The occurrence of bevacizumab-induced hypertension in patients was highly associated with improvements in PFS (HR = 0.57, 95% CI: 0.46–0.72; P <0.001), OS (HR = 0.50; 95% CI: 0.37–0.68; P <0.001), and ORR (RR = 1.57, 95% CI: 1.07–2.30, P <0.05), as compared to patients without hypertension. Conclusions Bevacizumab-induced hypertension may represent a prognostic factor in patients with metastatic colorectal cancer. PMID:24283603
Chan, Hiang Ping; Mukhopadhyay, Amartya; Chong, Pauline Lee Poh; Chin, Sally; Wong, Xue Yun; Ong, Venetia; Chan, Yiong Huak; Lim, Tow Keang; Phua, Jason
2017-01-01
COPD is a complex condition with a heavy burden of disease. Many multidimensional tools have been studied for their prognostic utility but none has been universally adopted as each has its own limitations. We hypothesize that a multidimensional tool examining four domains, health-related quality of life, disease severity, systemic effects of disease and patient factors, would better categorize and prognosticate these patients. We first evaluated 300 patients and found four factors that predicted mortality: BMI, airflow obstruction, St George's Respiratory Questionnaire and age (BOSA). A 10-point index (BOSA index) was constructed and prospectively validated in a cohort of 772 patients with all-cause mortality as the primary outcome. Patients were categorized into their respective BOSA quartile group based on their BOSA score. Multivariate survival analyses and receiver operator characteristic (ROC) curves were used to assess the BOSA index. Patients in BOSA Group 4 were at higher risk of death compared with their counterparts in Group 1 (hazard ratio (HR): 0.29, 95% CI: 0.16-0.51, P < 0.001) and Group 2 (HR: 0.53, 95% CI: 0.34-0.82, P = 0.005). Race and gender did not affect mortality. The area under the ROC curve for BOSA index was 0.690 ± 0.025 while that for Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2011 was 0.641 ± 0.025 (P = 0.17). The BOSA index predicts mortality well and it has at least similar prognostic utility as GOLD 2011 in Asian patients. The BOSA index is a simple tool that does not require complex equipment or testing. It has the potential to be used widely. © 2016 Asian Pacific Society of Respirology.
Nonomura, Norio; Takayama, Hitoshi; Nakayama, Masashi; Nakai, Yasutomo; Kawashima, Atsunari; Mukai, Masatoshi; Nagahara, Akira; Aozasa, Katsuyuki; Tsujimura, Akira
2011-06-01
• To evaluate tumour-associated macrophage (TAM) infiltration in prostate biopsy specimens as a possible prognostic factor for prostate cancer (PCa) after hormonal therapy. • Immunostaining of TAMs in prostate biopsy specimens was performed using a monoclonal antibody CD68 for 71 patients having PCa treated with hormonal therapy. • Six microscopic (×400) fields around the cancer foci were selected for TAM counting. • The median value of serum prostate-specific antigen (PSA) was 50.1 ng/mL, and the median TAM count was 22. • Recurrence-free survival was significantly better in patients with fewer TAMs (<22) than in those with higher numbers of TAMs (≥22) (P < 0.001). • TAM count was higher in those with higher serum PSA (PSA), higher Gleason score, clinical T stage or those with PSA failure. Cox multivariate analysis showed that TAM count is one of the prognostic factors for PCa treated by hormonal therapy (P < 0.0001). • TAM infiltration in prostate needle biopsy specimens is a useful predictive factor for PSA failure or progression of PCa after hormonal therapy. © 2010 THE AUTHORS. BJU INTERNATIONAL © 2010 BJU INTERNATIONAL.
Anichini, Andrea; Tassi, Elena; Grazia, Giulia; Mortarini, Roberta
2018-06-01
Immunotherapy of non-small cell lung cancer (NSCLC), by immune checkpoint inhibitors, has profoundly improved the clinical management of advanced disease. However, only a fraction of patients respond and no effective predictive factors have been defined. Here, we discuss the prospects for identification of such predictors of response to immunotherapy, by fostering an in-depth analysis of the immune landscape of NSCLC. The emerging picture, from several recent studies, is that the immune contexture of NSCLC lesions is a complex and heterogeneous feature, as documented by analysis for frequency, phenotype and spatial distribution of innate and adaptive immune cells, and by characterization of functional status of inhibitory receptor + T cells. The complexity of the immune landscape of NSCLC stems from the interaction of several factors, including tumor histology, molecular subtype, main oncogenic drivers, nonsynonymous mutational load, tumor aneuploidy, clonal heterogeneity and tumor evolution, as well as the process of epithelial-mesenchymal transition. All these factors contribute to shape NSCLC immune profiles that have clear prognostic significance. An integrated analysis of the immune and molecular profile of the neoplastic lesions may allow to define the potential predictive role of the immune landscape for response to immunotherapy.
Model-Based Prognostics of Hybrid Systems
NASA Technical Reports Server (NTRS)
Daigle, Matthew; Roychoudhury, Indranil; Bregon, Anibal
2015-01-01
Model-based prognostics has become a popular approach to solving the prognostics problem. However, almost all work has focused on prognostics of systems with continuous dynamics. In this paper, we extend the model-based prognostics framework to hybrid systems models that combine both continuous and discrete dynamics. In general, most systems are hybrid in nature, including those that combine physical processes with software. We generalize the model-based prognostics formulation to hybrid systems, and describe the challenges involved. We present a general approach for modeling hybrid systems, and overview methods for solving estimation and prediction in hybrid systems. As a case study, we consider the problem of conflict (i.e., loss of separation) prediction in the National Airspace System, in which the aircraft models are hybrid dynamical systems.
Ashraf, Mohammed; Souka, Ahmed; Adelman, Ron A
2018-03-01
To assess predictors of treatment response in neovascular age-related macular degeneration (AMD) in an attempt to develop a patient-centric treatment algorithm. We conducted a systematic search using PubMed, EMBASE and Web of Science for prognostic indicators/predictive factors with the key words: 'age related macular degeneration', 'neovascular AMD', 'choroidal neovascular membrane (CNV)', 'anti-vascular endothelial growth factor (anti-VEGF)', 'aflibercept', 'ranibizumab', 'bevacizumab', 'randomized clinical trials', 'post-hoc', 'prognostic', 'predictive', 'response' 'injection frequency, 'treat and extend (TAE), 'pro re nata (PRN)', 'bi-monthly' and 'quarterly'. We only included studies that had an adequate period of follow-up (>1 year), a single predefined treatment regimen with a predetermined re-injection criteria, an adequate number of patients, specific morphological [optical coherence tomography (OCT)] criteria that predicted final visual outcomes and injection frequency and did not include switching from one drug to the other. We were able to identify seven prospective studies and 16 retrospective studies meeting our inclusion criteria. There are several morphological and demographic prognostic indicators that can predict response to therapy in wet AMD. Smaller CNV size, subretinal fluid (SRF), retinal angiomatous proliferation (RAP) and response to therapy at 12 weeks (visual, angiographic or OCT) can all predict good visual outcomes in patients receiving anti-VEGF therapy. Patients with larger CNV, older age, pigment epithelial detachment (PED), intraretinal cysts (IRC) and vitreomacular adhesion (VMA) achieved less visual gains. Patients having VMA/VMT required more intensive treatment with increased treatment frequency. Patients with both posterior vitreous detachment (PVD) and SRF require infrequent injections. Patients with PED are prone to recurrences of fluid activity with a reduction in visual acuity (VA). A regimen that involves less intensive therapy and extended follow-up intervals (4 weekly) can be suggested for patients who show adequate visual response and have both SRF and PVD at baseline. In addition, patients with poor prognostic indicators such as IRC, VMA, large CNV size, older age and poor response at 12 weeks should be extended very cautiously with the possibility of fixed monthly/bimonthly (every 2 months) treatments if they fail to achieve dryness. Patients with PED at baseline should receive monthly/bimonthly injections of anti-VEGF therapy or can be extended very cautiously (two weekly intervals) using a TAE protocol. © 2017 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.
Puente, Javier; López-Tarruella, Sara; Ruiz, Amparo; Lluch, Ana; Pastor, Miguel; Alba, Emilio; de la Haba, Juan; Ramos, Manuel; Cirera, Luis; Antón, Antonio; Llombart, Antoni; Plazaola, Arrate; Fernández-Aramburo, Antonio; Sastre, Javier; Díaz-Rubio, Eduardo; Martin, Miguel
2010-07-01
Women with recurrent metastatic breast cancer from a Spanish hospital registry (El Alamo, GEICAM) were analyzed in order to identify the most helpful prognostic factors to predict survival and to ultimately construct a practical prognostic index. The inclusion criteria covered women patients diagnosed with operable invasive breast cancer who had metastatic recurrence between 1990 and 1997 in GEICAM hospitals. Patients with stage IV breast cancer at initial diagnosis or with isolated loco-regional recurrence were excluded from this analysis. Data from 2,322 patients with recurrent breast cancer after primary treatment (surgery, radiation and systemic adjuvant treatment) were used to construct the prognostic index. The prognostic index score for each individual patient was calculated by totalling up the scores of each independent variable. The maximum score obtainable was 26.1. Nine-hundred and sixty-two patients who had complete data for all the variables were used in the computation of the prognostic index score. We were able to stratify them into three prognostic groups based on the prognostic index score: 322 patients in the good risk group (score < or =13.5), 308 patients in the intermediate risk group (score 13.51-15.60) and 332 patients in the poor risk group (score > or =15.61). The median survivals for these groups were 3.69, 2.27 and 1.02 years, respectively (P < 0.0001). In conclusion, risk scores are extraordinarily valuable tools, highly recommendable in the clinical practice.
Luen, Stephen; Wong, Siew Wei; Mar, Victoria; Kelly, John W; McLean, Catriona; McArthur, Grant A; Haydon, Andrew
2018-01-01
Stage IV melanoma exhibits a diverse range of tumor biology from indolent to aggressive disease. Many important prognostic factors have already been identified. Despite this, the behavior of metastatic melanoma remains difficult to predict. We sought to determine if any primary tumor characteristics affect survival following the diagnosis of stage IV melanoma. All patients diagnosed with stage IV melanoma between January 2003 and December 2012 were identified from the Victorian Melanoma Service database. Retrospective chart review was performed to collect data on primary tumor characteristics (thickness, ulceration, mitotic rate, melanoma subtype, or occult primary). Known and suspected prognostic factors were additionally collected (time to diagnosis of stage IV disease, age, sex, stage, receipt of chemotherapy, and era of recurrence). The effect of primary tumor characteristics on overall survival from the date of diagnosis of stage IV disease was assessed. A total of 227 patients with a median follow-up of 5 years from diagnosis of stage IV disease were identified. Median overall survival of the cohort was 250 days.Of the primary tumor characteristics assessed, only tumor thickness affected survival from diagnosis of stage IV disease, hazard ratio=1.09 (1.02 to 1.16), P=0.008. This remained significant in multivariate analysis, P=0.007. Other primary tumor characteristics did not significantly influence survival. Primary tumor thickness is a significant prognostic factor in stage IV melanoma. Our data suggest that the biology of the primary melanoma may persist to influence the behavior of metastatic disease.
Unal, Olcun Umit; Oztop, Ilhan; Yasar, Nurgul; Urakci, Zuhat; Ozatli, Tahsin; Bozkurt, Oktay; Sevinc, Alper; Gunaydin, Yusuf; Yapar Taskoylu, Burcu; Arpaci, Erkan; Ulas, Arife; Kodaz, Hilmi; Tonyali, Onder; Avci, Nilufer; Aksoy, Asude; Yilmaz, Ahmet Ugur
2015-01-01
Background Soft tissue sarcomas (STSs) are rare malignant tumors of embryogenic mesoderm origin. Primary thoracic STSs account for a small percentage of all STSs and limited published information is available. This study aimed to identify the prognostic factors for thoracic STSs and evaluate the disease's clinical outcomes. Methods The medical records of 109 patients with thoracic STSs who were treated between 2003 and 2013 were retrospectively reviewed. Patients' survival rates were analyzed and potential prognostic factors evaluated. Results The median follow-up period was 29 months (range: 1–121 months). STSs were most frequently localized on the chest wall (n = 42; 38.5%) and lungs (n = 42; 38.5%). The most common histological types were malignant fibrous histiocytoma (n = 23; 21.1%), liposarcoma (n = 17; 15.6%), and leiomyosarcoma (n = 16; 14.7%). The median survival time of all patients was 40.3 months (95% confidence interval, 14.22–66.37 months), with one and five-year survival rates of 93.4% and 63.5%, respectively. Univariate analysis of all groups revealed that metastatic stage, unresectability, tumor diameter of >10 cm, tumor location other than the chest wall, and grade 3 diseases were predictable of poor survival. However, only grade 3 diseases and tumor location other than the chest wall were confirmed by multivariate analysis as poor prognostic factors. Conclusions Primary thoracic STSs are rarely seen malignant tumors. Our results indicated that patients with low-grade tumors and those localized on the chest wall often experienced better survival outcomes. PMID:26273340
Martin, Lisa; Watanabe, Sharon; Fainsinger, Robin; Lau, Francis; Ghosh, Sunita; Quan, Hue; Atkins, Marlis; Fassbender, Konrad; Downing, G Michael; Baracos, Vickie
2010-10-01
To determine whether elements of a standard nutritional screening assessment are independently prognostic of survival in patients with advanced cancer. A prospective nested cohort of patients with metastatic cancer were accrued from different units of a Regional Palliative Care Program. Patients completed a nutritional screen on admission. Data included age, sex, cancer site, height, weight history, dietary intake, 13 nutrition impact symptoms, and patient- and physician-reported performance status (PS). Univariate and multivariate survival analyses were conducted. Concordance statistics (c-statistics) were used to test the predictive accuracy of models based on training and validation sets; a c-statistic of 0.5 indicates the model predicts the outcome as well as chance; perfect prediction has a c-statistic of 1.0. A training set of patients in palliative home care (n = 1,164) was used to identify prognostic variables. Primary disease site, PS, short-term weight change (either gain or loss), dietary intake, and dysphagia predicted survival in multivariate analysis (P < .05). A model including only patients separated by disease site and PS with high c-statistics between predicted and observed responses for survival in the training set (0.90) and validation set (0.88; n = 603). The addition of weight change, dietary intake, and dysphagia did not further improve the c-statistic of the model. The c-statistic was also not altered by substituting physician-rated palliative PS for patient-reported PS. We demonstrate a high probability of concordance between predicted and observed survival for patients in distinct palliative care settings (home care, tertiary inpatient, ambulatory outpatient) based on patient-reported information.
Asadi, Hamed; Kok, Hong Kuan; Looby, Seamus; Brennan, Paul; O'Hare, Alan; Thornton, John
2016-12-01
To identify factors influencing outcome in brain arteriovenous malformations (BAVM) treated with endovascular embolization. We also assessed the feasibility of using machine learning techniques to prognosticate and predict outcome and compared this to conventional statistical analyses. A retrospective study of patients undergoing endovascular treatment of BAVM during a 22-year period in a national neuroscience center was performed. Clinical presentation, imaging, procedural details, complications, and outcome were recorded. The data was analyzed with artificial intelligence techniques to identify predictors of outcome and assess accuracy in predicting clinical outcome at final follow-up. One-hundred ninety-nine patients underwent treatment for BAVM with a mean follow-up duration of 63 months. The commonest clinical presentation was intracranial hemorrhage (56%). During the follow-up period, there were 51 further hemorrhagic events, comprising spontaneous hemorrhage (n = 27) and procedural related hemorrhage (n = 24). All spontaneous events occurred in previously embolized BAVMs remote from the procedure. Complications included ischemic stroke in 10%, symptomatic hemorrhage in 9.8%, and mortality rate of 4.7%. Standard regression analysis model had an accuracy of 43% in predicting final outcome (mortality), with the type of treatment complication identified as the most important predictor. The machine learning model showed superior accuracy of 97.5% in predicting outcome and identified the presence or absence of nidal fistulae as the most important factor. BAVMs can be treated successfully by endovascular techniques or combined with surgery and radiosurgery with an acceptable risk profile. Machine learning techniques can predict final outcome with greater accuracy and may help individualize treatment based on key predicting factors. Copyright © 2016 Elsevier Inc. All rights reserved.
Sun, Feng-Kai; Sun, Qi; Fan, Yu-Chen; Gao, Shuai; Zhao, Jing; Li, Feng; Jia, Yi-Bin; Liu, Chuan; Wang, Li-Yuan; Li, Xin-You; Ji, Xiang-Fen; Wang, Kai
2016-02-01
Methylation of tissue factor pathway inhibitor 2 (TFPI2) gene has been detected in hepatocellular carcinoma (HCC). However, the clinicopathologcial significance and prognostic value of TFPI2 methylation in HCC remains largely unknown. This study aimed to investigate the prognostic value of TFPI2 methylation in HCC after hepatectomy. Methylation status of TFPI2 gene was examined in 178 surgical specimens of HCC and 20 normal liver samples using methylation-specific polymerase chain reaction. Methylation of TFPI2 gene was detected in 44.9% (80 of 178) of primary HCC samples, 10.7% (19 of 178) of the corresponding non-tumorous liver samples, and 5.0% (1/20) of the normal liver samples. The mRNA concentrations of TFPI2 in primary HCC tissues were significantly lower than those in corresponding non-tumorous liver tissues and those in normal liver tissues. TFPI2 methylation was significantly associated with higher TNM stage. Patients with TFPI2 methylation demonstrated a significantly poorer prognosis than those without TFPI2 methylation for both overall survival and disease-free survival (P < 0.001, respectively). Multivariate analyses confirmed that TFPI2 methylation was an independent prognostic factor for both overall survival (P = 0.002) and disease-free survival (P = 0.000) in HCC after hepatectomy. Moreover, TFPI2 methylation was found to be the only independent predictor for early tumor recurrence of HCC after resection based on multivariate analysis (P = 0.002). Methylation of TFPI2 predicts high risk of advanced tumor stage, early tumor recurrence, and poor prognosis, and it could be a potential prognostic biomarker in patients with HCC after hepatectomy. © 2015 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.
Serrablo, A; Paliogiannis, P; Pulighe, F; Moro, S Saudi-Moro; Borrego-Estella, V; Attene, F; Scognamillo, F; Hörndler, C
2016-09-01
We evaluated the impacts of a series of novel histopathological factors on clinical-surgical outcomes and survival of patients who underwent surgery for colorectal cancer liver metastasis, with and without neoadjuvant chemotherapy. A prospective database including 150 consecutive patients who underwent 183 hepatic resections for metastatic colorectal cancer was evaluated. Among them, 74 (49.3%) received neoadjuvant chemotherapy before surgery. The histopathological factors studied were: a) microsatellitosis, b) type and pattern of tumour growth, c) nuclear grade and the number of mitoses/mm(2), d) perilesional pseudocapsule, e) intratumoural fibrosis, f) lesion cellularity, g) hypoxic-angiogenic perilesional growth pattern, and h) the tumour normal interface. Three or more metastatic lesions, R1 resection margins, and <50% tumour necrosis were prognostic factors for a worse OS, but only the former was confirmed to be an independent prognostic factor in the multivariate analysis. Furthermore, tumour fibrosis <40% and cellularity >10% were predictive of a worse neoadjuvant therapy response, but these findings were not confirmed in the multivariate analysis. Finally, tumour necrosis <50%, cellularity >10%, and TNI >0.5 mm were prognostic factors for a worse DFS and AS in the univariate but not in the multivariate analysis. Several factors seem to influence the outcomes of surgery for colorectal cancer liver metastasis, especially the number of the lesions, the margins of resection, the percentage of necrosis and fibrosis, as well as the cellularity and the TNI. Copyright © 2016 Elsevier Ltd. All rights reserved.
Choi, Ji Soo; Baek, Hyeon-Man; Kim, Suhkmann; Kim, Min Jung; Youk, Ji Hyun; Moon, Hee Jung; Kim, Eun-Kyung; Han, Kyung Hwa; Kim, Dong-hyun; Kim, Seung Il; Koo, Ja Seung
2012-01-01
The purpose of this study was to examine the correlation between high-resolution magic angle spinning (HR-MAS) magnetic resonance (MR) spectroscopy using core needle biopsy (CNB) specimens and histologic prognostic factors currently used in breast cancer patients. After institutional review board approval and informed consent were obtained for this study, CNB specimens were collected from 36 malignant lesions in 34 patients. Concentrations and metabolic ratios of various choline metabolites were estimated by HR-MAS MR spectroscopy using CNB specimens. HR-MAS spectroscopic values were compared according to histopathologic variables [tumor size, lymph node metastasis, histologic grade, status of estrogens receptor (ER), progesterone receptor (PR), HER2 (a receptor for human epidermal growth factor), and Ki-67, and triple negativity]. Multivariate analysis was performed with Orthogonal Projections to Latent Structure-Discriminant Analysis (OPLS-DA). HR-MAS MR spectroscopy quantified and discriminated choline metabolites in all CNB specimens of the 36 breast cancers. Several metabolite markers [free choline (Cho), phosphocholine (PC), creatine (Cr), taurine, myo-inositol, scyllo-inositol, total choline (tCho), glycine, Cho/Cr, tCho/Cr, PC/Cr] on HR-MAS MR spectroscopy were found to correlate with histologic prognostic factors [ER, PR, HER2, histologic grade, triple negativity, Ki-67, poor prognosis]. OPLS-DA multivariate models were generally able to discriminate the status of histologic prognostic factors (ER, PR, HER2, Ki-67) and prognosis groups. Our study suggests that HR-MAS MR spectroscopy using CNB specimens can predict tumor aggressiveness prior to surgery in breast cancer patients. In addition, it may be helpful in the detection of reliable markers for breast cancer characterization. PMID:23272149
Kumar, S K; Dispenzieri, A; Fraser, R; Mingwei, F; Akpek, G; Cornell, R; Kharfan-Dabaja, M; Freytes, C; Hashmi, S; Hildebrandt, G; Holmberg, L; Kyle, R; Lazarus, H; Lee, C; Mikhael, J; Nishihori, T; Tay, J; Usmani, S; Vesole, D; Vij, R; Wirk, B; Krishnan, A; Gasparetto, C; Mark, T; Nieto, Y; Hari, P; D'Souza, A
2018-04-01
Duration of initial disease response remains a strong prognostic factor in multiple myeloma (MM) particularly for upfront autologous hematopoietic cell transplant (AHCT) recipients. We hypothesized that new drug classes and combinations employed prior to AHCT as well as after post-AHCT relapse may have changed the natural history of MM in this population. We analyzed the Center for International Blood and Marrow Transplant Research database to track overall survival (OS) of MM patients receiving single AHCT within 12 months after diagnosis (N=3256) and relapsing early post-AHCT (<24 months), and to identify factors predicting for early vs late relapses (24-48 months post-AHCT). Over three periods (2001-2004, 2005-2008, 2009-2013), patient characteristics were balanced except for lower proportion of Stage III, higher likelihood of one induction therapy with novel triplets and higher rates of planned post-AHCT maintenance over time. The proportion of patients relapsing early was stable over time at 35-38%. Factors reducing risk of early relapse included lower stage, chemosensitivity, transplant after 2008 and post-AHCT maintenance. Shorter post-relapse OS was associated with early relapse, IgA MM, Karnofsky <90, stage III, >1 line of induction and lack of maintenance. Post-AHCT early relapse remains a poor prognostic factor, even though outcomes have improved over time.
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.
Pond, Gregory R; Di Lorenzo, Giuseppe; Necchi, Andrea; Eigl, Bernhard J; Kolinsky, Michael P; Chacko, Raju T; Dorff, Tanya B; Harshman, Lauren C; Milowsky, Matthew I; Lee, Richard J; Galsky, Matthew D; Federico, Piera; Bolger, Graeme; DeShazo, Mollie; Mehta, Amitkumar; Goyal, Jatinder; Sonpavde, Guru
2014-05-01
Prognostic factors in men with penile squamous cell carcinoma (PSCC) receiving systemic therapy are unknown. A prognostic classification system in this disease may facilitate interpretation of outcomes and guide rational drug development. We performed a retrospective analysis to identify prognostic factors in men with PSCC receiving first-line systemic therapy for advanced disease. Individual patient level data were obtained from 13 institutions to study prognostic factors in the context of first-line systemic therapy for advanced PSCC. Cox proportional hazards regression analysis was conducted to examine the prognostic effect of these candidate factors on progression-free survival (PFS) and overall survival (OS): age, stage, hemoglobin, neutrophil count, lymphocyte count, albumin, site of metastasis (visceral or nonvisceral), smoking, circumcision, regimen, ECOG performance status (PS), lymphovascular invasion, precancerous lesion, and surgery following chemotherapy. The effect of different treatments was then evaluated adjusting for factors in the prognostic model. The study included 140 eligible men. Mean age across all men was 57.0 years. Among them, 8.6%, 21.4%, and 70.0% of patients had stage 2, 3, and 4 diseases, respectively; 40.7% had ECOG PS ≥ 1, 47.4% had visceral metastases, and 73.6% received cisplatin-based chemotherapy. The multivariate model of poor prognostic factors included visceral metastases (P<0.001) and ECOG PS ≥ 1 (P<0.001) for both PFS and OS. A risk stratification model constructed with 0, 1, and both poor prognostic factors was internally validated and demonstrated moderate discriminatory ability (c-statistic of 0.657 and 0.677 for OS and PFS, respectively). The median OS for the entire population was 9 months. Median OS was not reached, 8, and 7 months for those with 0, 1, and both risk factors, respectively. Cisplatin-based regimens were associated with better OS (P = 0.017) but not PFS (P = 0.37) compared with noncisplatin-based regimens after adjusting for the 2 prognostic factors. In men with advanced PSCC receiving first-line systemic therapy, visceral metastases and ECOG PS ≥ 1 were poor prognostic factors. A prognostic model including these factors exhibited moderate discriminatory ability for outcomes and warrants external validation. Patients receiving cisplatin-based regimens exhibited better outcomes compared with noncisplatin-based regimens after adjusting for prognostic factors. © 2013 Published by Elsevier Inc.
Yin, Jun-Qiang; Fu, Yi-Wei; Xie, Xian-Biao; Cheng, Xiao-Yu; Yang, Xiao-Yu; Liu, Wei-Hai; Tu, Jian; Gao, Zhen-Hua; Shen, Jing-Nan
2018-06-01
Telangiectatic osteosarcoma (TOS), a rare variant of osteosarcoma, may be easily misdiagnosed as aneurysmal bone cyst (ABC). The aims of this study were to investigate the diagnostic and prognostic factors of TOS by reviewing our experience with TOS and to develop a diagnostic model that may distinguish TOS from ABC. We identified 51 cases of TOS treated at the First Affiliated Hospital of Sun Yat-Sen University from March 2001 to January 2016 and reviewed their records, imaging information and pathological studies. A diagnostic model was developed to differentiate TOS and ABC by Bayes discriminant analysis and was evaluated. The log-rank test was used to analyze the prognostic factors of TOS and to compare the outcome differences between TOS and other high-grade osteosarcoma subtypes. The multi-disciplinary diagnostic method employed that combined clinical, imaging, and pathological studies enhanced the diagnostic accuracy. Age 18 years or younger and pathologic fracture were more common among the TOS patients than among the ABC patients (P = .004 and .005, respectively). The average white blood cell (WBC), platelet, lactate dehydrogenase (LDH), and alkaline phosphatase (ALP) values of the TOS patients were higher than those of the ABC patients ( P = .002, .003, .007, and .007, respectively). Our diagnostic model, including the aforementioned factors, accurately predicted 62% and 78% of the TOS patients in the training and validation sets, respectively. The 5-year estimates of event-free survival and overall survival of the TOS patients were 52.5 ± 9.4% and 54.9 ± 8.8%, respectively, which were similar to those of patients with other osteosarcoma subtypes ( P = .950 and .615, respectively). Tumor volume and the LDH level were predictive prognostic factors ( P = .040 and .044) but not the presence of pathologic fracture or misdiagnosis ( P = .424 and .632, all respectively). The multi-disciplinary diagnostic method and diagnostic model based on predictive factors, i.e. , age, the presence of pathologic fracture, and platelet, LDH, ALP and WBC levels, aided the differentiation of TOS and ABC. Smaller tumors and normal LDH levels were associated with better outcomes.
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.
Lønvik, Kenneth; Sørbye, Sveinung W; Nilsen, Marit N; Paulssen, Ruth H
2014-01-01
Dicer and Drosha are important enzymes for processing microRNAs. Recent studies have exhibited possible links between expression of different miRNAs, levels of miRNA processing enzymes, and cancer prognosis. We have investigated the prognostic impact of Dicer and Drosha and their correlation with miR-126 expression in a large cohort of non-small cell lung cancer (NSCLC) patients. We aimed to find patient groups within the cohort that might have an advantage of receiving adjunctive therapies. Dicer expression in the cytoplasm and Drosha expression in the nucleus were evaluated by manual immunohistochemistry of tissue microarrays (TMAs), including tumor tissue samples from 335 patients with resected stages I to IIIA NSCLC. In addition, in situ hybridizations of TMAs for visualization of miR-126 were performed. Kaplan-Meier analysis was performed, and the log-rank test via SPSS v.22 was used for estimating significance levels. In patients with normal performance status (ECOG = 0, n = 197), high Dicer expression entailed a significantly better prognosis than low Dicer expression (P = 0.024). Dicer had no significant prognostic value in patients with reduced performance status (ECOG = 1-2, n = 138). High Drosha expression was significantly correlated with high levels of the microRNA 126 (miR-126) (P = 0.004). Drosha/miR-126 co-expression had a significant negative impact on the disease-specific survival (DSS) rate (P < 0.001). Multivariate analyses revealed that the interaction Dicer*Histology (P = 0.049) and Drosha/miR-126 co-expression (P = 0.033) were independent prognostic factors. In NSCLC patients with normal performance status, Dicer is a positive prognostic factor. The importance of Drosha as a prognostic factor in our material seems to be related to miR-126 and possibly other microRNAs.
Prognostic factors of phyllodes tumor of the breast.
Roa, Juan Carlos; Tapia, Oscar; Carrasco, Paula; Contreras, Enrique; Araya, Juan Carlos; Muñoz, Sergio; Roa, Iván
2006-06-01
The phyllodes tumor is characterized by its tendency to recur locally and occasionally to metastasize. The purpose of the present paper was to assess the prognostic value of clinical-morphological characteristics in patients with phyllodes tumor. Forty-seven cases of phyllodes tumors was studied; the World Health Organization classification was used and follow up was obtained. A total of 51%, 28% and 21% of the tumors were classified as benign, borderline and malignant, respectively. The adherence (P = 0.01), size >10 cm (P = 0.001), high mitotic activity (P = 0.03), infiltrative tumor margin (P = 0.0002) and type of surgery in malignant tumors (P = 0.02) proved to be good predictors of relapse. The presence of pain (P = 0.03), postmenopausal status (P < 0.04), heavy cellular pleomorphism (P = 0.007), high mitotic activity (P = 0.002), tumoral grade (P = 0.006) and metastasis (P < 0.00001) were prognostic factors of poor survival. Tumoral grade and some clinical-morphological characteristics of patients with phyllodes tumors have a significant impact on the prediction of its biological behavior.
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
Corrado, C; Santarelli, M T; Pavlovsky, S; Pizzolato, M
1989-12-01
Four hundred ten previously untreated multiple myeloma patients entered onto two consecutive Grupo Argentino de Tratamiento de la Leucemia Aguda (GATLA) protocols were analyzed to identify significant prognostic factors influencing survival. The univariate analysis selected the following variables: performance status, renal function, percentage of bone marrow plasma cells at diagnosis, hemoglobin, and age. A multivariate analysis showed that performance status, renal function, percentage of bone marrow plasma cells, hemoglobin, and age were the best predictive variables for survival. A score was assigned to each patient according to these variables, which led to their classification in three groups: good, intermediate, and poor risk, with a probability of survival of 26% and 10% at 96 months, and 5% at 56 months, and median survival of 60, 37, and 14 months, respectively (P = .0000). In our patient population, this model proved to be superior to the Durie-Salmon staging system in defining prognostic risk groups, and separating patients with significantly different risks within each Durie-Salmon stage.
Clinical impact of sentinel lymph node biopsy in patients with thick (>4 mm) melanomas.
White, Ian; Fortino, Jeanine; Curti, Brendan; Vetto, John
2014-05-01
The role of sentinel lymph node status (SLNS) in thick melanoma is evolving. The purpose of this study was to determine the prognostic value of SLNS in thick melanoma. A retrospective analysis of 120 prospectively collected clinically node-negative thick melanomas over 5 years was performed. Patient (age/sex) and tumor (thickness, ulceration, SLNS, mitoses, metastases, and recurrence) features were collected. Multivariate analysis was performed using Cox proportional hazard model. Factors predictive of positive SLN included male sex, ulceration, and high mitoses. Factors associated with positive SLN had higher local-regional recurrence and metastases than negative SLN. SLNS and tumor thickness impacted 5-year disease-free survival (DFS) and overall survival (OS). Positive SLN, ulceration, age, and mitoses were independent predictors of DFS/OS. Nonulcerated/lower mitoses thick melanomas had lower positive SLN rates. Positive SLN develop recurrence and metastases and have worse OS/DFS. SLNS is an important prognosticator for OS/DFS. Sentinel lymph node biopsy delineates prognostic groups in thick melanomas and can impact management. Copyright © 2014 Elsevier Inc. All rights reserved.
Fenske, Timothy S; Ahn, Kwang W; Graff, Tara M; DiGilio, Alyssa; Bashir, Qaiser; Kamble, Rammurti T; Ayala, Ernesto; Bacher, Ulrike; Brammer, Jonathan E; Cairo, Mitchell; Chen, Andy; Chen, Yi-Bin; Chhabra, Saurabh; D'Souza, Anita; Farooq, Umar; Freytes, Cesar; Ganguly, Siddhartha; Hertzberg, Mark; Inwards, David; Jaglowski, Samantha; Kharfan-Dabaja, Mohamed A; Lazarus, Hillard M; Nathan, Sunita; Pawarode, Attaphol; Perales, Miguel-Angel; Reddy, Nishitha; Seo, Sachiko; Sureda, Anna; Smith, Sonali M; Hamadani, Mehdi
2016-07-01
For diffuse large B-cell lymphoma (DLBCL) patients progressing after autologous haematopoietic cell transplantation (autoHCT), allogeneic HCT (alloHCT) is often considered, although limited information is available to guide patient selection. Using the Center for International Blood and Marrow Transplant Research (CIBMTR) database, we identified 503 patients who underwent alloHCT after disease progression/relapse following a prior autoHCT. The 3-year probabilities of non-relapse mortality, progression/relapse, progression-free survival (PFS) and overall survival (OS) were 30, 38, 31 and 37% respectively. Factors associated with inferior PFS on multivariate analysis included Karnofsky performance status (KPS) <80, chemoresistance, autoHCT to alloHCT interval <1-year and myeloablative conditioning. Factors associated with worse OS on multivariate analysis included KPS<80, chemoresistance and myeloablative conditioning. Three adverse prognostic factors were used to construct a prognostic model for PFS, including KPS<80 (4 points), autoHCT to alloHCT interval <1-year (2 points) and chemoresistant disease at alloHCT (5 points). This CIBMTR prognostic model classified patients into four groups: low-risk (0 points), intermediate-risk (2-5 points), high-risk (6-9 points) or very high-risk (11 points), predicting 3-year PFS of 40, 32, 11 and 6%, respectively, with 3-year OS probabilities of 43, 39, 19 and 11% respectively. In conclusion, the CIBMTR prognostic model identifies a subgroup of DLBCL patients experiencing long-term survival with alloHCT after a failed prior autoHCT. © 2016 John Wiley & Sons Ltd.
Nsengimana, Jérémie; Laye, Jon; Filia, Anastasia; Walker, Christy; Jewell, Rosalyn; Van den Oord, Joost J; Wolter, Pascal; Patel, Poulam; Sucker, Antje; Schadendorf, Dirk; Jönsson, Göran B; Bishop, D Timothy; Newton-Bishop, Julia
2015-05-10
Development and validation of robust molecular biomarkers has so far been limited in melanoma research. In this paper we used a large population-based cohort to replicate two published gene signatures for melanoma classification. We assessed the signatures prognostic value and explored their biological significance by correlating them with factors known to be associated with survival (vitamin D) or etiological routes (nevi, sun sensitivity and telomere length). Genomewide microarray gene expressions were profiled in 300 archived tumors (224 primaries, 76 secondaries). The two gene signatures classified up to 96% of our samples and showed strong correlation with melanoma specific survival (P=3 x 10(-4)), Breslow thickness (P=5 x 10(-10)), ulceration (P=9.x10-8) and mitotic rate (P=3 x 10(-7)), adding prognostic value over AJCC stage (adjusted hazard ratio 1.79, 95%CI 1.13-2.83), as previously reported. Furthermore, molecular subtypes were associated with season-adjusted serum vitamin D at diagnosis (P=0.04) and genetically predicted telomere length (P=0.03). Specifically, molecular high-grade tumors were more frequent in patients with lower vitamin D levels whereas high immune tumors came from patients with predicted shorter telomeres. Our data confirm the utility of molecular biomarkers in melanoma prognostic estimation using tiny archived specimens and shed light on biological mechanisms likely to impact on cancer initiation and progression.
The Prognostic Nutritional Index Predicts Survival and Identifies Aggressiveness of Gastric Cancer.
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.
Mao, Yihao; Feng, Qingyang; Zheng, Peng; Yang, Liangliang; Zhu, Dexiang; Chang, Wenju; Ji, Meiling; He, Guodong; Xu, Jianmin
2018-06-06
The role of mast cells (MCs) in colorectal cancer (CRC) progression was controversial. Thus, this study was designed to evaluate the prognostic value of MCs as well as their correlation with immune microenvironment. A retrospective cohort of CRC patients of stage I-IV was enrolled in this study. 854 consecutive patients were divided into training set (427 patients) and validation set (427 patients) randomly. The findings were further validated in a GEO cohort, GSE39582 (556 patients). The mast cell density (MCD) was measured by immunohistochemical staining of tryptase or by CIBERSORT algorithm. Low MCD predicted prolonged overall survival (OS) in training and validation set. Moreover, MCD was identified as an independent prognostic indicator in both sets. Better stratification for CRC prognosis can be achieved by building a MCD based nomogram. The prognostic role of MCD was further validated in GSE39582. In addition, MCD predicted improved survival in stage II and III CRC patients receiving adjuvant chemotherapy (ACT). Multiple immune pathways were enriched in low MCD group while cytokines/chemokines promoting anti-tumor immunity were highly expressed in such group. Furthermore, MCD was negatively correlated with CD8+ T cells infiltration. In conclusion, MCD was identified as an independent prognostic factor, as well as a potential biomarker for ACT benefit in stage II and III CRC. Better stratification of CRC prognosis could be achieved by building a MCD based nomogram. Moreover, immunoactivation in low MCD tumors may contributed to improved prognosis. This article is protected by copyright. All rights reserved. © 2018 UICC.
Prognostic significance of β2-adrenergic receptor expression in malignant melanoma.
Shimizu, Akira; Kaira, Kyoichi; Mori, Keita; Kato, Madoka; Shimizu, Kimihiro; Yasuda, Masahito; Takahashi, Ayumi; Oyama, Tetsunari; Asao, Takayuki; Ishikawa, Osamu
2016-05-01
Recent studies cite β2-adrenergic receptor (β2AR) antagonists as novel therapeutic agents for melanoma, as they may reduce the disease progression. The β2AR has shown to be expressed in malignant melanoma. However, it remains unclear whether the β2AR expression has a clinical and pathological significance in patients with cutaneous malignant melanoma. We herein conducted a clinicopathological study to investigate the protein expression of β2AR in malignant melanoma of the skin and its prognostic significance. One hundred thirty-three patients with surgically resected cutaneous malignant melanoma were evaluated. Tumor sections were stained by immunohistochemistry for β2AR, Ki-67, the microvessel density (MVD) determined by CD34, and p53. β2AR was highly expressed in 44.4 % (59 out of 133) of the patients. The expression of β2AR was significantly associated with the tumor thickness, ulceration, T factor, N factor, disease stage, tumor size, cell proliferation (Ki-67), and MVD (CD34). Using Spearman's rank test, the β2AR expression was correlated with Ki-67 (r = 0.278; 95 % CI, 0.108 to 0.432; P = 0.001), CD34 (r = 0.445; 95 %CI, 0.293 to 0.575; P < 0.001), and the tumor size (r = 0.226; 95 % CI, 0.053 to 0.386; P = 0.008). Using a univariate analysis, the tumor thickness, ulceration, disease stage, β2AR, Ki-67, and CD34 had a significant relationship with the overall and progression-free survivals. A multivariable analysis confirmed that β2AR was an independent prognostic factor for predicting a poor overall survival (HR 1.730; 95 % CI 1.221-2.515) and progression-free survival (HR 1.576; 95 % CI 1.176-2.143) of malignant melanoma of the skin. β2AR can serve as a promising prognostic factor for predicting a worse outcome after surgical treatment and may play an important role in the development and aggressiveness of malignant melanoma.
Vermaat, Joost S; Gerritse, Frank L; van der Veldt, Astrid A; Roessingh, Wijnand M; Niers, Tatjana M; Oosting, Sjoukje F; Sleijfer, Stefan; Roodhart, Jeanine M; Beijnen, Jos H; Schellens, Jan H; Gietema, Jourik A; Boven, Epie; Richel, Dick J; Haanen, John B; Voest, Emile E
2012-10-01
We recently identified apolipoprotein A2 (ApoA2) and serum amyloid α (SAA) as independent prognosticators in metastatic renal cell carcinoma (mRCC) patients, thereby improving the accuracy of the Memorial-Sloan Kettering Cancer Center (MSKCC) model. Validate these results prospectively in a separate cohort of mRCC patients treated with tyrosine kinase inhibitors (TKIs). For training we used 114 interferon-treated mRCC patients (inclusion 2001-2006). For validation we studied 151 TKI-treated mRCC patients (inclusion 2003-2009). Using Cox proportional hazards regression analysis, SAA and ApoA2 were associated with progression-free survival (PFS) and overall survival (OS). In 72 TKI-treated patients, SAA levels were analyzed longitudinally as a potential early marker for treatment effect. Baseline ApoA2 and SAA levels significantly predicted PFS and OS in the training and validation cohorts. Multivariate analysis identified SAA in both separate patient sets as a robust and independent prognosticator for PFS and OS. In contrast to our previous findings, ApoA2 interacted with SAA in the validation cohort and did not contribute to a better predictive accuracy than SAA alone and was therefore excluded from further analysis. According to the tertiles of SAA levels, patients were categorized in three risk groups, demonstrating accurate risk prognostication. SAA as a single biomarker showed equal prognostic accuracy when compared with the multifactorial MSKCC risk mode. Using receiver operating characteristic analysis, SAA levels >71 ng/ml were designated as the optimal cut-off value in the training cohort, which was confirmed for its significant sensitivity and specificity in the validation cohort. Applying SAA >71 ng/ml as an additional risk factor significantly improved the predictive accuracy of the MSKCC model in both independent cohorts. Changes in SAA levels after 6-8 wk of TKI treatment had no value in predicting treatment outcome. SAA but not ApoA2 was shown to be a robust and independent prognosticator for PFS and OS in mRCC patients. When incorporated in the MSKCC model, SAA showed additional prognostic value for patient management. Copyright © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.
Abbreviation of the Follow-Up NIH Stroke Scale Using Factor Analysis
Raza, Syed Ali; Frankel, Michael R.; Rangaraju, Srikant
2017-01-01
Background The NIH Stroke Scale (NIHSS) is a 15-item measure of stroke-related neurologic deficits that, when measured at 24 h, is highly predictive of long-term functional outcome. We hypothesized that a simplified 24-h scale that incorporates the most predictive components of the NIHSS can retain prognostic accuracy and have improved interrater reliability. Methods In a post hoc analysis of the Interventional Management of Stroke-3 (IMS-3) trial, we performed principal component (PC) analysis to resolve the 24-h NIHSS into PCs. In the PCs that explained the largest proportions of variance, key variables were identified. Using these key variables, the prognostic accuracies (area under the curve [AUC]) for good outcome (3-month modified Rankin Scale [mRS] 0–2) and poor outcome (mRS 5–6) of various abbreviated NIHSS iterations were compared with the total 24-h NIHSS. The results were validated in the NINDS intravenous tissue plasminogen activator (NINDS-TPA) study cohort. Based on previously published data, interrater reliability of the abbreviated 24-h NIHSS (aNIHSS) was compared to the total 24-h NIHSS. Results In 545 IMS-3 participants, 2 PCs explained 60.8% of variance in the 24-h NIHSS. The key variables in PC1 included neglect, arm and leg weakness; while PC2 included level-of-consciousness (LOC) questions, LOC commands, and aphasia. A 3-variable aNIHSS (aphasia, neglect, arm weakness) retained excellent prognostic accuracy for good outcome (AUC = 0.90) as compared to the total 24-h NIHSS (AUC = 0.91), and it was more predictive (p < 0.001) than the baseline NIHSS (AUC = 0.73). The prognostic accuracy of the aNIHSS for good outcome was validated in the NINDS-TPA trial cohort (aNIHSS: AUC = 0.89 vs. total 24-h NIHSS: 0.92). An aNIHSS >9 predicted very poor outcomes (mRS 0–2: 0%, mRS 4–6: 98.5%). The estimated interrater reliability of the aNIHSS was higher than that of the total 24-h NIHSS across 6 published datasets (mean weighted kappa 0.80 vs. 0.73, p < 0.001). Conclusions At 24 h following ischemic stroke, aphasia, neglect, and arm weakness are the most prognostically relevant neurologic findings. The aNIHSS appears to have excellent prognostic accuracy with higher reliability and may be clinically useful. PMID:28968607
Real-Time Prognostics of a Rotary Valve Actuator
NASA Technical Reports Server (NTRS)
Daigle, Matthew
2015-01-01
Valves are used in many domains and often have system-critical functions. As such, it is important to monitor the health of valves and their actuators and predict remaining useful life. In this work, we develop a model-based prognostics approach for a rotary valve actuator. Due to limited observability of the component with multiple failure modes, a lumped damage approach is proposed for estimation and prediction of damage progression. In order to support the goal of real-time prognostics, an approach to prediction is developed that does not require online simulation to compute remaining life, rather, a function mapping the damage state to remaining useful life is found offline so that predictions can be made quickly online with a single function evaluation. Simulation results demonstrate the overall methodology, validating the lumped damage approach and demonstrating real-time prognostics.
Major prognostic role of Ki67 in localized adrenocortical carcinoma after complete resection.
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.
Heymans, Martijn W; Ford, Jon J; McMeeken, Joan M; Chan, Alexander; de Vet, Henrica C W; van Mechelen, Willem
2007-09-01
Successful management of workers on sick leave due to low back pain by the general physician and physiotherapist depends on reliable prognostic information on the course of low back pain and work resumption. Retrospective cohort study in 194 patients who were compensated because of chronic low back pain and who were treated by a physiotherapy functional restoration program. Patient-reported and clinician based prognostic indicators were assessed at baseline before patients entered the functional restoration program. We investigated the predictive value of these indicators on work status at 6 months. Relationships were studied using logistic regression analysis in a 2-step bootstrap modelling approach and a nomogram was developed. Discrimination and calibration of the nomogram was evaluated internally and the explained variation of the nomogram calculated. Seventy percent of workers were back to work at 6 months. We found that including duration of complaints, functional disability, disc herniation and fear avoidance beliefs resulted in the "best" prognostic model. All these factors delayed work resumption. This model was used to construct a nomogram. The explained variation of the nomogram was 23.7%. Discrimination was estimated by the area under the receiver operating characteristic curve and was 0.76 and for calibration we used the slope estimate that was 0.91. The positive predictive values of the nomogram at different cut-off levels of predicted probability were good. Knowledge of the predictive value of these indicators by physicians and physiotherapists will help to identify subgroups of patients and will thus enhance clinical decision-making.
Singhal, Neha; Praveen, V. P.; Bhavani, Nisha; Menon, Arun S.; Menon, Usha; Abraham, Nithya; Kumar, Harish; JayKumar, R. V.; Nair, Vasantha; Sundaram, Shanmugha; Sundaram, Padma
2016-01-01
Context: Most of the information on remission related factors in Grave's disease are derived from Western literature. It is likely that there may be additional prognostic factors and differences in the postdrug treatment course of Grave's disease in India. Aim: To study factors which predict remission/relapse in Grave's disease patients from South India. Also to establish if technetium (Tc) uptake has a role in predicting remission. Subjects and Methods: Records of 174 patients with clinical, biochemical, and scintigraphic criteria consistent with Grave's disease, seen in our Institution between January 2006 and 2014 were analyzed. Patient factors, drug-related factors, Tc-99m uptake and other clinical factors were compared between the remission and nonremission groups. Statistical Analysis Used: Mann–Whitney U-test and Chi-square tests were used when appropriate to compare the groups. Results: Fifty-seven (32.7%) patients attained remission after at least 1 year of thionamide therapy. Of these, 11 (19.2%) patients relapsed within 1 year. Age, gender, goiter, and presence of extrathyroidal manifestations were not associated with remission. Higher values of Tc uptake were positively associated with remission (P- 0.02). Time to achievement of normal thyroid function and composite dose: Time scores were significantly associated with remission (P - 0.05 and P - 0.01, respectively). Patients with lower FT4 at presentation had a higher chance of remission (P - 0.01). The relapse rates were lower than previously reported in the literature. A higher Tc uptake was found to be significantly associated with relapse also (P - 0.009). Conclusion: The prognostic factors associated with remission in Graves's disease in this South Indian study are not the same as that reported in Western literature. Tc scintigraphy may have an additional role in identifying people who are likely to undergo remission and thus predict the outcome of Grave's disease. PMID:27042408
Singhal, Neha; Praveen, V P; Bhavani, Nisha; Menon, Arun S; Menon, Usha; Abraham, Nithya; Kumar, Harish; JayKumar, R V; Nair, Vasantha; Sundaram, Shanmugha; Sundaram, Padma
2016-01-01
Most of the information on remission related factors in Grave's disease are derived from Western literature. It is likely that there may be additional prognostic factors and differences in the postdrug treatment course of Grave's disease in India. To study factors which predict remission/relapse in Grave's disease patients from South India. Also to establish if technetium (Tc) uptake has a role in predicting remission. Records of 174 patients with clinical, biochemical, and scintigraphic criteria consistent with Grave's disease, seen in our Institution between January 2006 and 2014 were analyzed. Patient factors, drug-related factors, Tc-99m uptake and other clinical factors were compared between the remission and nonremission groups. Mann-Whitney U-test and Chi-square tests were used when appropriate to compare the groups. Fifty-seven (32.7%) patients attained remission after at least 1 year of thionamide therapy. Of these, 11 (19.2%) patients relapsed within 1 year. Age, gender, goiter, and presence of extrathyroidal manifestations were not associated with remission. Higher values of Tc uptake were positively associated with remission (P- 0.02). Time to achievement of normal thyroid function and composite dose: Time scores were significantly associated with remission (P - 0.05 and P - 0.01, respectively). Patients with lower FT4 at presentation had a higher chance of remission (P - 0.01). The relapse rates were lower than previously reported in the literature. A higher Tc uptake was found to be significantly associated with relapse also (P - 0.009). The prognostic factors associated with remission in Graves's disease in this South Indian study are not the same as that reported in Western literature. Tc scintigraphy may have an additional role in identifying people who are likely to undergo remission and thus predict the outcome of Grave's disease.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Sperduto, Paul W., E-mail: psperduto@mropa.co; Chao, Samuel T.; Sneed, Penny K.
2010-07-01
Purpose: Controversy endures regarding the optimal treatment of patients with brain metastases (BMs). Debate persists, despite many randomized trials, perhaps because BM patients are a heterogeneous population. The purpose of the present study was to identify significant diagnosis-specific prognostic factors and indexes (Diagnosis-Specific Graded Prognostic Assessment [DS-GPA]). Methods and Materials: A retrospective database of 5,067 patients treated for BMs between 1985 and 2007 was generated from 11 institutions. After exclusion of the patients with recurrent BMs or incomplete data, 4,259 patients with newly diagnosed BMs remained eligible for analysis. Univariate and multivariate analyses of the prognostic factors and outcomes bymore » primary site and treatment were performed. The significant prognostic factors were determined and used to define the DS-GPA prognostic indexes. The DS-GPA scores were calculated and correlated with the outcomes, stratified by diagnosis and treatment. Results: The significant prognostic factors varied by diagnosis. For non-small-cell lung cancer and small-cell lung cancer, the significant prognostic factors were Karnofsky performance status, age, presence of extracranial metastases, and number of BMs, confirming the original GPA for these diagnoses. For melanoma and renal cell cancer, the significant prognostic factors were Karnofsky performance status and the number of BMs. For breast and gastrointestinal cancer, the only significant prognostic factor was the Karnofsky performance status. Two new DS-GPA indexes were thus designed for breast/gastrointestinal cancer and melanoma/renal cell carcinoma. The median survival by GPA score, diagnosis, and treatment were determined. Conclusion: The prognostic factors for BM patients varied by diagnosis. The original GPA was confirmed for non-small-cell lung cancer and small-cell lung cancer. New DS-GPA indexes were determined for other histologic types and correlated with the outcome, and statistical separation between the groups was confirmed. These data should be considered in the design of future randomized trials and in clinical decision-making.« less
Paxton, Dolcie; Pauling, John D
2018-02-14
Nailfold capillaroscopy (NC) is an important diagnostic tool in systemic sclerosis (SSc). Confirmation of NC as a prognostic factor could facilitate earlier intervention and slow disease progression in SSc. We undertook a systematic literature review to evaluate the prognostic value of NC in predicting SSc disease progression. Standardised searches of EMBASE and MEDLINE were undertaken to identify longitudinal studies of adult subjects with SSc reporting the prognostic value of NC for any aspect of disease progression and/or survival. Non-English, non-original research, animal studies, non-adult studies and non-full length reports were excluded from the analysis (PROSPERO 2017:CRD42017071719). Wide heterogeneity in study design, prognostic factor measurement and study outcomes necessitated a qualitative data synthesis. The "QUality In Prognosis Studies" (QUIPS) risk-of-bias tool was used to assess study quality. Study selection, data extraction and risk-of-bias assessment were each undertaken independently by 2 reviewers and consensus reached where necessary. Of 942 retrieved articles, 18 studies fulfilled the inclusion criteria. The majority of studies (17/18, 94%) reported positive associations between baseline NC appearances (using a variety of qualitative, semi-quantitative and quantitative NC endpoints) and clinical outcomes including digital ulcer (DU) occurrence/healing, survival, disease progression (using domains of Medsger disease severity scale), calcinosis, skin progression, pulmonary arterial hypertension (PAH), and/or a composite analysis of "cardiovascular events". Application of the QUIPS tool identified a moderate-high risk of potential bias in 6/18 studies for study participation, 3/18 studies for study attrition, 10/18 for prognostic factor measurement, 5/18 for outcome measurement, 13/18 for confounders and 13/18 for statistical analyses. Study quality limited the strength of the conclusions drawn from these studies. The most important source of potential bias across the studies was insufficient adjustment for potential confounders; such as existing DU disease in studies evaluating future DU occurrence. Recent work suggests NC evolution is an important predictor of disease progression in SSc. High levels of potential bias relating to study confounding and statistical analysis make it difficult to draw conclusions regarding the prognostic role of NC in SSc. There is strong evidence supporting an association between NC abnormalities (particularly capillary loss) and disease severity (particularly vascular manifestations such as DU, calcinosis and PAH). Evolution of NC appearances may represent a more important predictor of disease progression which could have important implications for the future use of NC in the routine longitudinal assessment and management of SSc. Copyright © 2018 Elsevier Inc. All rights reserved.
HASEGAWA, SHINICHIRO; EGUCHI, HIDETOSHI; TOMOKUNI, AKIRA; TOMIMARU, YOSHITO; ASAOKA, TADAFUMI; WADA, HIROSHI; HAMA, NAOKI; KAWAMOTO, KOICHI; KOBAYASHI, SHOGO; MARUBASHI, SHIGERU; KONNNO, MASAMITSU; ISHII, HIDESHI; MORI, MASAKI; DOKI, YUICHIRO; NAGANO, HIROAKI
2016-01-01
An elevated neutrophil to lymphocyte ratio (NLR) has been reported to be associated with the pathological response to neoadjuvant therapies in numerous types of cancer. The aim of the current study was to clarify the association between pre-treatment NLR and the pathological response to preoperative chemoradiotherapy in pancreatic cancer patients. This retrospective analysis included data from 56 consecutive patients whose tumors were completely surgically resected. All patients received preoperative therapy, consisting of gemcitabine-based chemotherapy (alone or in combination with S-1) combined with 40 or 50.4 Gy irradiation, prior to surgery. Predictive factors, including NLR, platelet to lymphocyte ratio (PLR), modified Glasgow prognostic score and prognostic nutrition index, were measured prior to treatment. A comparison was made between those who responded well pathologically (good response group, Evans classification IIb/III) and those with a poor response (Evans I/IIa). NLR was determined to be significantly higher in the poor response group. Multivariate analysis identified an elevated NLR as an independent risk factor for the poor pathological response [odds ratio (OR), 5.35; P=0.0257]. The pre-treatment NLR (≥2.2/<2.2) was found to be a statistically significant predictive indicator of pathological response (P=0.00699). The results demonstrate that pre-treatment NLR may be a useful predictive marker for the pathological response to preoperative therapy in pancreatic cancer patients. PMID:26893780
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.
Lin, Ching-Yih; Lee, Ying-En; Tian, Yu-Feng; Sun, Ding-Ping; Sheu, Ming-Jen; Lin, Chen-Yi; Li, Chien-Feng; Lee, Sung-Wei; Lin, Li-Ching; Chang, I-Wei; Wang, Chieh-Tien; He, Hong-Lin
2017-01-01
Background: Numerous transmembrane receptor tyrosine kinase pathways have been found to play an important role in tumor progression in some cancers. This study was aimed to evaluate the clinical impact of Eph receptor A4 (EphA4) in patients with rectal cancer treated with neoadjuvant concurrent chemoradiotherapy (CCRT) combined with mesorectal excision, with special emphasis on tumor regression. Methods: Analysis of the publicly available expression profiling dataset of rectal cancer disclosed that EphA4 was the top-ranking, significantly upregulated, transmembrane receptor tyrosine kinase pathway-associated gene in the non-responders to CCRT, compared with the responders. Immunohistochemical study was conducted to assess the EphA4 expression in pre-treatment biopsy specimens from 172 rectal cancer patients without distant metastasis. The relationships between EphA4 expression and various clinicopathological factors or survival were statistically analyzed. Results: EphA4 expression was significantly associated with vascular invasion ( P =0.015), post-treatment depth of tumor invasion ( P =0.006), pre-treatment and post-treatment lymph node metastasis ( P =0.004 and P =0.011, respectively). More importantly, high EphA4 expression was significantly predictive for lesser degree of tumor regression after CCRT ( P =0.031). At univariate analysis, high EphA4 expression was a negative prognosticator for disease-specific survival ( P =0.0009) and metastasis-free survival ( P =0.0001). At multivariate analysis, high expression of EphA4 still served as an independent adverse prognostic factor for disease-specific survival (HR, 2.528; 95% CI, 1.131-5.651; P =0.024) and metastasis-free survival (HR, 3.908; 95% CI, 1.590-9.601; P =0.003). Conclusion: High expression of EphA4 predicted lesser degree of tumor regression after CCRT and served as an independent negative prognostic factor in patients with rectal cancer.
Honda, Shohei; Haruta, Masayuki; Sugawara, Waka; Sasaki, Fumiaki; Ohira, Miki; Matsunaga, Tadashi; Yamaoka, Hiroaki; Horie, Hiroshi; Ohnuma, Naomi; Nakagawara, Akira; Hiyama, Eiso; Todo, Satoru; Kaneko, Yasuhiko
2008-09-01
Despite the progress of therapy, outcomes of advanced hepatoblastoma patients who are refractory to standard preoperative chemotherapy remain unsatisfactory. To improve the mortality rate, novel prognostic markers are needed for better therapy planning. We examined the methylation status of 13 candidate tumor suppressor genes in 20 hepatoblastoma tumors by conventional methylation-specific PCR (MSP) and found hypermethylation in 3 of the 13 genes. We analyzed the methylation status of these 3 genes (RASSF1A, SOCS1 and CASP8) in 97 tumors and found hypermethylation in 30.9, 33.0 and 15.5%, respectively. Univariate analysis showed that only the methylation status of RASSF1A but not the other 2 genes predicted the outcome, and multivariate analysis showed a weak contribution of RASSF1A methylation to overall survival. Using quantitative MSP, we found RASSF1A methylation in 44.3% of the 97 tumors. CTNNB1 mutation was detected in 67.0% of the 97 tumors. While univariate analysis demonstrated RASSF1A methylation, CTNNB1 mutation and other clinicopathological variables as prognostic factors, multivariate analysis identified RASSF1A methylation (p = 0.043; relative risk 9.39) and the disease stage (p = 0.002; relative risk 7.67) but not CTNNB1 mutation as independent prognostic factors. In survival analysis of 33 patients in stage 3B or 4, patients with unmethylated tumor had better overall survival than those with methylated tumor (p = 0.035). RASSF1A methylation may be a promising molecular-genetic marker to predict the treatment outcome and may be used to stratify patients when clinical trials are carried out.
Feng, Ji-Feng; Huang, Ying; Chen, Qi-Xun
2014-10-01
The prognostic value of inflammation indexes in esophageal cancer was not established. In this study, therefore, both prognostic values of Glasgow prognostic score (GPS) and combination of platelet count and neutrophil lymphocyte ratio (COP-NLR) in patients with esophageal squamous cell carcinoma (ESCC) were investigated and compared. This retrospective study included 375 patients who underwent esophagectomy for ESCC. The cancer-specific survival (CSS) was calculated by the Kaplan-Meier method, and the difference was assessed by the log-rank test. The GPS was calculated as follows: patients with elevated C-reactive protein (> 10 mg/l) and hypoalbuminemia (< 35 g/l) were assigned to GPS2. Patients with one or no abnormal value were assigned to GPS1 or GPS0, respectively. The COP-NLR was calculated as follows: patients with elevated platelet count (> 300 × 10(9)/l) and neutrophil lymphocyte ratio (> 3) were assigned to COP-NLR2. Patients with one or no abnormal value were assigned to COP-NLR1 or COP-NLR0, respectively. The 5-year CSS in patients with GPS0, 1, and 2 was 50.0%, 27.0%, and 12.5%, respectively (P < .001). The 5-year CSS in patients with COP-NLR0, 1, and 2 was 51.8%, 27.0%, and 11.6%, respectively (P < .001). Multivariate analysis showed that both GPS (P = .003) and COP-NLR (P = .003) were significant predictors in such patients. In addition, our study demonstrated a similar hazard ratio (HR) between COP-NLR and GPS (HR = 1.394 vs HR = 1.367). COP-NLR is an independent predictive factor in patients with ESCC. We conclude that COP-NLR predicts survival in ESCC similar to GPS.
A Prognostic Model for One-year Mortality in Patients Requiring Prolonged Mechanical Ventilation
Carson, Shannon S.; Garrett, Joanne; Hanson, Laura C.; Lanier, Joyce; Govert, Joe; Brake, Mary C.; Landucci, Dante L.; Cox, Christopher E.; Carey, Timothy S.
2009-01-01
Objective A measure that identifies patients who are at high risk of mortality after prolonged ventilation will help physicians communicate prognosis to patients or surrogate decision-makers. Our objective was to develop and validate a prognostic model for 1-year mortality in patients ventilated for 21 days or more. Design Prospective cohort study. Setting University-based tertiary care hospital Patients 300 consecutive medical, surgical, and trauma patients requiring mechanical ventilation for at least 21 days were prospectively enrolled. Measurements and Main Results Predictive variables were measured on day 21 of ventilation for the first 200 patients and entered into logistic regression models with 1-year and 3-month mortality as outcomes. Final models were validated using data from 100 subsequent patients. One-year mortality was 51% in the development set and 58% in the validation set. Independent predictors of mortality included requirement for vasopressors, hemodialysis, platelet count ≤150 ×109/L, and age ≥50. Areas under the ROC curve for the development model and validation model were 0.82 (se 0.03) and 0.82 (se 0.05) respectively. The model had sensitivity of 0.42 (se 0.12) and specificity of 0.99 (se 0.01) for identifying patients who had ≥90% risk of death at 1 year. Observed mortality was highly consistent with both 3- and 12-month predicted mortality. These four predictive variables can be used in a simple prognostic score that clearly identifies low risk patients (no risk factors, 15% mortality) and high risk patients (3 or 4 risk factors, 97% mortality). Conclusions Simple clinical variables measured on day 21 of mechanical ventilation can identify patients at highest and lowest risk of death from prolonged ventilation. PMID:18552692
Meany, Holly J; London, Wendy B; Ambros, Peter F; Matthay, Katherine K; Monclair, Tom; Simon, Thorsten; Garaventa, Alberto; Berthold, Frank; Nakagawara, Akira; Cohn, Susan L; Pearson, Andrew D J; Park, Julie R
2014-11-01
International Neuroblastoma Staging System (INSS) Stage 3 neuroblastoma is a heterogeneous disease. Data from the International Neuroblastoma Risk Group (INRG) database were analyzed to define patient and tumor characteristics predictive of outcome. Of 8,800 patients in the INRG database, 1,483 with INSS Stage 3 neuroblastoma and complete follow-up data were analyzed. Secondary analysis was performed in 1,013 patients (68%) with MYCN-non-amplified (NA) tumors. Significant prognostic factors were identified via log-rank test comparisons of survival curves. Multivariable Cox proportional hazards regression model was used to identify factors independently predictive of event-free survival (EFS). Age at diagnosis (P < 0.0001), tumor MYCN status (P < 0.0001), and poorly differentiating/undifferentiated histology (P = 0.03) were independent predictors of EFS. Compared to other Stage 3 subgroups, outcome was inferior for patients ≥ 547 days with MYCN-NA neuroblastoma (P < 0.0001), and within this cohort, serum ferritin ≥ 96 ng/ml was associated with inferior EFS (P = 0.02). For patients <547 days of age with MYCN-NA tumors, serum ferritin levels were prognostic of overall survival (OS) (P = 0.04) and chromosome 11q aberration was prognostic of EFS (P = 0.03). Among patients with INSS Stage 3 neuroblastoma patients, age at diagnosis, MYCN status and histology predict outcome. Patients <547 days of age with MYCN-NA tumors that lack chromosome 11q aberrations or those with serum ferritin <96 ng/ml have excellent prognosis and should be considered for therapy reduction. Prospective clinical trials are needed to identify optimal therapy for those patients ≥ 547 days of age with undifferentiated histology or elevated serum ferritin. © 2014 Wiley Periodicals, Inc.
Han, Donghee; Hartaigh, Bríain Ó; Gransar, Heidi; Lee, Ji Hyun; Rizvi, Asim; Baskaran, Lohendran; Schulman-Marcus, Joshua; Dunning, Allison; Achenbach, Stephan; Al-Mallah, Mouaz H; Berman, Daniel S; Budoff, Matthew J; Cademartiri, Filippo; Maffei, Erica; Callister, Tracy Q; Chinnaiyan, Kavitha; Chow, Benjamin J W; DeLago, Augustin; Hadamitzky, Martin; Hausleiter, Joerg; Kaufmann, Philipp A; Raff, Gilbert; Shaw, Leslee J; Villines, Todd C; Kim, Yong-Jin; Leipsic, Jonathon; Feuchtner, Gudrun; Cury, Ricardo C; Pontone, Gianluca; Andreini, Daniele; Marques, Hugo; Rubinshtein, Ronen; Hindoyan, Niree; Jones, Erica C; Gomez, Millie; Lin, Fay Y; Chang, Hyuk-Jae; Min, James K
2018-01-01
Abstract Aims Coronary computed tomography angiography (CCTA) and coronary artery calcium score (CACS) have prognostic value for coronary artery disease (CAD) events beyond traditional risk assessment. Age is a risk factor with very high weight and little is known regarding the incremental value of CCTA over CAC for predicting cardiac events in older adults. Methods and results Of 27 125 individuals undergoing CCTA, a total of 3145 asymptomatic adults were identified. This study sample was categorized according to tertiles of age (cut-off points: 52 and 62 years). CAD severity was classified as 0, 1–49, and ≥50% maximal stenosis in CCTA, and further categorized according to number of vessels ≥50% stenosis. The Framingham 10-year risk score (FRS) and CACS were employed as major covariates. Major adverse cardiovascular events (MACE) were defined as a composite of all-cause death or non-fatal MI. During a median follow-up of 26 months (interquartile range: 18–41 months), 59 (1.9%) MACE occurred. For patients in the top age tertile, CCTA improved discrimination beyond a model included FRS and CACS (C-statistic: 0.75 vs. 0.70, P-value = 0.015). Likewise, the addition of CCTA improved category-free net reclassification (cNRI) of MACE in patients within the highest age tertile (e.g. cNRI = 0.75; proportion of events/non-events reclassified were 50 and 25%, respectively; P-value <0.05, all). CCTA displayed no incremental benefit beyond FRS and CACS for prediction of MACE in the lower age tertiles. Conclusion CCTA provides added prognostic value beyond cardiac risk factors and CACS for the prediction of MACE in asymptomatic older adults. PMID:28977374
Lin, Cheng-Yi; Lin, Ching-Yih; Chang, I-Wei; Sheu, Ming-Jen; Li, Chien-Feng; Lee, Sung-Wei; Lin, Li-Ching; Lee, Ying-En; He, Hong-Lin
2015-01-01
Neoadjuvant concurrent chemoradiotherapy (CCRT) followed by surgery is the mainstay of treatment for locally advanced rectal cancer. Several heparin-binding associated proteins have been reported to play a critical role in cancer progression. However, the clinical relevancies of such proteins and their associations with CCRT response in rectal cancer have not yet to be fully elucidated. The analysis of a public transcriptome of rectal cancer indicated that thrombospondin 2 (THBS2) is a predictive factor for CCRT response. Immunohistochemical analyses were conducted to evaluate the expression of THBS2 in pretreatment biopsy specimens from rectal cancer patients without distant metastasis. Furthermore, the relationships between THBS2 expression and various clinicopathological factors or survival were analyzed. Low expression of THBS2 was significantly associated with advanced pretreatment tumor (P<0.001) and nodal status (P=0.004), post-treatment tumor (P<0.001) and nodal status (P<0.001), increased vascular invasion (P=0.003), increased perineural invasion (P=0.023) and inferior tumor regression grade (P=0.015). In univariate analysis, low THBS2 expression predicted worse outcomes for disease-free survival, local recurrence-free survival and metastasis-free survival (all P<0.001). In multivariate analysis, low expression of THBS2 still served as a negative prognostic factor for disease-free survival (Hazard ratio=3.057, P=0.002) and metastasis-free survival (Hazard ratio=3.362, P=0.012). Low THBS2 expression was correlated with advanced disease status and low tumor regression after preoperative CCRT and that it acted as an independent negative prognostic factor in rectal cancer. THBS2 may represent a predictive biomarker for CCRT response in rectal cancer.
Features and prognostic factors for elderly with acute poisoning in the emergency department.
Hu, Yu-Hui; Chou, Hsiu-Ling; Lu, Wen-Hua; Huang, Hsien-Hao; Yang, Cheng-Chang; Yen, David H T; Kao, Wei-Fong; Deng, Jou-Fan; Huang, Chun-I
2010-02-01
Elderly persons with acute poisoning in the emergency department (ED) and prognostic factors of outcomes have not been well addressed in previous research. This study aimed to investigate the characteristics of elderly patients with acute poisoning visiting the ED, and to identify the possible predictive factors of mortality. Patients aged > or = 65 years with acute poisoning who visited the ED in Taipei Veterans General Hospital from January 1, 2006 through to September 30, 2008 were enrolled in the study. We collected demographic information on underlying diseases, initial presentations, causes and toxic substances, complications, dispositions, and outcomes. Analyses were conducted among different groups categorized according to age, suicide attempt, and outcome. Multiple logistic regression was applied to identify possible predictive clinical factors influencing mortality in the elderly with acute poisoning. A total of 250 patients were enrolled in the study, with a mean age of 77 years and male predominance. The most common cause of intoxication was unintentional poisoning. Medication accounted for 57.6% of poisonous substances, of which benzodiazepine was the most common drug, followed by warfarin. The overall mortality rate was 9.6%. The average length of stay in the ED increased significantly in the old (65-74 years), very old (75-84 years) and extremely old (> or = 85 years) groups. Suicide attempt patients experienced more complications including respiratory failure, aspiration pneumonia, hypotension and mortality. Three clinical predictive factors of mortality were identified: herbicide poisoning, hypotension and respiratory failure upon presentation. Our results demonstrated that elderly patients with acute poisoning had a mortality rate of 9.6%. Suicide attempts resulted in more serious complications. The risk factors for mortality were herbicide intoxication, hypotension and respiratory failure. Copyright 2010 Elsevier. Published by Elsevier B.V. All rights reserved.
Bütof, Rebecca; Hofheinz, Frank; Zöphel, Klaus; Stadelmann, Tobias; Schmollack, Julia; Jentsch, Christina; Löck, Steffen; Kotzerke, Jörg; Baumann, Michael; van den Hoff, Jörg
2015-08-01
Despite ongoing efforts to develop new treatment options, the prognosis for patients with inoperable esophageal carcinoma is still poor and the reliability of individual therapy outcome prediction based on clinical parameters is not convincing. The aim of this work was to investigate whether PET can provide independent prognostic information in such a patient group and whether the tumor-to-blood standardized uptake ratio (SUR) can improve the prognostic value of tracer uptake values. (18)F-FDG PET/CT was performed in 130 consecutive patients (mean age ± SD, 63 ± 11 y; 113 men, 17 women) with newly diagnosed esophageal cancer before definitive radiochemotherapy. In the PET images, the metabolically active tumor volume (MTV) of the primary tumor was delineated with an adaptive threshold method. The blood standardized uptake value (SUV) was determined by manually delineating the aorta in the low-dose CT. SUR values were computed as the ratio of tumor SUV and blood SUV. Uptake values were scan-time-corrected to 60 min after injection. Univariate Cox regression and Kaplan-Meier analysis with respect to overall survival (OS), distant metastases-free survival (DM), and locoregional tumor control (LRC) was performed. Additionally, a multivariate Cox regression including clinically relevant parameters was performed. In multivariate Cox regression with respect to OS, including T stage, N stage, and smoking state, MTV- and SUR-based parameters were significant prognostic factors for OS with similar effect size. Multivariate analysis with respect to DM revealed smoking state, MTV, and all SUR-based parameters as significant prognostic factors. The highest hazard ratios (HRs) were found for scan-time-corrected maximum SUR (HR = 3.9) and mean SUR (HR = 4.4). None of the PET parameters was associated with LRC. Univariate Cox regression with respect to LRC revealed a significant effect only for N stage greater than 0 (P = 0.048). PET provides independent prognostic information for OS and DM but not for LRC in patients with locally advanced esophageal carcinoma treated with definitive radiochemotherapy in addition to clinical parameters. Among the investigated uptake-based parameters, only SUR was an independent prognostic factor for OS and DM. These results suggest that the prognostic value of tracer uptake can be improved when characterized by SUR instead of SUV. Further investigations are required to confirm these preliminary results. © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.
Abe, Naoyuki; Miura, Takashi; Miyashita, Yusuke; Hashizume, Naoto; Ebisawa, Soichiro; Motoki, Hirohiko; Tsujimura, Takuya; Ishihara, Takayuki; Uematsu, Masaaki; Katagiri, Toshio; Ishihara, Ryuma; Tosaka, Atsushi; Ikeda, Uichi
2017-04-01
The admission shock index (SI) enables prediction of short-term prognosis. This study investigated the prognostic implications of admission SI for predicting long-term prognoses for acute myocardial infarction (AMI). The participants were 680 patients with AMI who received percutaneous coronary intervention. Shock index is the ratio of heart rate and systolic blood pressure. Patients were classified as admission SI <0.66 (normal) and ≥0.66 (elevated; 75th percentile). The end point was 5-year major adverse cardiac events (MACEs). Elevated admission SI was seen in 176 patients. Peak creatine kinase levels were significantly higher and left ventricular ejection fraction was lower in the elevated SI group, which had a worse MACEs. In multivariate Cox regression analysis, SI ≥0.66 was a risk factor for MACE. Elevated admission SI was associated with poorer long-term prognosis.
Fusar-Poli, P; Schultze-Lutter, F
2016-02-01
Prediction of psychosis in patients at clinical high risk (CHR) has become a mainstream focus of clinical and research interest worldwide. When using CHR instruments for clinical purposes, the predicted outcome is but only a probability; and, consequently, any therapeutic action following the assessment is based on probabilistic prognostic reasoning. Yet, probabilistic reasoning makes considerable demands on the clinicians. We provide here a scholarly practical guide summarising the key concepts to support clinicians with probabilistic prognostic reasoning in the CHR state. We review risk or cumulative incidence of psychosis in, person-time rate of psychosis, Kaplan-Meier estimates of psychosis risk, measures of prognostic accuracy, sensitivity and specificity in receiver operator characteristic curves, positive and negative predictive values, Bayes' theorem, likelihood ratios, potentials and limits of real-life applications of prognostic probabilistic reasoning in the CHR state. Understanding basic measures used for prognostic probabilistic reasoning is a prerequisite for successfully implementing the early detection and prevention of psychosis in clinical practice. Future refinement of these measures for CHR patients may actually influence risk management, especially as regards initiating or withholding treatment. 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/
Su, Chunxia; Xu, Ying; Li, Xuefei; Ren, Shengxiang; Zhao, Chao; Hou, Likun; Ye, Zhiwei; Zhou, Caicun
2015-01-01
CD133 and cancer-testis antigens (CTAs) may be potential predicted markers of adjuvant chemotherapy or immune therapy, and they may be the independent prognostic factor of NSCLC. Nowadays, there is still no predictive biomarker identified for the use of adjuvant chemotherapy in non-small cell lung cancer (NSCLC) patients. To clarify the role of CD133 and CTAs as a predictive marker for adjuvant chemotherapy or prognostic factors of overall survival, we performed a retrospective study in 159 stage Ib-IIIA NSCLC patients receiving adjuvant chemotherapy or observe from April 2003 to March 2004 in our institute. Clinical data and gene anaylisis results were collected, while CD133 and three CTAs (MAGE-A4, NY-ESO-1, MAGE-A10) were determined according to their monoclonal antibodies such as CD133, 57B, D8.38 and 3GA11 by immunohistochemistry. All CTAs were more frequently expressed in squamous cell carcinoma (SCC) (50.0%, 26.9%, 34.6%) than in adenocarcinoma (16.2%, 16.2%, 16.2%). CD133 was more frequently found in patients with adenocarcinoma (P=0.044). Negative expression of CD133 was associated with a significantly longer overall survival compared to positive expression of CD133 (62.5 vs. 48.5 months, P=0.035). When combined with MAGEA4, NY-ESO-1or MAGE-A10, patients' OS showed significantly difference among different combination. (CD133-MAGEA4-/CD133-MAGEA4+/CD133+MAGEA4-/CD133+MAGEA4+: 65.6 months vs.51.5 months vs.32.2 months vs.19.8 months, P=0.000, CD133-NY-ESO-1-/ CD133+NY-ESO-1-/CD133-NY-ESO-1+/ CD133+NY-ESO-1+: 57.8 months vs. 55.7 months vs. 44.6 months vs. 28.5 months, P=0.000, CD133-MAGEA10-/CD133+ MAGEA10-/CD133-MAGEA10-/CD133+MAGEA10+: 66.2 months vs. 57.2 months vs. 48.8 months vs. 41.4 months, P=0.001). There is no difference between patients received adjuvant chemotherapy or not, but subgroup analysis showed that the patients with CD133+NY-ESO-1+ expression who received chemotherapy will survive longer than not receive adjuvant chemotherapy (received vs. not received, 52.1 vs. 27.1 months, P=0.020). In the subgroup with EGFR mutation/ALK translocation/Ros1 translocation/Ret fusion, the trend remained but without a statistically significant difference. Multivariate COX regression analysis showed that stage, CD133, CD133-MAGEA4- and CD133-NY-ESO-1- are independent prognostic factors. In conclusion, CTAs (MAGE-A4, NY-ESO-1, MAGE-A10) were more likely expressed in patients with squamous cell carcinoma and when CTAs combined with CD133, they can be better prognostic factors. Patients with CD133+NY-ESO-1+ expression may survive longer when treated with adjuvant chemotherapy, which indicates that the CD133 and CTAs might be a potential marker to guide adjuvant chemotherapy in this population.
NISHIKAWA, HIROKI; NISHIJIMA, NORIHIRO; ARIMOTO, AKIRA; INUZUKA, TADASHI; KITA, RYUICHI; KIMURA, TORU; OSAKI, YUKIO
2013-01-01
In the present era of entecavir (ETV) use for chronic hepatitis B (CHB), the prognostic factors in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) remain unclear. The aims of the present study were to investigate the prognostic factors in patients with HBV-related HCC treated with ETV who underwent curative therapy. A total of 74 HBV-related HCC patients treated with ETV who underwent curative therapy were analyzed. Predictive factors associated with overall survival (OS) and recurrence-free survival (RFS) were examined using univariate and multivariate analysis. Our study population included 49 males and 25 females with a median age of 62 years. The median observation period was 3.4 years (range, 0.2–11.5 years). The 1-, 3- and 5-year cumulative OS rates were 100, 89.8 and 89.8%, respectively. The corresponding RFS rates were 82.8, 52.1 and 25.6%, respectively. In this study, 73 patients (98.6%) achieved an HBV DNA level of <400 copies/ml during the follow-up period. No viral breakthrough hepatitis, as defined by 1 log increase from nadir, was observed during ETV therapy. According to multivariate analysis, only hepatitis B e antigen (HBeAg) positivity was significantly associated with OS [hazard ratio (HR), 0.058; 95% confidence interval (CI), 0.005–0.645; P=0.020)], whereas HCC stage (HR, 0.359; 95% CI, 0.150–0.859; P=0.021), HBeAg positivity (HR, 0.202; 95% CI, 0.088–0.463; P<0.001) and γ-glutamyl transpeptidase ≥50 IU/l (HR, 0.340; 95% CI, 0.152–0.760; P=0.009) were significant predictive factors linked to RFS. In conclusion, HBeAg positivity was significantly associated with OS and RFS in HBV-related HCC patients treated with ETV who underwent curative therapy. In such patients, close observation is required, even after curative therapy for HCC. PMID:24179497
DOE Office of Scientific and Technical Information (OSTI.GOV)
Palussiere, Jean, E-mail: J.Palussiere@bordeaux.unicancer.fr; Lagarde, Philippe, E-mail: P.Lagarde@bordeaux.unicancer.fr; Aupérin, Anne, E-mail: auperin@igr.fr
2015-02-15
PurposeTo evaluate the survival outcomes of percutaneous thermal ablation (RFA + microwaves) for patients presenting N0 non-small-cell lung cancer (NSCLC) ineligible for surgery.Materials and MethodsEighty-seven patients from two comprehensive cancer centers were included. Eighty-two patients were treated with RFA electrodes and five with microwave antenna. Overall survival (OS) and disease-free survival (DFS) were estimated and predictive factors of local tumor progression, OS and DFS identified and compared by univariate and multivariate analysesResultsMedian follow-up was 30.5 months (interquartile range 16.7–51) and tumor size was 21 mm (range 10–54 mm). Treatment was incomplete for 14 patients with a local tumor progression of 11.5, 18.3, and 21.1 % atmore » 1, 2, and 3 years, respectively. Two patients presented with neurological (grade III or IV) complications, and one died of respiratory and multivisceral failure as a result of the procedure at 29 days. In univariate analysis, increasing tumor size (P = 0.003) was the only predictive factor related to risk of local tumor progression. 5-year OS and DFS were 58.1 and 27.9 %, respectively. Sex (P = 0.044), pathology (P = 0.032), and tumor size >2 cm (P = 0.046) were prognostic factors for DFS. In multivariate analysis, pathology (P = 0.033) and tumor size >2 cm (P = 0.032) were independent prognostic factors for DFS.ConclusionsOversized and overlapping ablation of N0 NSCLC was well tolerated, effective, with few local tumor progressions, even over long-term follow-up. Increasing tumor size was the main prognostic factor linked to OS, DFS, and local tumor progression.« less
Apolinario Hidalgo, R; Suárez Cabrera, M; Geijo Martínez, M P; Bernabéu-Wittel, M; Falguera Sacrest, M; Limiñana Cañal, J M
2007-10-01
the aims of the present study were to evaluate the clinical and microbiological characteristics of patients suffering from community-acquired pneumonia attended in the Internal Medical Departments of several Spanish institutions and to analyze those prognostic factors predicting thirty-day mortality in such patients. Past medical history, symptoms and signs, radiological pattern and blood parameters including albumin and C Reactive Protein, were recorded for each patient. Time from admission to starting antibiotics (in hours) and follow-up (in days) were also recorded. Patients were stratified by the Pneumonia Severity Index in five risk classes. 389 patients were included in the study, most of them in Fine categories III to V. Mortality rate for all patients was 12.1% (48 patients), increasing up to 40% in Fine Class V. Neither age, sex nor time from admission to the start of antibiotic treatment predicted survival rates. Plasmatic levels of PCR or microbiologic diagnosis were not related to clinical outcome. In the Cox regression analysis, oriented patients (OR 0.138, IC95% 0.055-0.324), and those with normal albuminemia (OR 0.207, IC95% 0.103-0.417) showed better survival rates. On the contrary, those with active carcinoma (OR 3.2, IC95% 1.181-8.947) significantly showed a reduced life expectancy. Besides the fully accepted Fine scale criteria, albumin measurements should be included in routine evaluation in order to improve patient s prognostic classification.
Zang, R Y; Harter, P; Chi, D S; Sehouli, J; Jiang, R; Tropé, C G; Ayhan, A; Cormio, G; Xing, Y; Wollschlaeger, K M; Braicu, E I; Rabbitt, C A; Oksefjell, H; Tian, W J; Fotopoulou, C; Pfisterer, J; du Bois, A; Berek, J S
2011-01-01
Background: This study aims to identify prognostic factors and to develop a risk model predicting survival in patients undergoing secondary cytoreductive surgery (SCR) for recurrent epithelial ovarian cancer. Methods: Individual data of 1100 patients with recurrent ovarian cancer of a progression-free interval at least 6 months who underwent SCR were pooled analysed. A simplified scoring system for each independent prognostic factor was developed according to its coefficient. Internal validation was performed to assess the discrimination of the model. Results: Complete SCR was strongly associated with the improvement of survival, with a median survival of 57.7 months, when compared with 27.0 months in those with residual disease of 0.1–1 cm and 15.6 months in those with residual disease of >1 cm, respectively (P<0.0001). Progression-free interval (⩽23.1 months vs >23.1 months, hazard ratio (HR): 1.72; score: 2), ascites at recurrence (present vs absent, HR: 1.27; score: 1), extent of recurrence (multiple vs localised disease, HR: 1.38; score: 1) as well as residual disease after SCR (R1 vs R0, HR: 1.90, score: 2; R2 vs R0, HR: 3.0, score: 4) entered into the risk model. Conclusion: This prognostic model may provide evidence to predict survival benefit from secondary cytoreduction in patients with recurrent ovarian cancer. PMID:21878937
Dai, Danian; Chen, Bo; Wang, Bin; Tang, Hailin; Li, Xing; Zhao, Zhiping; Li, Xuan; Xie, Xiaoming; Wei, Weidong
2016-01-01
Previous studies have reported that the triacylglycerol (TG) level and high-density lipoprotein cholesterol (HDL-C) are connected with breast cancer. However, the prognostic utility of the TG level and the TG/HDL-C ratio (THR) as conventional biomarkers in patients with triple negative breast cancer (TNBC) has not been elucidated. In this research, we investigate and compare the predictive value of the pretreatment serum TG level and THR in TNBC patients. We evaluated 221 patients with TNBC who had pretreatment conventional blood biochemical examinations and calculated the THR. Univariate and multivariate logistic regression analyses were used to assess the effect of the TG level and the THR on overall survival (OS) and disease-free survival (DFS). The optimal cutoff values of the TG level and the THR were determined to be 0.935 mmol/L and 0.600, respectively. As shown in a Kaplan-Meier analysis, TNBC patients with a high TG level and THR had shorter OS and DFS than patients in the low-level groups ( p < 0.05). The multivariate analysis suggested that the pretreatment THR level is an independent prognostic factor of OS (HR: 1.935; 95%CI: 1.032-3.629; p = 0.040) in TNBC patients. In conclusion, our data indicate that a high THR is an independent predictor and is superior to the TG level for predicting poor clinical outcomes in TNBC patients.
Amin, Amit P; Nathan, Sandeep; Vassallo, Patricia; Calvin, James E
2009-05-20
To emphasize the importance of troponin in the context of a new score for risk stratifying acute coronary syndromes (ACS) patients. Although troponins have powerful prognostic value, current ACS scores do not fully capitalize this prognostic ability. Here, we weigh troponin status in a multiplicative manner to develop the TRACS score from previously published Rush score risk factors (RRF). 2,866 ACS patients (46.7% troponin positive) from 9 centers comprising the TRACS registry, were randomly split into derivation (n=1,422) and validation (n=1,444) cohorts. In the derivation sample, RRF sum was multiplied by 3 if troponins were positive to yield the TRACS score, which was grouped into five categories of 0-2, 3-5, 6-8, 9-11, 12-15 (multiples of 3). Predictive performance of this score to predict hospital death was ascertained in the validation sample. The TRACS score had ROC AUC of 0.71 in the validation cohort. Logistic regression, Kaplan-Meier analysis, likelihood-ratio and Bayesian Information Criterion (BIC) test indicated that weighing troponin status with 3 in the TRACS score improved the prediction of mortality. Hosmer-Lemeshow test indicated sound model fit. We demonstrate that weighing troponin as a multiple of 3 yields robust prognostication of hospital mortality in ACS patients, when used in the context of the TRACS score.
Amin, Amit P; Nathan, Sandeep; Vassallo, Patricia; Calvin, James E
2009-01-01
Structured Abstract Objective: To emphasize the importance of troponin in the context of a new score for risk stratifying acute coronary syndromes (ACS) patients. Although troponins have powerful prognostic value, current ACS scores do not fully capitalize this prognostic ability. Here, we weigh troponin status in a multiplicative manner to develop the TRACS score from previously published Rush score risk factors (RRF). Methods: 2,866 ACS patients (46.7% troponin positive) from 9 centers comprising the TRACS registry, were randomly split into derivation (n=1,422) and validation (n=1,444) cohorts. In the derivation sample, RRF sum was multiplied by 3 if troponins were positive to yield the TRACS score, which was grouped into five categories of 0-2, 3-5, 6-8, 9-11, 12-15 (multiples of 3). Predictive performance of this score to predict hospital death was ascertained in the validation sample. Results: The TRACS score had ROC AUC of 0.71 in the validation cohort. Logistic regression, Kaplan-Meier analysis, likelihood-ratio and Bayesian Information Criterion (BIC) test indicated that weighing troponin status with 3 in the TRACS score improved the prediction of mortality. Hosmer-Lemeshow test indicated sound model fit. Conclusions: We demonstrate that weighing troponin as a multiple of 3 yields robust prognostication of hospital mortality in ACS patients, when used in the context of the TRACS score. PMID:19557150
Oncologic outcome after local recurrence of chondrosarcoma: Analysis of prognostic factors.
Kim, Han-Soo; Bindiganavile, Srimanth S; Han, Ilkyu
2015-06-01
Literature on outcome after local recurrence (LR) in chondrosarcoma is scarce and better appreciation of prognostic factors is needed. (1) To evaluate post-LR oncologic outcomes of disease-specific survival and subsequent LR and (2) to identify prognostic factors for post-LR oncologic outcomes. Review of 28 patients with locally recurrent chondrosarcoma from the original cohort of 150 patients, who were treated surgically with or without adjuvants between 1982 and 2011, was performed. Mean age was 46 years (range, 21-73) which included 20 males and 8 females with mean follow up of 8.4 ± 7.5 years (range, 1.2-31.0). Post-LR survival at 5 years was 58.6 ± 10.3%. Age greater than 50 years (P = 0.011) and LR occurring within 1 year of primary surgery (P = 0.011) independently predicted poor survival. Seven patients suffered subsequent LR, which was significantly affected by surgical margin for LR (P = 0.038). Long-term survival of locally recurrent chondrosarcoma is achievable in a substantial number of patients. Older age at onset of LR and shorter interval from primary surgery to LR identifies high risk patients for poor post-LR survival while, wide surgical margins at LR surgery reduces the risk of subsequent LR. © 2015 Wiley Periodicals, Inc.
Kim, Dong Suk; Cho, Kang Su; Lee, Young Hoon; Cho, Nam Hoon; Oh, Young Taek
2010-01-01
We examined whether the presence and severity of preoperative hydronephrosis have prognostic significance in patients who underwent radical cystectomy for transitional cell carcinoma of the bladder. The medical records of 457 patients who underwent radical cystectomy for bladder cancer between 1986 and 2005 were retrospectively reviewed. Following the Society for Fetal Urology grading system, patients were divided into low-, and high-grade hydronephrosis groups. Clinicopathologic factors associated with preoperative hydronephrosis and survival were evaluated. Of a total of 406 patients, unilateral hydronephrosis was found in 74 (18.2%), bilateral hydronephrosis in 11 (2.7%), and no hydronephoris in 321 (79.1%). Low-grade hydronephrosis was found in 57 (12.2%) patients and high-grade hydronephrosis in 28 (6%). Preoperative hydronephrosis was related to higher pT stage and lymph node invasion. In univariate analysis, the presence of hydronephrosis, hydronephrosis grade, age, pT and pN stage, tumor grade, surgical margin, number of retrieved nodes, carcinoma in situ, and lymphovascular invasion were significant prognostic factors for cancer-specific survival. In multivariate analysis, bilateral hydronephrosis and high-grade hydronephrosis remained significant predictors for decreased survival. The presence of preoperative hydronephrosis, and high-grade hydronephrosis are significant prognostic factors in patients with bladder cancer after radical cystectomy. PMID:20191034
EMMPRIN/CD147 is an independent prognostic biomarker in cutaneous melanoma.
Caudron, Anne; Battistella, Maxime; Feugeas, Jean-Paul; Pages, Cécile; Basset-Seguin, Nicole; Mazouz Dorval, Sarra; Funck Brentano, Elisa; Sadoux, Aurélie; Podgorniak, Marie-Pierre; Menashi, Suzanne; Janin, Anne; Lebbé, Céleste; Mourah, Samia
2016-08-01
CD147 has been implicated in melanoma invasion and metastasis mainly through increasing metalloproteinase synthesis and regulating VEGF/VEGFR signalling. In this study, the prognostic value of CD147 expression was investigated in a cohort of 196 cutaneous melanomas including 136 consecutive primary malignant melanomas, 30 lymph nodes, 16 in-transit and 14 visceral metastases. A series of 10 normal skin, 10 blue nevi and 10 dermal nevi was used as control. CD147 expression was assessed by immunohistochemistry, and the association of its expression with the clinicopathological characteristics of patients and survival was evaluated using univariate and multivariate statistical analyses. Univariate analysis showed that high CD147 expression was significantly associated with metastatic potential and with a reduced overall survival (P < 0.05 for both) in primary melanoma patients. CD147 expression level was correlated with histological factors which were associated with prognosis: Clark level, ulceration status and more particularly with Breslow index (r = 0.7, P < 10(-8) ). Multivariate analysis retained CD147 expression level and ulceration status as predicting factors for metastasis and overall survival (P < 0.05 for both). CD147 emerges as an important factor in the aggressive behaviour of melanoma and deserves further evaluation as an independent prognostic biomarker. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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.
Prognostic Factors in Cholinesterase Inhibitor Poisoning.
Sun, In O; Yoon, Hyun Ju; Lee, Kwang Young
2015-09-28
Organophosphates and carbamates are insecticides that are associated with high human mortality. The purpose of this study is to investigate the prognostic factors affecting survival in patients with cholinesterase inhibitor (CI) poisoning. This study included 92 patients with CI poisoning in the period from January 2005 to August 2013. We divided these patients into 2 groups (survivors vs. non-survivors), compared their clinical characteristics, and analyzed the predictors of survival. The mean age of the included patients was 56 years (range, 16-88). The patients included 57 (62%) men and 35 (38%) women. When we compared clinical characteristics between the survivor group (n=81, 88%) and non-survivor group (n=11, 12%), there were no differences in renal function, pancreatic enzymes, or serum cholinesterase level, except for serum bicarbonate level and APACHE II score. The serum bicarbonate level was lower in non-survivors than in survivors (12.45±2.84 vs. 18.36±4.73, P<0.01). The serum APACHE II score was higher in non-survivors than in survivors (24.36±5.22 vs. 12.07±6.67, P<0.01). The development of pneumonia during hospitalization was higher in non-survivors than in survivors (n=9, 82% vs. n=31, 38%, P<0.01). In multiple logistic regression analysis, serum bicarbonate concentration, APACHE II score, and pneumonia during hospitalization were the important prognostic factors in patients with CI poisoning. Serum bicarbonate and APACHE II score are useful prognostic factors in patients with CI poisoning. Furthermore, pneumonia during hospitalization was also important in predicting prognosis in patients with CI poisoning. Therefore, prevention and active treatment of pneumonia is important in the management of patients with CI poisoning.
Franceschi, Enrico; Tosoni, Alicia; Minichillo, Santino; Depenni, Roberta; Paccapelo, Alexandro; Bartolini, Stefania; Michiara, Maria; Pavesi, Giacomo; Urbini, Benedetta; Crisi, Girolamo; Cavallo, Michele A; Tosatto, Luigino; Dazzi, Claudio; Biasini, Claudia; Pasini, Giuseppe; Balestrini, Damiano; Zanelli, Francesca; Ramponi, Vania; Fioravanti, Antonio; Giombelli, Ermanno; De Biase, Dario; Baruzzi, Agostino; Brandes, Alba A
2018-04-01
Clinical and molecular factors are essential to define the prognosis in patients with glioblastoma (GBM). O6-methylguanine-DNA methyltransferase (MGMT) methylation status, age, Karnofsky Performance Status (KPS), and extent of surgical resection are the most relevant prognostic factors. Our investigation of the role of gender in predicting prognosis shows a slight survival advantage for female patients. We performed a prospective evaluation of the Project of Emilia Romagna on Neuro-Oncology (PERNO) registry to identify prognostic factors in patients with GBM who received standard treatment. A total of 169 patients (99 males [58.6%] and 70 females [41.4%]) were evaluated prospectively. MGMT methylation was evaluable in 140 patients. Among the male patients, 36 were MGMT methylated (25.7%) and 47 were unmethylated (33.6%); among the female patients, 32 were methylated (22.9%) and 25 were unmethylated (17.9%). Survival was longer in the methylated females compared with the methylated males (P = 0.028) but was not significantly different between the unmethylated females and the unmethylated males (P = 0.395). In multivariate analysis, gender and MGMT methylation status considered together (methylated females vs. methylated males; hazard ratio [HR], 0.459; 95% confidence interval [CI], 0.242-0.827; P = 0.017), age (HR, 1.025; 95% CI, 1.002-1.049; P = 0.032), and KPS (HR, 0.965; 95% CI, 0.948-0.982; P < 0.001) were significantly correlated with survival. Survival was consistently longer among MGMT methylated females compared with males. Gender can be considered as a further prognostic factor. Copyright © 2018 Elsevier Inc. All rights reserved.
Loupakis, Fotios; Adams, Richard A.; Seymour, Matthew T.; Heinemann, Volker; Schmoll, Hans-Joachim; Douillard, Jean-Yves; Hurwitz, Herbert; Fuchs, Charles S.; Diaz-Rubio, Eduardo; Porschen, Rainer; Tournigand, Christophe; Chibaudel, Benoist; Falcone, Alfredo; Tebbutt, Niall C.; Punt, Cornelis J.A.; Hecht, J. Randolph; Bokemeyer, Carsten; Van Cutsem, Eric; Goldberg, Richard M.; Saltz, Leonard B.; de Gramont, Aimery; Sargent, Daniel J.; Lenz, Heinz-Josef
2016-01-01
Purpose In recent retrospective analyses of early-stage colorectal cancer (CRC), low and high body mass index (BMI) scores were associated with worsened outcomes. Whether BMI is a prognostic or predictive factor in metastatic CRC (mCRC) is unclear. Patients and Methods Individual data from 21,149 patients enrolled onto 25 first-line mCRC trials during 1997 to 2012 were pooled. We assessed both prognostic and predictive effects of BMI on overall survival and progression-free survival, and we accounted for patient and tumor characteristics and therapy type (targeted v nontargeted). Results BMI was prognostic for overall survival (P < .001) and progression-free survival (P < .001), with an L-shaped pattern. That is, risk of progression and/or death was greatest for low BMI; risk decreased as BMI increased to approximately 28 kg/m2, and then it plateaued. Relative to obese patients, patients with a BMI of 18.5 kg/m2 had a 27% increased risk of having a PFS event (95% CI, 20% to 34%) and a 50% increased risk of death (95% CI, 43% to 56%). Low BMI was associated with poorer survival for men than women (interaction P < .001). BMI was not predictive of treatment effect. Conclusion Low BMI is associated with an increased risk of progression and death among the patients enrolled on the mCRC trials, with no increased risk for elevated BMI, in contrast to the adjuvant setting. Possible explanations include negative effects related to cancer cachexia in patients with low BMI, increased drug delivery or selection bias in patients with high BMI, and potential for an interaction between BMI and molecular signaling pathways. PMID:26503203
Jian-Hui, Chen; Iskandar, Edward Arthur; Cai, Sh-Irong; Chen, Chuang-Qi; Wu, Hui; Xu, Jian-Bo; He, Yu-Long
2016-03-01
The preoperative nutritional and immunological statuses have an important impact in predicting the survival outcome of patients with various types of malignant tumors. Our study aimed to explore the clinical significance and predictive prognostic potential of Onodera's prognostic nutritional index (PNI) in patients with colorectal carcinoma. This retrospective study included a total of 1321 patients who were diagnosed with colorectal cancer and who had been surgically treated between January 1994 and December 2007. The PNI level was determined according the following formula: 10 × serum albumin (g/dL) + 0.005 × total lymphocyte count (per mm(3)). The impact of PNI on clinicopathological features and overall survival (OS) was determined. The optimal cutoff value of PNI was set at 45. Patients in the low-PNI group had a greater potential to have aggressive histological features, advanced tumors (T), nodal involvement (N), metastasis (M), and TNM stage than those in the high-PNI group. The low-PNI group had a worse OS than the high-PNI group (5-year survival rate 56.1 vs 64.8 %, respectively; P < 0.05). Furthermore, the PNI value was an independent prognostic factor for colorectal cancer in this study. The OS was significantly lower in the low-PNI group than in the high-PNI group in patients with TNM stage II and III diseases. Preoperative PNI is a simple and useful marker to predict clinicopathological features and long-term survival outcome in patients with colorectal carcinoma. PNI analysis should be included in the routine assessment of patients with locally advanced colorectal cancer.
Koenecke, Christian; Göhring, Gudrun; de Wreede, Liesbeth C.; van Biezen, Anja; Scheid, Christof; Volin, Liisa; Maertens, Johan; Finke, Jürgen; Schaap, Nicolaas; Robin, Marie; Passweg, Jakob; Cornelissen, Jan; Beelen, Dietrich; Heuser, Michael; de Witte, Theo; Kröger, Nicolaus
2015-01-01
The aim of this study was to determine the impact of the revised 5-group International Prognostic Scoring System cytogenetic classification on outcome after allogeneic stem cell transplantation in patients with myelodysplastic syndromes or secondary acute myeloid leukemia who were reported to the European Society for Blood and Marrow Transplantation database. A total of 903 patients had sufficient cytogenetic information available at stem cell transplantation to be classified according to the 5-group classification. Poor and very poor risk according to this classification was an independent predictor of shorter relapse-free survival (hazard ratio 1.40 and 2.14), overall survival (hazard ratio 1.38 and 2.14), and significantly higher cumulative incidence of relapse (hazard ratio 1.64 and 2.76), compared to patients with very good, good or intermediate risk. When comparing the predictive performance of a series of Cox models both for relapse-free survival and for overall survival, a model with simplified 5-group cytogenetics (merging very good, good and intermediate cytogenetics) performed best. Furthermore, monosomal karyotype is an additional negative predictor for outcome within patients of the poor, but not the very poor risk group of the 5-group classification. The revised International Prognostic Scoring System cytogenetic classification allows patients with myelodysplastic syndromes to be separated into three groups with clearly different outcomes after stem cell transplantation. Poor and very poor risk cytogenetics were strong predictors of poor patient outcome. The new cytogenetic classification added value to prediction of patient outcome compared to prediction models using only traditional risk factors or the 3-group International Prognostic Scoring System cytogenetic classification. PMID:25552702
Low T3 syndrome as a predictor of poor prognosis in chronic lymphocytic leukemia.
Gao, Rui; Chen, Rui-Ze; Xia, Yi; Liang, Jin-Hua; Wang, Li; Zhu, Hua-Yuan; Zhu Wu, Jia-; Fan, Lei; Li, Jian-Yong; Yang, Tao; Xu, Wei
2018-02-19
Low triiodothyronine (T3) state is associated with poor prognosis in critical acute and prolonged illness. However, the information on thyroid dysfunction and cancer is limited. The aim of our study was to evaluate the prognostic value of low T3 syndrome in chronic lymphocytic leukemia (CLL). Two hundred and fifty-eight patients with detailed thyroid hormone profile at CLL diagnosis were enrolled. Low T3 syndrome was defined by low free T3 (FT3) level accompanied by normal-to-low free tetraiodothyronine (FT4) and thyroid-stimulating hormone (TSH) levels. A propensity score-matched method was performed to balance the baseline characteristics. Multivariate Cox regression analyses screened the independent prognostic factors related to time-to-first-treatment (TTFT) and cancer-specific survival (CSS). Area under the curve (AUC) assessed the predictive accuracy of CLL-International Prognostic Index (IPI) together with low T3 syndrome. The results showed that 37 (14.34%) patients had low T3 syndrome, which was significantly associated with unfavorable TTFT and CSS in the propensity-matched cohort, and it was an independent prognostic indicator for both TTFT and CSS. Serum FT3 level was positively related to protein metabolism and anemia, and inversely related to inflammatory state. Patients with only low FT3 demonstrated better survival than those with synchronously low FT3 and FT4, while those with synchronously low FT3, FT4 and TSH had the worst clinical outcome. Low T3 syndrome together with CLL-IPI had larger AUCs compared with CLL-IPI alone in TTFT and CSS prediction. In conclusion, low T3 syndrome may be a good candidate for predicting prognosis in future clinical practice of CLL. © 2018 UICC.
Kimbung, Siker; Kovács, Anikó; Bendahl, Pär-Ola; Malmström, Per; Fernö, Mårten; Hatschek, Thomas; Hedenfalk, Ingrid
2014-02-01
Predicting any future metastatic site of early-stage breast cancer is important as it significantly influences the prognosis of advanced disease. This study aimed at investigating the potential of claudin-2, over-expressed in breast cancer liver metastases, as a biomarker for predicting liver metastatic propensity in primary breast cancer. Claudin-2 expression was analyzed in two independent cohorts. Cohort 1 included 304 women with metastatic breast cancer diagnosed between 2002 and 2007, while cohort 2 included 237 premenopausal women with early-stage node-negative breast cancer diagnosed between 1991 and 1994. Global transcriptional profiling of fine-needle aspirates from metastases was performed, followed by immunohistochemical analyses in archival primary tumor tissue. Associations between claudin-2 expression and relapse site were assessed by univariable and multivariable Cox regression models including conventional prognostic factors. Two-sided statistical tests were used. CLDN2 was significantly up-regulated (P < 0.001) in liver metastases compared to other metastatic sites. Claudin-2 protein was more frequently expressed in primary tumors from patients who subsequently developed liver metastases (P = 0.02) and high expression was associated with a shorter metastasis-free interval (cohort 1, HR = 1.4, 95% CI = 1.0-1.9; cohort 2, HR = 2.2, 95% CI = 1.3-3.5). Specifically, a significantly shorter interval between primary tumor diagnosis and liver-specific recurrence was observed among patients with high levels of claudin-2 expression in the primary tumor (cohort 1, HR = 2.3, 95% CI = 1.3-3.9). These results suggest a novel role for claudin-2 as a prognostic biomarker with the ability to predict not only the likelihood of a breast cancer recurrence, but more interestingly, the liver metastatic potential of the primary tumor. Copyright © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
Collins, Vincent Peter; Ichimura, Koichi; Di, Ying; Pearson, Danita; Chan, Ray; Thompson, Lindsay C; Gabe, Rhian; Brada, Michael; Stenning, Sally P
2014-06-20
We evaluated the prognostic and predictive value of a range of molecular changes in the setting of a randomised trial comparing standard PCV (procarbazine, CCNU (1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea) and vincristine) chemotherapy with the standard temozolomide (TMZ) 5-day (200 mg/m2/day) schedule and a 21-day (100 mg/m2/day) schedule in chemo-naïve, high-grade glioma (non-oligodendroglial tumours; WHO (World Health Organisation) grades III and IV) patients at first progression following radiotherapy.354 samples (79.2%) from the first operation of the 447 randomised patients provided enough tumour DNA for some or all parts of the study. Genome-wide array comparative genomic hybridisation (aCGH), mutation analysis of IDH1/2 and TP53 and methylation analyses of the MGMT CpG-island was done.84% of grade III tumours and 17% of grade IV had IDH1 or IDH2 mutations that conferred a better prognosis in both; MGMT methylation (defined as average value across 16 CpGs ≥ 10%) occurred in 75% of tumours and was also associated with improved survival. Both were of independent prognostic value after accounting for clinical factors and tumour grade. None of the molecular changes investigated gave clear evidence of a predictive benefit of TMZ over PCV or 21-day TMZ over 5-day TMZ although power was limited and a role for MGMT methylation could not be ruled out. Loss of 1p and 19q was seen in only 4 patients although hemizygous loss of 1p36 occurred in 20%.The findings support reports that IDH1/2 mutations and MGMT methylation can be used in addition to tumour grade and clinical factors to predict survival in patients with recurrent high grade gliomas when treated with any of the therapy regimes used.
Yun, Sumi; Kwak, Yoonjin; Nam, Soo Kyung; Seo, An Na; Oh, Heung-Kwon; Kim, Duck-Woo; Kang, Sung-Bum; Lee, Hye Seung
2018-01-17
Molecular treatments targeting epidermal growth factor receptors (EGFRs) are important strategies for advanced colorectal cancer (CRC). However, clinicopathologic implications of EGFRs and EGFR ligand signaling have not been fully evaluated. We evaluated the expression of EGFR ligands and correlation with their receptors, clinicopathologic factors, and patients' survival with CRC. The expression of EGFR ligands, including heparin binding epidermal growth factor like growth factor (HBEGF), transforming growth factor (TGF), betacellulin, and epidermal growth factor (EGF), were evaluated in 331 consecutive CRC samples using mRNA in situ hybridization (ISH). We also evaluated the expression status of EGFR, human epidermal growth factor receptor 2 (HER2), HER3, and HER4 using immunohistochemistry and/or silver ISH. Unlike low incidences of TGF (38.1%), betacellulin (7.9%), and EGF (2.1%), HBEGF expression was noted in 62.2% of CRC samples. However, the expression of each EGFR ligand did not reveal significant correlations with survival. The combined analyses of EGFR ligands and EGFR expression indicated that the ligands‒/EGFR+ group showed a significant association with the worst disease-free survival (DFS, p=0.018) and overall survival (OS, p=0.005). It was also an independent, unfavorable prognostic factor for DFS (p=0.026) and OS (p=0.007). Additionally, HER4 nuclear expression, regardless of ligand expression, was an independent, favorable prognostic factor for DFS (p=0.034) and OS (p=0.049), by multivariate analysis. Ligand-independent EGFR overexpression was suggested to have a significant prognostic impact; thus, the expression status of EGFR ligands, in addition to EGFR, might be necessary for predicting patients' outcome in CRC.
Preoperative prognostic factors for mortality in peptic ulcer perforation: a systematic review.
Møller, Morten Hylander; Adamsen, Sven; Thomsen, Reimar Wernich; Møller, Ann Merete
2010-08-01
Mortality and morbidity following perforated peptic ulcer (PPU) is substantial and probably related to the development of sepsis. During the last three decades a large number of preoperative prognostic factors in patients with PPU have been examined. The aim of this systematic review was to summarize available evidence on these prognostic factors. MEDLINE (January 1966 to June 2009), EMBASE (January 1980 to June 2009), and the Cochrane Library (Issue 3, 2009) were screened for studies reporting preoperative prognostic factors for mortality in patients with PPU. The methodological quality of the included studies was assessed. Summary relative risks with 95% confidence intervals for the identified prognostic factors were calculated and presented as Forest plots. Fifty prognostic studies with 37 prognostic factors comprising a total of 29,782 patients were included in the review. The overall methodological quality was acceptable, yet only two-thirds of the studies provided confounder adjusted estimates. The studies provided strong evidence for an association of older age, comorbidity, and use of NSAIDs or steroids with mortality. Shock upon admission, preoperative metabolic acidosis, tachycardia, acute renal failure, low serum albumin level, high American Society of Anaesthesiologists score, and preoperative delay >24 h were associated with poor prognosis. In patients with PPU, a number of negative prognostic factors can be identified prior to surgery, and many of these seem to be related to presence of the sepsis syndrome.
Wang, Liang; Xia, Zhong-jun; Huang, Hui-qiang; Lu, Yue; Zhang, Yu-jing
2012-11-01
We conducted a retrospective study of 135 patients of stage IE/IIE extranodal natural killer/T cell lymphoma, nasal type (ENKTL) treated with CHOP as induction chemotherapy to find some valuable prognostic factors and analyze the usefulness of International Prognostic Index (IPI) and Korean Prognostic Index (KPI) in predicting prognosis. Most of the patients were in the low-risk group (IPI score 0-1). Complete remission (CR) after induction chemotherapy was achieved in 31.8 % of the patients, which increased to 69.6 % after radiotherapy. The 2-, 5-, and 10-year overall survival (OS) rates were 60, 48, and 43 %, respectively. Patients with better performance status (ECOG 0-1), normal serum LDH level, without local invasiveness, low KPI scores, and IPI score of 0 had significantly better overall survival (P < 0.05) in univariate analysis. Using multivariate analysis, we identified serum LDH level, ECOG PS score and local invasiveness to be independent prognostic factors. In conclusion, ENKTL is an aggressive lymphoma that shows heterogeneity. The IPI and KPI score systems should be improved further to classify patients into different groups, and should be validated in larger prospective trials. Due to the multi-drug resistance mechanism of ENKTL, CHOP is no longer the state of art and novel drugs should be incorporated into future treatments.
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.
de la Motte Rouge, Thibault; Pautier, Patricia; Genestie, Catherine; Rey, Annie; Gouy, Sébastien; Leary, Alexandra; Haie-Meder, Christine; Kerbrat, Pierre; Culine, Stéphane; Fizazi, Karim; Lhommé, Catherine
2016-09-01
The ovarian yolk sac tumor (OYST) is a very rare malignancy arising in young women. Our objective was to determine whether an early decline in serum alpha-fetoprotein (AFP) during chemotherapy has a prognostic impact. This retrospective study is based on prospectively recorded OYST cases at Gustave Roussy (Cancer Treatment Center). Survival curves were estimated using the Kaplan-Meier method. The serum AFP decline was calculated with the formula previously developed and validated in male patients with poor prognosis non-seminomatous germ cell tumors. Univariate and multivariate analyses were performed using the log-rank test and logistic regression, respectively. Data on AFP were available to calculate an early AFP decline in 57 patients. All patients had undergone surgery followed by chemotherapy. The 5-year overall survival (OS) and event-free survival (EFS) rates were 86% (95% CI: 74%-93%) and 84% (95% CI: 73%-91%), respectively. The disease stage, presence of ascites at presentation, use of the BEP regimen, serum AFP half-life and an early AFP decline were significantly predictive factors for OS and EFS in the univariate analysis. The OS rate was 100% and 49% (95% CI: 26%-72%) in patients with a favorable AFP decline and in those with an unfavorable decline, respectively (p<0.001). In the multivariate analysis, only the presence of ascites at diagnosis (RR=7.3, p=0.03) and an unfavorable early AFP decline (RR=16.9, p<0.01) were significant negative predictive factors for OS. An early AFP decline during chemotherapy is an independent prognostic factor in patients with OYSTs. No conflict of interest. Copyright © 2016. Published by Elsevier Inc.
Lee, Geewon; Kim, Ki Uk; Lee, Ji Won; Suh, Young Ju; Jeong, Yeon Joo
2017-05-01
Background Although fibrotic idiopathic interstitial pneumonias (IIPs) alone and those combined with pulmonary emphysema are naturally progressive diseases, the process of deterioration and outcomes are variable. Purpose To evaluate and compare serial changes of computed tomography (CT) abnormalities and prognostic predictive factors in fibrotic IIPs alone and those combined with pulmonary emphysema. Material and Methods A total of 148 patients with fibrotic IIPs alone (82 patients) and those combined with pulmonary emphysema (66 patients) were enrolled. Semi-quantitative CT analysis was used to assess the extents of CT characteristics which were evaluated on initial and follow-up CT images. Univariate and multivariate analyses were performed to assess the effects of clinical and CT variables on survival. Results Significant differences were noted between fibrotic scores, as determined using initial CT scans, in the fibrotic IIPs alone (21.22 ± 9.83) and those combined with pulmonary emphysema groups (14.70 ± 7.28) ( P < 0.001). At follow-up CT scans, changes in the extent of ground glass opacities (GGO) were greater ( P = 0.031) and lung cancer was more prevalent ( P = 0.001) in the fibrotic IIPs combined with pulmonary emphysema group. Multivariate Cox proportional hazards analysis showed changes in the extent of GGO (hazard ratio, 1.056) and the presence of lung cancer (hazard ratio, 4.631) were predictive factors of poor survivals. Conclusion Although patients with fibrotic IIPs alone and those combined with pulmonary emphysema have similar mortalities, lung cancer was more prevalent in patients with fibrotic IIPs combined with pulmonary emphysema. Furthermore, changes in the extent of GGO and the presence of lung cancer were independent prognostic factors of poor survivals.
Cohen, Jean-David; Dougados, Maxime; Goupille, Philippe; Cantagrel, Alain; Meyer, Olivier; Sibilia, Jean; Daurès, Jean-Pierre; Combe, Bernard
2006-10-01
To evaluate and determine prognostic factors of 5-year quality of life in patients with early rheumatoid arthritis (RA). A cohort of 191 patients with RA and disease duration < 1 year was prospectively followed over 5 years. The outcome measure was quality of life as assessed by the Arthritis Impact Measurement Scales 2 (AIMS2). Univariate analysis, then stepwise multiple logistic regression, was used to find independent baseline prognostic variables. After accounting for death, loss of followup, and missing data, 158 patients (82.72%) were included in the analysis. The mean AIMS2 physical, symptom, psychological, social interaction, and work scores after 5 years were 1.6 (range 0-6.88), 4.0 (0-10), 3.48 (0-9.22), 4.06 (0-8.69), and 1.87 (0-8.13), respectively. The AIMS2 physical component was significantly correlated with Health Assessment Questionnaire (HAQ) score at 5 years. Logistic regression analysis revealed that the baseline values able to predict the 5-year physical, psychological, symptom, social interaction, and work status were, respectively: HAQ score and erythrocyte sedimentation rate (ESR), body mass index (BMI), HAQ; erosion score and sex, HAQ; ESR and anti-perinuclear antibody; matrix metalloproteinase-3 (MMP3) level, joint space narrowing, and tender joint scores; HAQ score and age. The multidimensional structure of the AIMS2 allowed us to assess the 5-year health-related quality of life in early RA. Using this instrument as an outcome variable, prognostic factors were selected and varied widely depending on the evaluated domain. The baseline HAQ score was the best predictive factor of 4 of the 5 domains of the AIMS2.
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.
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
Zabor, Emily C; Coit, Daniel; Gershenwald, Jeffrey E; McMasters, Kelly M; Michaelson, James S; Stromberg, Arnold J; Panageas, Katherine S
2018-02-22
Prognostic models are increasingly being made available online, where they can be publicly accessed by both patients and clinicians. These online tools are an important resource for patients to better understand their prognosis and for clinicians to make informed decisions about treatment and follow-up. The goal of this analysis was to highlight the possible variability in multiple online prognostic tools in a single disease. To demonstrate the variability in survival predictions across online prognostic tools, we applied a single validation dataset to three online melanoma prognostic tools. Data on melanoma patients treated at Memorial Sloan Kettering Cancer Center between 2000 and 2014 were retrospectively collected. Calibration was assessed using calibration plots and discrimination was assessed using the C-index. In this demonstration project, we found important differences across the three models that led to variability in individual patients' predicted survival across the tools, especially in the lower range of predictions. In a validation test using a single-institution data set, calibration and discrimination varied across the three models. This study underscores the potential variability both within and across online tools, and highlights the importance of using methodological rigor when developing a prognostic model that will be made publicly available online. The results also reinforce that careful development and thoughtful interpretation, including understanding a given tool's limitations, are required in order for online prognostic tools that provide survival predictions to be a useful resource for both patients and clinicians.
Number of negative lymph nodes as a prognostic factor in esophageal squamous cell carcinoma.
Ma, Mingquan; Tang, Peng; Jiang, Hongjing; Gong, Lei; Duan, Xiaofeng; Shang, Xiaobin; Yu, Zhentao
2017-10-01
The aim of this study is to investigate the number of negative lymph nodes (NLNs) as a prognostic factor for survival in patients with resected esophageal squamous cell carcinoma. A total of 381 esophageal squamous cell carcinoma patients who had underwent surgical resection as the primary treatment was enrolled into this retrospective study. The impact of number of NLNs on patient's overall survival was assessed and compared with the factors among the current tumor-nodes-metastasis (TNM) staging system. The number of NLNs was closely related to the overall survival, and the 5-year survival rate was 45.4% for number of NLNs of >20 (142 cases) and 26.4% for NLNs ≤ 20 (239 cases) (P = 0.001). In multivariate survival analysis, the number of NLNs remained an independent prognostic factor (P = 0.002) as did the other current TNM factors. For subgroup analysis, the predictive value of number of NLNs was significant in patients with T3 or T4 disease (P = 0.001) and patients with N1 and N2-3 disease (P = 0.025, 0.043), but not in patients with T1 or T2 disease or patients with N0 disease. The number of NLNs, which represents the extent of lymphadenectomy for esophageal squamous cell carcinoma, could impact the overall survival of patients with resected esophageal squamous cell carcinoma, especially among those with nodal-positive disease and advanced T-stage tumor. © 2016 John Wiley & Sons Australia, Ltd.
Guglielminotti, Jean; Dechartres, Agnès; Mentré, France; Montravers, Philippe; Longrois, Dan; Laouénan, Cedric
2015-10-01
Prognostic research studies in anesthesiology aim to identify risk factors for an outcome (explanatory studies) or calculate the risk of this outcome on the basis of patients' risk factors (predictive studies). Multivariable models express the relationship between predictors and an outcome and are used in both explanatory and predictive studies. Model development demands a strict methodology and a clear reporting to assess its reliability. In this methodological descriptive review, we critically assessed the reporting and methodology of multivariable analysis used in observational prognostic studies published in anesthesiology journals. A systematic search was conducted on Medline through Web of Knowledge, PubMed, and journal websites to identify observational prognostic studies with multivariable analysis published in Anesthesiology, Anesthesia & Analgesia, British Journal of Anaesthesia, and Anaesthesia in 2010 and 2011. Data were extracted by 2 independent readers. First, studies were analyzed with respect to reporting of outcomes, design, size, methods of analysis, model performance (discrimination and calibration), model validation, clinical usefulness, and STROBE (i.e., Strengthening the Reporting of Observational Studies in Epidemiology) checklist. A reporting rate was calculated on the basis of 21 items of the aforementioned points. Second, they were analyzed with respect to some predefined methodological points. Eighty-six studies were included: 87.2% were explanatory and 80.2% investigated a postoperative event. The reporting was fairly good, with a median reporting rate of 79% (75% in explanatory studies and 100% in predictive studies). Six items had a reporting rate <36% (i.e., the 25th percentile), with some of them not identified in the STROBE checklist: blinded evaluation of the outcome (11.9%), reason for sample size (15.1%), handling of missing data (36.0%), assessment of colinearity (17.4%), assessment of interactions (13.9%), and calibration (34.9%). When reported, a few methodological shortcomings were observed, both in explanatory and predictive studies, such as an insufficient number of events of the outcome (44.6%), exclusion of cases with missing data (93.6%), or categorization of continuous variables (65.1%.). The reporting of multivariable analysis was fairly good and could be further improved by checking reporting guidelines and EQUATOR Network website. Limiting the number of candidate variables, including cases with missing data, and not arbitrarily categorizing continuous variables should be encouraged.
Scholten-Peeters, Gwendolijne G M; Verhagen, Arianne P; Bekkering, Geertruida E; van der Windt, Daniëlle A W M; Barnsley, Les; Oostendorp, Rob A B; Hendriks, Erik J M
2003-07-01
We present a systematic review of prospective cohort studies. Our aim was to assess prognostic factors associated with functional recovery of patients with whiplash injuries. The failure of some patients to recover following whiplash injury has been linked to a number of prognostic factors. However, there is some inconsistency in the literature and there have been no systematic attempts to analyze the level of evidence for prognostic factors in whiplash recovery. Studies were selected for inclusion following a comprehensive search of MEDLINE, EMBASE, CINAHL, the database of the Dutch Institute of Allied Health Professions up until April 2002 and hand searches of the reference lists of retrieved articles. Studies were selected if the objective was to assess prognostic factors associated with recovery; the design was a prospective cohort study; the study population included at least an identifiable subgroup of patients suffering from a whiplash injury; and the paper was a full report published in English, German, French or Dutch. The methodological quality was independently assessed by two reviewers. A study was considered to be of 'high quality' if it satisfied at least 50% of the maximum available quality score. Two independent reviewers extracted data and the association between prognostic factors and functional recovery was calculated in terms of risk estimates. Fifty papers reporting on twenty-nine cohorts were included in the review. Twelve cohorts were considered to be of 'high quality'. Because of the heterogeneity of patient selection, type of prognostic factors and outcome measures, no statistical pooling was able to be performed. Strong evidence was found for high initial pain intensity being an adverse prognostic factor. There was strong evidence that for older age, female gender, high acute psychological response, angular deformity of the neck, rear-end collision, and compensation not being associated with an adverse prognosis. Several physical (e.g. restricted range of motion, high number of complaints), psychosocial (previous psychological problems), neuropsychosocial factors (nervousness), crash related (e.g. accident on highway) and treatment related factors (need to resume physiotherapy) showed limited prognostic value for functional recovery. High initial pain intensity is an important predictor for delayed functional recovery for patients with whiplash injury. Often mentioned factors like age, gender and compensation do not seem to be of prognostic value. Scientific information about prognostic factors can guide physicians or other care providers to direct treatment and to probably prevent chronicity.
Evaluating surrogate endpoints, prognostic markers, and predictive markers: Some simple themes.
Baker, Stuart G; Kramer, Barnett S
2015-08-01
A surrogate endpoint is an endpoint observed earlier than the true endpoint (a health outcome) that is used to draw conclusions about the effect of treatment on the unobserved true endpoint. A prognostic marker is a marker for predicting the risk of an event given a control treatment; it informs treatment decisions when there is information on anticipated benefits and harms of a new treatment applied to persons at high risk. A predictive marker is a marker for predicting the effect of treatment on outcome in a subgroup of patients or study participants; it provides more rigorous information for treatment selection than a prognostic marker when it is based on estimated treatment effects in a randomized trial. We organized our discussion around a different theme for each topic. "Fundamentally an extrapolation" refers to the non-statistical considerations and assumptions needed when using surrogate endpoints to evaluate a new treatment. "Decision analysis to the rescue" refers to use the use of decision analysis to evaluate an additional prognostic marker because it is not possible to choose between purely statistical measures of marker performance. "The appeal of simplicity" refers to a straightforward and efficient use of a single randomized trial to evaluate overall treatment effect and treatment effect within subgroups using predictive markers. The simple themes provide a general guideline for evaluation of surrogate endpoints, prognostic markers, and predictive markers. © The Author(s) 2014.
Prognostic value of sex-hormone receptor expression in non-muscle-invasive bladder cancer.
Nam, Jong Kil; Park, Sung Woo; Lee, Sang Don; Chung, Moon Kee
2014-09-01
We investigated sex-hormone receptor expression as predicting factor of recurrence and progression in patients with non-muscle invasive bladder cancer. We retrospectively evaluated tumor specimens from patients treated for transitional cell carcinoma of the bladder at our institution between January 2006 and January 2011. Performing immunohistochemistry using a monoclonal androgen receptor antibody and monoclonal estrogen receptor-beta antibody on paraffin-embedded tissue sections, we assessed the relationship of immunohistochemistry results and prognostic factors such as recurrence and progression. A total of 169 patients with bladder cancer were evaluated in this study. Sixty-threepatients had expressed androgen receptors and 52 patients had estrogen receptor beta. On univariable analysis, androgen receptor expression was significant lower in recurrence rates (p=0.001), and estrogen receptor beta expression was significant higher in progression rates (p=0.004). On multivariable analysis, significant association was found between androgen receptor expression and lower recurrence rates (hazard ratio=0.500; 95% confidence interval, 0.294 to 0.852; p=0.011), but estrogen receptor beta expression was not significantly associated with progression rates. We concluded that the possibility of recurrence was low when the androgen receptor was expressed in the bladder cancer specimen and it could be the predicting factor of the stage, number of tumors, carcinoma in situ lesion and recurrence.
Prognostic value of circulating microRNAs in upper tract urinary carcinoma
Ingelmo-Torres, Mercedes; Lozano, Juan José; Capitán, David; Alcaraz, Antonio; Mengual, Lourdes
2018-01-01
The identification of upper tract urinary carcinoma (UTUC) prognostic biomarkers is urgently needed to predict tumour progression. This study aimed to identify serum microRNAs (miRNAs) that may be useful as minimally invasive predictive biomarkers of tumour progression and survival in UTUC patients. To this end, 33 UTUC patients who underwent radical nephroureterectomy at the Hospital Clinic of Barcelona were prospectively included. Expression of 800 miRNAs was evaluated in serum samples from these patients using nCounter® miRNA Expression Assays. The study was divided into an initial discovery phase (n=12) and a validation phase (n=21). Cox regression analysis was used for survival analysis. The median follow-up (range) of the series was 42 months (9-100 months). In the discovery phase, 38 differentially expressed miRNAs were identified between progressing and non-progressing UTUC patients (p<0.05). Validation of these 38 miRNAs in an independent set of UTUC patients confirmed the differential expression in 18 of them (p<0.05). Cox Regression analysis showed miR-151b and pathological stage as significant prognostic factors for tumour progression (HR=0.33, p<0.001 and HR=2.62, p=0.006, respectively) and cancer specific survival (HR=0.25, p<0.001 and HR=3.98, p=0.003, respectively). Survival curves revealed that miR-151b is able to discriminate between two groups of UTUC patients with a highly significant different probability of tumour progression (p=0.006) and cancer specific survival (p=0.034). Although the data needs to be externally validated, miRNA analysis in serum appears to be a valuable prognostic tool in UTUC patients. Particularly, differential expression of miR-151b in serum may serve as a minimally invasive prognostic tool in UTUC. PMID:29682178
Zhu, Zheng-Ming
2017-01-01
Background Urothelial Carcinoma Associated 1 (UCA1) was an originally identified lncRNA in bladder cancer. Previous studies have reported that UCA1 played a significant role in various types of cancer. This study aimed to clarify the prognostic value of UCA1 in digestive system cancers. Results The meta-analysis of 15 studies were included, comprising 1441 patients with digestive system cancers. The pooled results of 14 studies indicated that high expression of UCA1 was significantly associated with poorer OS in patients with digestive system cancers (HR: 1.89, 95 % CI: 1.52–2.26). In addition, UCA1 could be as an independent prognostic factor for predicting OS of patients (HR: 1.85, 95 % CI: 1.45–2.25). The pooled results of 3 studies indicated a significant association between UCA1 and DFS in patients with digestive system cancers (HR = 2.50; 95 % CI = 1.30–3.69). Statistical significance was also observed in subgroup meta-analysis. Furthermore, the clinicopathological values of UCA1 were discussed in esophageal cancer, colorectal cancer and pancreatic cancer. Materials and methods A comprehensive retrieval was performed to search studies evaluating the prognostic value of UCA1 in digestive system cancers. Many databases were involved, including PubMed, Web of Science, Embase and Chinese National Knowledge Infrastructure and Wanfang database. Quantitative meta-analysis was performed with standard statistical methods and the prognostic significance of UCA1 in digestive system cancers was qualified. Conclusions Elevated level of UCA1 indicated the poor clinical outcome for patients with digestive system cancers. It may serve as a new biomarker related to prognosis in digestive system cancers. PMID:28380443
Liu, Fang-Teng; Dong, Qing; Gao, Hui; Zhu, Zheng-Ming
2017-06-20
Urothelial Carcinoma Associated 1 (UCA1) was an originally identified lncRNA in bladder cancer. Previous studies have reported that UCA1 played a significant role in various types of cancer. This study aimed to clarify the prognostic value of UCA1 in digestive system cancers. The meta-analysis of 15 studies were included, comprising 1441 patients with digestive system cancers. The pooled results of 14 studies indicated that high expression of UCA1 was significantly associated with poorer OS in patients with digestive system cancers (HR: 1.89, 95 % CI: 1.52-2.26). In addition, UCA1 could be as an independent prognostic factor for predicting OS of patients (HR: 1.85, 95 % CI: 1.45-2.25). The pooled results of 3 studies indicated a significant association between UCA1 and DFS in patients with digestive system cancers (HR = 2.50; 95 % CI = 1.30-3.69). Statistical significance was also observed in subgroup meta-analysis. Furthermore, the clinicopathological values of UCA1 were discussed in esophageal cancer, colorectal cancer and pancreatic cancer. A comprehensive retrieval was performed to search studies evaluating the prognostic value of UCA1 in digestive system cancers. Many databases were involved, including PubMed, Web of Science, Embase and Chinese National Knowledge Infrastructure and Wanfang database. Quantitative meta-analysis was performed with standard statistical methods and the prognostic significance of UCA1 in digestive system cancers was qualified. Elevated level of UCA1 indicated the poor clinical outcome for patients with digestive system cancers. It may serve as a new biomarker related to prognosis in digestive system cancers.
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.
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.
Prognostic value of circulating microRNAs in upper tract urinary carcinoma.
Montalbo, Ruth; Izquierdo, Laura; Ingelmo-Torres, Mercedes; Lozano, Juan José; Capitán, David; Alcaraz, Antonio; Mengual, Lourdes
2018-03-30
The identification of upper tract urinary carcinoma (UTUC) prognostic biomarkers is urgently needed to predict tumour progression. This study aimed to identify serum microRNAs (miRNAs) that may be useful as minimally invasive predictive biomarkers of tumour progression and survival in UTUC patients. To this end, 33 UTUC patients who underwent radical nephroureterectomy at the Hospital Clinic of Barcelona were prospectively included. Expression of 800 miRNAs was evaluated in serum samples from these patients using nCounter® miRNA Expression Assays. The study was divided into an initial discovery phase (n=12) and a validation phase (n=21). Cox regression analysis was used for survival analysis. The median follow-up (range) of the series was 42 months (9-100 months). In the discovery phase, 38 differentially expressed miRNAs were identified between progressing and non-progressing UTUC patients (p<0.05). Validation of these 38 miRNAs in an independent set of UTUC patients confirmed the differential expression in 18 of them (p<0.05). Cox Regression analysis showed miR-151b and pathological stage as significant prognostic factors for tumour progression (HR=0.33, p<0.001 and HR=2.62, p=0.006, respectively) and cancer specific survival (HR=0.25, p<0.001 and HR=3.98, p=0.003, respectively). Survival curves revealed that miR-151b is able to discriminate between two groups of UTUC patients with a highly significant different probability of tumour progression (p=0.006) and cancer specific survival (p=0.034). Although the data needs to be externally validated, miRNA analysis in serum appears to be a valuable prognostic tool in UTUC patients. Particularly, differential expression of miR-151b in serum may serve as a minimally invasive prognostic tool in UTUC.
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.
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
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.
Prognostic nomogram for previously untreated adult patients with acute myeloid leukemia
Zheng, Zhuojun; Li, Xiaodong; Zhu, Yuandong; Gu, Weiying; Xie, Xiaobao; Jiang, Jingting
2016-01-01
This study was designed to perform an acceptable prognostic nomogram for acute myeloid leukemia. The clinical data from 311 patients from our institution and 165 patients generated with Cancer Genome Atlas Research Network were reviewed. A prognostic nomogram was designed according to the Cox's proportional hazard model to predict overall survival (OS). To compare the capacity of the nomogram with that of the current prognostic system, the concordance index (C-index) was used to validate the accuracy as well as the calibration curve. The nomogram included 6 valuable variables: age, risk stratifications based on cytogenetic abnormalities, status of FLT3-ITD mutation, status of NPM1 mutation, expression of CD34, and expression of HLA-DR. The C-indexes were 0.71 and 0.68 in the primary and validation cohort respectively, which were superior to the predictive capacity of the current prognostic systems in both cohorts. The nomogram allowed both patients with acute myeloid leukemia and physicians to make prediction of OS individually prior to treatment. PMID:27689396
van der Zee, J A; van Eijck, C H J; Hop, W C J; van Dekken, H; Dicheva, B M; Seynhaeve, A L B; Koning, G A; Eggermont, A M M; Ten Hagen, T L M
2012-11-01
Pancreatic cancer has a dismal prognosis. Attempts have been made to improve outcome by several 5-FU based adjuvant treatment regimens. However, the results are conflicting. There seems to be a continental divide with respect to the use of 5-FU based chemoradiotherapy (CRT). Furthermore, evidence has been presented showing a different response of pancreatic head and periampullary cancer to 5-FU based CRT. Expression of thymidylate synthase (TS) has been associated with improved outcome following 5-FU based adjuvant treatment in gastrointestinal cancer. This prompted us to determine the differential expression and prognostic value of TS in pancreatic head and periampullary cancer. TS protein expression was studied by immunohistochemistry on original paraffin embedded tissue from 212 patients following microscopic radical resection (R0) of pancreatic head (n = 98) or periampullary cancer (n = 114). Expression was investigated for associations with recurrence free (RFS), cancer specific (CSS) and overall survival (OS), and conventional prognostic factors. High cytosolic TS expression was present in 26% of pancreatic head tumours and 37% of periampullary tumours (p = .11). Furthermore, TS was an independent factor predicting favourable outcome following curative resection of pancreatic head cancer (p = .003, .001 and .001 for RFS, CSS and OS, respectively). In contrast, in periampullary cancer, TS was not associated with outcome (all p > .10). TS, was found to be poorly expressed in both pancreatic head and periampullary cancer and identified as an independent prognostic factor following curative resection of pancreatic head cancer. Copyright © 2012 Elsevier Ltd. All rights reserved.
Omland, Torbjørn; White, Harvey D
2017-01-01
Multiple circulating biomarkers have been associated with the incidence of cardiovascular events and proposed as potential tools for risk stratification in stable ischemic heart disease (IHD), yet current guidelines do not make any firm recommendations concerning the use of biomarkers for risk stratification in this setting. This state-of-the-art review provides an overview of biomarkers for risk stratification in stable IHD. Circulating biomarkers associated with the risk of cardiovascular events in patients with stable IHD reflect different pathophysiological processes, including myocardial injury, myocardial stress and remodeling, metabolic status, vascular inflammation, and oxidative stress. Compared to the primary prevention setting, biomarkers reflecting end-organ damage and future risk of heart failure development and cardiovascular death may play more important roles in the stable IHD setting. Accordingly, biomarkers that reflect chronic, low-grade myocardial injury, and stress, i.e., high-sensitivity cardiac troponins and natriuretic peptides, provide graded and incremental prognostic information to conventional risk markers. In contrast, in stable IHD patients the prognostic value of traditional metabolic biomarkers, including serum lipids, is limited. Among several novel biomarkers, growth-differentiation factor-15 may provide the most robust prognostic information, whereas most inflammatory markers provide limited incremental prognostic information to risk factor models that include conventional risk factors, natriuretic peptides, and high-sensitivity troponins. Circulating biomarkers hold promise as useful tools for risk stratification in stable IHD, but their future incorporation into clinically useful risk scores will depend on prospective, rigorously performed clinical trials that document enhanced risk prediction. © 2016 American Association for Clinical Chemistry.
Yan, Weiwei; Zhu, Zhenyu; Pan, Fei; Huang, Ang; Dai, Guang-Hai
2018-01-01
To explore new biomarkers for indicating the recurrence and prognosis in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients after tumor resection, we investigated the expression and prognostic value of c-kit(CD117) in HBV-related HCC. Immunohistochemistry was used to estimate the expression of c-kit(CD117) and CD34 in the liver cancer tissues. The correlations between the expression of these biomarkers and the clinicopathologic characteristics were analyzed. The positive rate of c-kit(CD117) expression in 206 HCC cases was 48.1%, and c-kit expression was significantly related with CD34-positive microvessel density. CD34-microvessel density numbers were much higher in c-kit(+) HCC tissues than in c-kit(-) HCC tissues (44.13±17.01 vs 26.87±13.16, P =0.003). The expression of c-kit was significantly higher in patients with Edmondson grade III-IV ( P <0.001) and TNM stage III ( P <0.001). Moreover, Kaplan-Meier survival analysis showed that c-kit ( P <0.001) expression was correlated with reduced disease-free survival (DFS). Multivariate analysis identified c-kit as an independent poor prognostic factor of DFS in HCC patients ( P <0.001). Increased c-kit expression could be considered as an independent unfavorable prognostic factor for predicting DFS in HBV-related HCC patients after surgery. These results could be used to identify patients at a higher risk of early tumor recurrence and poor prognosis.
Current state of prognostication and risk stratification in myelodysplastic syndromes.
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.
Breast cancer: integrating the patient with her genome.
Angrist, Misha
2005-01-01
Increasingly, gene expression data are becoming the currency of the realm in assessing disease prognosis. This has been especially evident in cancer, particularly those malignancies for which tumor samples are fairly accessible and understanding prognostic factors has clear implications for treatment decisions. Recently, Pittman et al. demonstrated substantially increased accuracy of personalized disease outcome prediction in breast cancer by integrating gene-expression profile data with traditional clinical risk factors in a set of 158 breast cancer patients.
Mdah, Wahid; Mzalbat, Raneen; Gilbey, Peter; Stein, Moshe; Sharabi, Adi; Zidan, Jamal
2014-11-01
Human epidermal growth factor receptor 2 (HER-2) is a well recognized prognostic and predictive factor in breast cancer. However, the role of HER-2 in thyroid cancer remains controversial. The aim of this study was to evaluate HER-2 expression in differentiated thyroid cancer (DTC) and determine whether there is an association with other clinical and pathological characteristics. A total of 69 patients with DTC were investigated, 58 of whom had papillary and 11 follicular carcinomas. HER-2 was detected by immunohistochemical examination on sections from formalin-fixed, paraffin-embedded tumor tissues. Tumors with HER-2 expression classed as +1 and +2 were retested with chromogenic in situ hybridization. Clinicopathological data were retrieved from the hospital records of the patients. HER-2 overexpression was found in 4 (6.9%) of the 58 patients with papillary carcinoma, whereas there was no HER-2 overexpression in any of the 11 cases of follicular carcinoma. There was no association of HER-2 expression with tumor size, pathological grade and cervical lymph node metastasis. In conclusion, there were no HER-2 positive cases of follicular carcinoma and the incidence of HER-2 overexpression in papillary carcinoma was very low. Thus, HER-2 cannot be used routinely as a prognostic or predictive factor in DTC. The expression of other epidermal growth factor receptors in DTC merits further investigation.
Tumor budding as a novel predictor of occult metastasis in cT2N0 tongue squamous cell carcinoma.
Sakata, Junki; Yamana, Keisuke; Yoshida, Ryoji; Matsuoka, Yuichiro; Kawahara, Kenta; Arita, Hidetaka; Nakashima, Hikaru; Nagata, Masashi; Hirosue, Akiyuki; Kawaguchi, Sho; Gohara, Shunsuke; Nagao, Yuka; Hiraki, Akimitsu; Shinohara, Masanori; Toya, Ryo; Murakami, Ryuji; Nakayama, Hideki
2018-06-01
Occult neck metastasis is an important prognostic factor in patients with tongue squamous cell carcinoma (TSCC) who are deemed clinically negative for neck metastasis. The purpose of this study was to identify predictive factors for occult neck metastasis arising from TSCC and to determine patient prognosis. Ninety-seven patients with cT2N0 TSCC who underwent surgical resection of their primary lesion as initial therapy were enrolled in this retrospective study. Cutoff values for depth of invasion (≥3.3 mm) and the tumor budding score (≥4) were determined using receiver operator characteristic analyses. Univariate and multivariate analyses revealed that a tumor budding score ≥4 is a significant independent predictive factor for the occurrence of occult neck metastasis, which in turn is a significant independent prognostic factor. When evaluating tumor budding, we demonstrated greater interobserver and intraobserver agreement when using immunohistochemical staining for cytokeratin AE1/AE3 than with hematoxylin and eosin staining (HE). We conclude that the evaluation of tumor budding is effective for identifying populations at high risk of occult neck metastasis, which will enable the planning of appropriate therapeutic strategies for patients with cT2N0 TSCC. Furthermore, cytokeratin staining is recommended over HE staining for simpler and more accurate evaluation of tumor budding. Copyright © 2018 Elsevier Inc. All rights reserved.
Shek, L L; Godolphin, W
1988-10-01
The independent prognostic effects of certain clinical and pathological variables measured at the time of primary diagnosis were assessed with Cox multivariate regression analysis. The 859 patients with primary breast cancer, on which the proportional hazards model was based, had a median follow-up of 60 months. Axillary nodal status (categorized as N0, N1-3 or N4+) was the most significant and independent factor in overall survival, but inclusion of TNM stage, estrogen receptor (ER) concentration and tumor necrosis significantly improved survival predictions. Predictions made with the model showed striking subset survival differences within stage: 5-year survival from 36% (N4+, loge[ER] = 0, marked necrosis) to 96% (N0, loge[ER] = 6, no necrosis) in TNM I, and from 0 to 70% for the same categories in TNM IV. Results of the model were used to classify patients into four distinct risk groups according to a derived hazard index. An 8-fold variation in survival was seen with the highest (greater than 3) to lowest index values (less than 1). Each hazard index level included patients with varied combinations of the above factors, but could be considered to denote the same degree of risk of breast cancer mortality. A model with ER concentration, nodal status, and tumor necrosis was found to best predict survival after disease recurrence in 369 patients, thus confirming the enduring biological significance of these factors.
Signorini, Giulia; Dagani, Jessica; Bulgari, Viola; Ferrari, Clarissa; de Girolamo, Giovanni
2016-01-01
Accurate prognosis is an essential aspect of good clinical practice and efficient health services, particularly for chronic and disabling diseases, as in geriatric populations. This study aims to examine the accuracy of clinical prognostic predictions and to devise prediction models combining clinical variables and clinicians' prognosis for a geriatric patient sample. In a sample of 329 consecutive older patients admitted to 10 geriatric units, we evaluated the accuracy of clinicians' prognosis regarding three outcomes at discharge: global functioning, length of stay (LoS) in hospital, and destination at discharge (DD). A comprehensive set of sociodemographic, clinical, and treatment-related information were also collected. Moderate predictive performance was found for all three outcomes: area under receiver operating characteristic curve of 0.79 and 0.78 for functioning and LoS, respectively, and moderate concordance, Cohen's K = 0.45, between predicted and observed DD. Predictive models found the Blaylock Risk Assessment Screening Score together with clinicians' judgment relevant to improve predictions for all outcomes (absolute improvement in adjusted and pseudo-R(2) up to 19%). Although the clinicians' estimates were important factors in predicting global functioning, LoS, and DD, more research is needed regarding both methodological aspects and clinical measurements, to improve prognostic clinical indices. Copyright © 2016 Elsevier Inc. All rights reserved.
Independent Prognostic Factors for Acute Organophosphorus Pesticide Poisoning.
Tang, Weidong; Ruan, Feng; Chen, Qi; Chen, Suping; Shao, Xuebo; Gao, Jianbo; Zhang, Mao
2016-07-01
Acute organophosphorus pesticide poisoning (AOPP) is becoming a significant problem and a potential cause of human mortality because of the abuse of organophosphate compounds. This study aims to determine the independent prognostic factors of AOPP by using multivariate logistic regression analysis. The clinical data for 71 subjects with AOPP admitted to our hospital were retrospectively analyzed. This information included the Acute Physiology and Chronic Health Evaluation II (APACHE II) scores, 6-h post-admission blood lactate levels, post-admission 6-h lactate clearance rates, admission blood cholinesterase levels, 6-h post-admission blood cholinesterase levels, cholinesterase activity, blood pH, and other factors. Univariate analysis and multivariate logistic regression analyses were conducted to identify all prognostic factors and independent prognostic factors, respectively. A receiver operating characteristic curve was plotted to analyze the testing power of independent prognostic factors. Twelve of 71 subjects died. Admission blood lactate levels, 6-h post-admission blood lactate levels, post-admission 6-h lactate clearance rates, blood pH, and APACHE II scores were identified as prognostic factors for AOPP according to the univariate analysis, whereas only 6-h post-admission blood lactate levels, post-admission 6-h lactate clearance rates, and blood pH were independent prognostic factors identified by multivariate logistic regression analysis. The receiver operating characteristic analysis suggested that post-admission 6-h lactate clearance rates were of moderate diagnostic value. High 6-h post-admission blood lactate levels, low blood pH, and low post-admission 6-h lactate clearance rates were independent prognostic factors identified by multivariate logistic regression analysis. Copyright © 2016 by Daedalus Enterprises.
Lee, Sang-Eun; Cho, Iksung; Hong, Geu-Ru; Sung, Ji Min; Cho, In-Jeong; Shim, Chi Young; Choi, Byoung Wook; Chung, Namsik
2015-01-01
Background To explore the prognostic performance of coronary computed tomography angiography (CCTA) and exercise electrocardiography (XECG) in asymptomatic subjects. Methods We retrospectively enrolled 812 (59 ± 9 years, 60.8% male) asymptomatic subjects who underwent CCTA and XECG concurrently from 2003 through 2009. Subjects were followed-up for major adverse cardiac events (MACE) including cardiac death, nonfatal myocardial infarction, unstable angina, and revascularization after 90 days from index CCTA. Results The prevalence of occult coronary artery disease (CAD) detected by CCTA was 17.5% and 120 subjects (14.8%) had positive XECG. During a mean follow-up of 37 ± 16 months, nine subjects experienced MACE. In multivariable Cox-regression analysis, only the presence of CAD by CCTA independently predicted future MACE (p = 0.002). Moreover, CAD by CCTA improved the predictive value when added to a clinical risk factor model using the likelihood ratio test (p < 0.001). Notably, the prognostic value of CCTA persisted in the moderate-to-high-risk group as classified by the Duke treadmill score (p = 0.040), but not in the low-risk group (p = 0.991). Conclusion CCTA provides incremental prognostic benefit over and above XECG in an asymptomatic population, especially for those in a moderate-to-high-risk group as classified by the Duke treadmill score. Risk stratification using XECG may prove valuable for identifying asymptomatic subjects who can benefit from CCTA. PMID:26755933
Bisarro Dos Reis, Mariana; Barros-Filho, Mateus Camargo; Marchi, Fábio Albuquerque; Beltrami, Caroline Moraes; Kuasne, Hellen; Pinto, Clóvis Antônio Lopes; Ambatipudi, Srikant; Herceg, Zdenko; Kowalski, Luiz Paulo; Rogatto, Silvia Regina
2017-11-01
Even though the majority of well-differentiated thyroid carcinoma (WDTC) is indolent, a number of cases display an aggressive behavior. Cumulative evidence suggests that the deregulation of DNA methylation has the potential to point out molecular markers associated with worse prognosis. To identify a prognostic epigenetic signature in thyroid cancer. Genome-wide DNA methylation assays (450k platform, Illumina) were performed in a cohort of 50 nonneoplastic thyroid tissues (NTs), 17 benign thyroid lesions (BTLs), and 74 thyroid carcinomas (60 papillary, 8 follicular, 2 Hürthle cell, 1 poorly differentiated, and 3 anaplastic). A prognostic classifier for WDTC was developed via diagonal linear discriminant analysis. The results were compared with The Cancer Genome Atlas (TCGA) database. A specific epigenetic profile was detected according to each histological subtype. BTLs and follicular carcinomas showed a greater number of methylated CpG in comparison with NTs, whereas hypomethylation was predominant in papillary and undifferentiated carcinomas. A prognostic classifier based on 21 DNA methylation probes was able to predict poor outcome in patients with WDTC (sensitivity 63%, specificity 92% for internal data; sensitivity 64%, specificity 88% for TCGA data). High-risk score based on the classifier was considered an independent factor of poor outcome (Cox regression, P < 0.001). The methylation profile of thyroid lesions exhibited a specific signature according to the histological subtype. A meaningful algorithm composed of 21 probes was capable of predicting the recurrence in WDTC. Copyright © 2017 Endocrine Society
Artac, Mehmet; Bozcuk, Hakan; Kiyici, Aysel; Eren, Orhan Onder; Boruban, Melih Cem; Ozdogan, Mustafa
2013-04-01
Our objective was to determine whether serum leptin levels and obesity-related factors could affect outcome for metastatic breast cancer (MBC) patients treated with aromatase inhibitors (AIs). Sixty MBC patients treated with first line hormonal therapy were enrolled in this study. Median age was 51 years (range 28-75). Median leptin level was 19400 pg/ml (1970-91900) and estradiol level 29.6 pg/ml (4.0-181.9). Factors associated with overall survival in univariate analysis were age and waist-to-hip ratio (WHR), whereas only WHR retained significance in the multivariate analysis. However, no factor was associated with progression-free survival. However, WHR was found to be a significant prognostic marker only if the leptin level was ≥19400 pg/ml (HR = 0.38; 95% CI: 0.16-0.91). This study suggests that serum leptin levels and WHR together may serve as potential prognostic markers in MBC patients treated with AIs.
Bourdel-Marchasson, Isabelle; Diallo, Abou; Bellera, Carine; Blanc-Bisson, Christelle; Durrieu, Jessica; Germain, Christine; Mathoulin-Pélissier, Simone; Soubeyran, Pierre; Rainfray, Muriel; Fonck, Mariane; Doussau, Adelaïde
2016-01-01
The MNA (Mini Nutritional Assessment) is known as a prognosis factor in older population. We analyzed the prognostic value for one-year mortality of MNA items in older patients with cancer treated with chemotherapy as the basis of a simplified prognostic score. The prospective derivation cohort included 606 patients older than 70 years with an indication of chemotherapy for cancers. The endpoint to predict was one-year mortality. The 18 items of the Full MNA, age, gender, weight loss, cancer origin, TNM, performance status and lymphocyte count were considered to construct the prognostic model. MNA items were analyzed with a backward step-by-step multivariate logistic regression and other items were added in a forward step-by-step regression. External validation was performed on an independent cohort of 229 patients. At one year 266 deaths had occurred. Decreased dietary intake (p = 0.0002), decreased protein-rich food intake (p = 0.025), 3 or more prescribed drugs (p = 0.023), calf circumference <31 cm (p = 0.0002), tumor origin (p<0.0001), metastatic status (p = 0.0007) and lymphocyte count <1500/mm3 (0.029) were found to be associated with 1-year mortality in the final model and were used to construct a prognostic score. The area under curve (AUC) of the score was 0.793, which was higher than the Full MNA AUC (0.706). The AUC of the score in validation cohort (229 subjects, 137 deaths) was 0.698. Key predictors of one-year mortality included cancer cachexia clinical features, comorbidities, the origin and the advanced status of the tumor. The prognostic value of this model combining a subset of MNA items and cancer related items was better than the full MNA, thus providing a simple score to predict 1-year mortality in older patients with an indication of chemotherapy.
Prognostic significance of INF-induced transmembrane protein 1 in colorectal cancer.
He, Jingdong; Li, Jin; Feng, Wanting; Chen, Longbang; Yang, Kangqun
2015-01-01
Interferon-induced transmembrane protein 1 (IFITM1) has recently been implicated in tumorigenesis. However, the prognostic value of IFITM1 in colorectal cancer remains unknown. The present study aimed to examine the expression and prognostic significance of IFITM1 in human colorectal cancer. IFITM1 expression was analyzed in 144 archived, paraffin-embedded colorectal cancer tissues and corresponding normal colorectal mucosa by immunohistochemistry. The correlation of IFITM1 with clinic-pathological features and overall survival of colorectal cancer patients was evaluated. IFITM1 was overexpressed in colonic cancer tissues but not in rectal cancer tissues, compared to control normal tissues. The expression of IFITM1 was significantly higher in patients with poor differentiation (P=0.031). The patients with higher IFITM1 expression had worse overall survival outcomes than those with lower IFITM1 expression in rectal cancer (P=0.037). Univariate Cox regression suggested that older age and poorly differentiation status predict shorter overall survival in colorectal cancer (P<0.05). However, IFITM1 expression was not a significant prognostic factor for survival by univariate or multivariate analyses. In conclusion, high expression of IFITM1 is associated with poor prognosis of rectal cancer. IFITM1 may serve as an independent prognostic biomarker for colorectal cancer.
NASA Technical Reports Server (NTRS)
Celaya, Jose; Kulkarni, Chetan; Biswas, Gautam; Saha, Sankalita; Goebel, Kai
2011-01-01
A remaining useful life prediction methodology for electrolytic capacitors is presented. This methodology is based on the Kalman filter framework and an empirical degradation model. Electrolytic capacitors are used in several applications ranging from power supplies on critical avionics equipment to power drivers for electro-mechanical actuators. These devices are known for their comparatively low reliability and given their criticality in electronics subsystems they are a good candidate for component level prognostics and health management. Prognostics provides a way to assess remaining useful life of a capacitor based on its current state of health and its anticipated future usage and operational conditions. We present here also, experimental results of an accelerated aging test under electrical stresses. The data obtained in this test form the basis for a remaining life prediction algorithm where a model of the degradation process is suggested. This preliminary remaining life prediction algorithm serves as a demonstration of how prognostics methodologies could be used for electrolytic capacitors. In addition, the use degradation progression data from accelerated aging, provides an avenue for validation of applications of the Kalman filter based prognostics methods typically used for remaining useful life predictions in other applications.
NASA Technical Reports Server (NTRS)
Celaya, Jose R.; Kulkarni, Chetan S.; Biswas, Gautam; Goebel, Kai
2012-01-01
A remaining useful life prediction methodology for electrolytic capacitors is presented. This methodology is based on the Kalman filter framework and an empirical degradation model. Electrolytic capacitors are used in several applications ranging from power supplies on critical avionics equipment to power drivers for electro-mechanical actuators. These devices are known for their comparatively low reliability and given their criticality in electronics subsystems they are a good candidate for component level prognostics and health management. Prognostics provides a way to assess remaining useful life of a capacitor based on its current state of health and its anticipated future usage and operational conditions. We present here also, experimental results of an accelerated aging test under electrical stresses. The data obtained in this test form the basis for a remaining life prediction algorithm where a model of the degradation process is suggested. This preliminary remaining life prediction algorithm serves as a demonstration of how prognostics methodologies could be used for electrolytic capacitors. In addition, the use degradation progression data from accelerated aging, provides an avenue for validation of applications of the Kalman filter based prognostics methods typically used for remaining useful life predictions in other applications.
A Comparison of Systemic Inflammation-Based Prognostic Scores in Patients on Regular Hemodialysis
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
Prognostic significance of thymidylate synthase (TS) expression in cutaneous malignant melanoma.
Shimizu, A; Kaira, K; Yasuda, M; Asao, T; Ishikawa, O
2016-01-01
Thymidylate synthase (TS) plays an essential role in the pathogenesis and development of cancer, and TS-targeting agents have been widely used against different types of cancers. However, it remains still unclear whether or not TS is expressed in malignant melanoma. We conducted the clinicopathological study to investigate the prognostic significance of TS expression in cutaneous malignant melanoma. Ninety-nine patients with surgically resected cutaneous malignant melanoma were assessed. Tumor sections were stained by immunohistochemistry for TS, Ki-67, and microvessel density (MVD) determined by CD34. TS was positively expressed in 26% (26 out of 99). The expression of TS was significantly associated with T factor, cell proliferation (Ki-67) and MVD (CD34). By Spearman's rank test, TS expression was significantly correlated with Ki67 and CD34. By univariate analysis, ulceration, disease stage, TS, Ki-67 and CD34 had a significant relationship with survival. Multivariate analysis confirmed that TS was an independent prognostic factor for poor prognosis of cutaneous malignant melanoma. The positive expression of TS could be a useful marker for predicting poor prognosis in patients with cutaneous malignant melanoma, and TS-targeting agents may be worth trying for the treatment of this dismal disease.
Nikiphorou, Elena; Carpenter, Lewis; Norton, Sam; Morris, Stephen; MacGregor, Alex; Dixey, Josh; Williams, Peter; Kiely, Patrick; Walsh, David Andrew; Young, Adam
2017-03-01
The structural damage caused by rheumatoid arthritis (RA) can often be mitigated by orthopaedic surgery in late disease. This study evaluates the value of predictive factors for orthopaedic intervention. A systematic review of literature was undertaken to identify papers describing predictive factors for orthopaedic surgery in RA. Manuscripts were selected if they met inclusion criteria of cohort study design, diagnosis of RA, follow-up duration/disease duration ≥3 years, any orthopaedic surgical interventions recorded, and then summarised for predictive factors. A separate predictive analysis was performed on two consecutive UK Early RA cohorts, linked to national datasets. The literature search identified 15 reports examining predictive factors for orthopaedic intervention, 4 inception, 5 prospective and 6 retrospective. Despite considerable variation, acute phase, x-ray scores, women and genotyping were the most commonly reported prognostic markers. The current predictive analysis included 1602 procedures performed in 711 patients (25-year cumulative incidence 26%). Earlier recruitment year, erosions and lower haemoglobin predicted both intermediate and major surgery (P<0.05). Studies report variations in type of and predictive power of clinical and laboratory parameters for different surgical interventions suggesting specific contributions from different pathological and/or patient-level factors. Our current analysis suggests that attention to non-inflammatory factors in addition to suppression of inflammation is needed to minimise the burden of orthopaedic surgery.
Jing, Chu-Yu; Fu, Yi-Peng; Zheng, Su-Su; Yi, Yong; Shen, Hu-Jia; Huang, Jin-Long; Xu, Xin; Lin, Jia-Jia; Zhou, Jian; Fan, Jia; Ren, Zheng-Gang; Qiu, Shuang-Jian; Zhang, Bo-Heng
2017-01-01
Abstract Adjuvant transarterial chemoembolization (TACE) is a major option for postoperative hepatocellular carcinoma (HCC) patients with recurrence risk factors. However, individualized predictive models for subgroup of these patients are limited. This study aimed to develop a prognostic nomogram for patients with HCC underwent adjuvant TACE following curative resection. A cohort comprising 144 HCC patients who received adjuvant TACE following curative resection in the Zhongshan Hospital were analyzed. The nomogram was formulated based on independent prognostic indicators for overall survival (OS). The performance of the nomogram was evaluated by the concordance index (C-index), calibration curve, and decision curve analysis (DCA) and compared with the conventional staging systems. The results were validated in an independent cohort of 86 patients with the same inclusion criteria. Serum alpha-fetoprotein (AFP), hyper-sensitive C-reactive protein (hs-CRP), incomplete tumor encapsulation, and double positive staining of Cytokeratin 7 and Cytokeratin 19 on tumor cells were identified as independent predictors for OS. The C-indices of the nomogram for OS prediction in the training cohort and validation cohort were 0.787 (95%CI 0.775–0.799) and 0.714 (95%CI 0.695–0.733), respectively. In both the training and validation cohorts, the calibration plot showed good consistency between the nomogram-predicted and the observed survival. Furthermore, the established nomogram was superior to the conventional staging systems in terms of C-index and clinical net benefit on DCA. The proposed nomogram provided an accurate prediction on risk stratification for HCC patients underwent adjuvant TACE following curative resection. PMID:28296727
ERIC Educational Resources Information Center
Poll, Gerard H.; Burke, Lisa; Miller, Carol A.; Fiene, Judy
2017-01-01
Prognostic statements are a standard component of assessments for adolescents at risk for language-learning disabilities, but there is limited evidence on the validity of prognostic indicators. In two studies, we collected measures of language ability and candidate prognostic indicators from adolescents age 12 to 13. We conducted an expository…
Li, Ya-Jun; Li, Zhi-Ming; Xia, Yi; Huang, Jia-Jia; Huang, Hui-Qiang; Xia, Zhong-Jun; Lin, Tong-Yu; Li, Su; Cai, Xiu-Yu; Wu-Xiao, Zhi-Jun; Jiang, Wen-Qi
2013-01-01
C-reactive protein (CRP) is a biomarker of the inflammatory response, and it shows significant prognostic value for several types of solid tumors. The prognostic significance of CRP for lymphoma has not been fully examined. We evaluated the prognostic role of baseline serum CRP levels in patients with extranodal natural killer (NK)/T-cell lymphoma (ENKTL). We retrospectively analyzed 185 patients with newly diagnosed ENKTL. The prognostic value of the serum CRP level was evaluated for the low-CRP group (CRP≤10 mg/L) versus the high-CRP group (CRP>10 mg/L). The prognostic value of the International Prognostic Index (IPI) and the Korean Prognostic Index (KPI) were evaluated and compared with the newly developed prognostic model. Patients in the high-CRP group tended to display increased adverse clinical characteristics, lower rates of complete remission (P<0.001), inferior progression-free survival (PFS, P = 0.001), and inferior overall survival (OS, P<0.001). Multivariate analysis demonstrated that elevated serum CRP levels, age >60 years, hypoalbuminemia, and elevated lactate dehydrogenase levels were independent adverse predictors of OS. Based on these four independent predictors, we constructed a new prognostic model that identified 4 groups with varying OS: group 1, no adverse factors; group 2, 1 factor; group 3, 2 factors; and group 4, 3 or 4 factors (P<0.001). The novel prognostic model was found to be superior to both the IPI in discriminating patients with different outcomes in the IPI low-risk group and the KPI in distinguishing between the low- and intermediate-low-risk groups, the intermediate-low- and high-intermediate-risk groups, and the high-intermediate- and high-risk groups. Our results suggest that pretreatment serum CRP levels represent an independent predictor of clinical outcome for patients with ENKTL. The prognostic value of the new prognostic model is superior to both IPI and KPI.
Xia, Yi; Huang, Jia-Jia; Huang, Hui-Qiang; Xia, Zhong-Jun; Lin, Tong-Yu; Li, Su; Cai, Xiu-Yu; Wu-Xiao, Zhi-Jun; Jiang, Wen-Qi
2013-01-01
Background C-reactive protein (CRP) is a biomarker of the inflammatory response, and it shows significant prognostic value for several types of solid tumors. The prognostic significance of CRP for lymphoma has not been fully examined. We evaluated the prognostic role of baseline serum CRP levels in patients with extranodal natural killer (NK)/T-cell lymphoma (ENKTL). Methods We retrospectively analyzed 185 patients with newly diagnosed ENKTL. The prognostic value of the serum CRP level was evaluated for the low-CRP group (CRP≤10 mg/L) versus the high-CRP group (CRP>10 mg/L). The prognostic value of the International Prognostic Index (IPI) and the Korean Prognostic Index (KPI) were evaluated and compared with the newly developed prognostic model. Results Patients in the high-CRP group tended to display increased adverse clinical characteristics, lower rates of complete remission (P<0.001), inferior progression-free survival (PFS, P = 0.001), and inferior overall survival (OS, P<0.001). Multivariate analysis demonstrated that elevated serum CRP levels, age >60 years, hypoalbuminemia, and elevated lactate dehydrogenase levels were independent adverse predictors of OS. Based on these four independent predictors, we constructed a new prognostic model that identified 4 groups with varying OS: group 1, no adverse factors; group 2, 1 factor; group 3, 2 factors; and group 4, 3 or 4 factors (P<0.001). The novel prognostic model was found to be superior to both the IPI in discriminating patients with different outcomes in the IPI low-risk group and the KPI in distinguishing between the low- and intermediate-low-risk groups, the intermediate-low- and high-intermediate-risk groups, and the high-intermediate- and high-risk groups. Conclusions Our results suggest that pretreatment serum CRP levels represent an independent predictor of clinical outcome for patients with ENKTL. The prognostic value of the new prognostic model is superior to both IPI and KPI. PMID:23724031
Long Noncoding RNA HOTAIR as an Independent Prognostic Marker in Cancer: A Meta-Analysis
Yang, Guang; Gu, Fang; Li, Minrui; Zhong, Bihui; Hu, Jifan; Hoffman, Andrew; Chen, Minhu
2014-01-01
Background HOTAIR, a newly discovered long intergenic noncoding RNA (lincRNA), has been reported to be aberrantly expressed in many types of cancers. This meta-analysis summarizes its potential role as a biomarker in malignancy. Methods A quantitative meta-analysis was performed through a systematic search in Pubmed, Medline and Web of Science for eligible papers on the prognostic impact of HOTAIR in cancer from inception to Feb. 28, 2014. Pooled hazard ratios (HRs) with 95% confidence interval (95% CI) were calculated to summarize the effect. Results Nineteen studies were included in the study, with a total of 2033 patients. A significant association was observed between high HOTAIR expression and poor overall survival (OS) in patients with cancer (pooled HR 2.22, 95% CI: 1.68–2.93). Place of residence (Asian or Western countries), type of cancer (digestive or non-digestive disease), sample size (more or less than 100), and paper quality (score more or less than 85%) did not alter the significant predictive value of HOTAIR in OS from various kinds of cancer but preoperative status did. By combining HRs from Cox multivariate analyses, we found that HOTAIR expression was an independent prognostic factor for cancer patients (pooled HR 2.26, 95% CI: 1.62–3.15). Subgroup analysis showed that HOTAIR abundance was an independent prognostic factor for cancer metastasis (HR 3.90, 95% CI: 2.25–6.74). For esophageal carcinoma, high HOTAIR expression was significantly associated with TNM stage (III/IV vs. I/II: OR 6.90, 95% CI: 2.81–16.9) without heterogeneity. In gastric cancer, HOTAIR expression was found to be significantly associated with lymph node metastases (present vs. absent: OR 4.47, 95% CI: 1.88–10.63) and vessel invasion (positive vs. negative: OR 2.88, 95% CI: 1.38–6.04) without obvious heterogeneity. Conclusions HOTAIR abundance may serve as a novel predictive factor for poor prognosis in different types of cancers in both Asian and Western countries. PMID:25157956
Mackie, Fiona L; Hall, Matthew J; Morris, R Katie; Kilby, Mark D
2018-05-12
Assess ability of first trimester pregnancy related factors (ultrasound measurements, maternal characteristics, biomarkers) to predict complications in monochorionic twin pregnancies DATA SOURCES: MEDLINE, EMBASE, ISI Web of Science, CINAHL, the Cochrane Central Registration of Controlled Trials and Research Registers, and Google Scholar, from inception to 12 May 2017. Grey literature and bibliographies of articles were checked. Studies that reported ultrasound measurements, maternal characteristics, or potential biomarkers, measured in the first trimester in monochorionic diamniotic twin pregnancies, where the potential prognostic ability between the variable and twin-twin transfusion syndrome, growth restriction, or intrauterine fetal death could be assessed. Quality assessment was evaluated using the STROBE checklist by 2 reviewers independently. For meta-analysis, odds ratios using a random effects model, or standardized mean difference were calculated. If a moderate association was found, the prognostic ability was evaluated by calculating the sensitivity and specificity. Risk of heterogeneity was reported as I 2 and publication bias was visually assessed by funnel plots and quantitatively by Egger's test. Forty-eight studies were eligible for inclusion. Twenty meta-analyses could be performed. A moderate association was demonstrated in 3 meta-analyses, between: NT>95th centile in one/both fetuses and TTTS (OR 2.29 [95%CI 1.05, 4.96] I 2 =6.6%, 4 studies, 615 pregnancies); CRL discordance ≥10% and TTTS (OR 2.43 [95%CI 1.13, 5.21] I 2 =14.1%, 3 studies, 708 pregnancies); and maternal ethnicity and TTTS (OR 2.12 [95%CI 1.17, 3.83] I 2 =0.0%, 5 studies, 467 pregnancies), but none demonstrated a prognostic ability for any outcome under investigation. It is not currently possible to predict adverse outcomes in monochorionic twin pregnancies. We have revealed a lack of research investigating first trimester biomarkers in monochorionic twin pregnancies. Different assessment methods and definitions of each variable and outcome were an issue and this highlights the need for a large cohort study to evaluate these factors. Copyright © 2018 Elsevier Inc. All rights reserved.
Balasundaram, Arun Prasad; Robinson, Hilde Stendal; Vøllestad, Nina Køpke
2018-05-01
Neck pain is one of the common musculoskeletal conditions prevalent in the general population in Norway. Patients with neck pain, seek treatment from different health professionals such as general practitioners, physiotherapists, chiropractors and alternative medicine practitioners. The interventions for neck pain are typically provided in a primary care or specialised healthcare setting depending on the general practitioners' referral patterns. Clinicians are interested to know the various prognostic factors that can explain the recovery from neck pain. In order to know this, studies have explored and reported on a range of prognostic factors that contribute to the outcomes in patients with neck pain. This information is currently available only for neck pain following whiplash injury that has a traumatic origin. There is limited information on the role of prognostic factors specifically for non-specific neck pain without a traumatic episode. Moreover, there is a lack of data on whether there are interactions (moderation effects) between the prognostic factors. Therefore, we propose a hypothesis to elucidate whether the same set of prognostic factors found in neck pain associated with whiplash injuries are also identified in patients with neck pain without trauma. Additionally, we hypothesize that the association between a prognostic factor and the outcome variable (s) would be dependent on the third variable, thereby confirming the moderation effects. Clinicians could make informed decisions in the clinical management of neck pain with the knowledge of prognostic factors that explain the outcomes. It could also be used for the development of new interventions or for modifying the existing ones. Copyright © 2018 Elsevier Ltd. All rights reserved.
Yoshida, Saran; Shiozaki, Mariko; Sanjo, Makiko; Morita, Tatsuya; Hirai, Kei; Tsuneto, Satoru; Shima, Yasuo
2013-10-01
The primary end points of this analysis were to explore 1) the practices of prognostic disclosure for patients with cancer and their family members in Japan, 2) the person who decided on the degree of prognosis communication, and 3) family evaluations of the type of prognostic disclosure. Semistructured face-to-face interviews were conducted with 60 bereaved family members of patients with cancer who were admitted to palliative care units in Japan. Twenty-five percent of patients and 75% of family members were informed of the predicted survival time of the patient. Thirty-eight percent of family members answered that they themselves decided on to what degree to communicate the prognosis to patients and 83% of them chose not to disclose to patients their prognosis or incurability. In the overall evaluation of prognosis communication, 30% of the participants said that they regretted or felt doubtful about the degree of prognostic disclosure to patients, whereas 37% said that they were satisfied with the degree of prognostic disclosure and 5% said that they had made a compromise. Both in the “prognostic disclosure” group and the “no disclosure” group, there were family members who said that they regretted or felt doubtful (27% and 31%, respectively) and family members who said that they were satisfied with the degree of disclosure (27% and 44%, respectively). In conclusion, family members assume the predominant role as the decision-making source regarding prognosis disclosure to patients, and they often even prevent prognostic disclosure to patients. From the perspective of family members, any one type of disclosure is not necessarily the most acceptable choice. Future surveys should explore the reasons why family members agree or disagree with prognostic disclosures to patients and factors correlated with family evaluations.
Carrillo, José F; Carrillo, Liliana C; Cano, Ana; Ramirez-Ortega, Margarita C; Chanona, Jorge G; Avilés, Alejandro; Herrera-Goepfert, Roberto; Corona-Rivera, Jaime; Ochoa-Carrillo, Francisco J; Oñate-Ocaña, Luis F
2016-04-01
Prognostic factors in oral cavity and oropharyngeal squamous cell carcinoma (SCC) are debated. The purpose of this study was to investigate the association of prognostic factors with oncologic outcomes. Patients with oral cavity and oropharyngeal SCC treated from 1997 to 2012 were included in this retrospective cohort study. Associations of prognostic factors with locoregional recurrence (LRR) or overall survival (OS) were analyzed using the logistic regression and the Cox models. Six hundred thirty-four patients were included in this study; tumor size, surgical margins, and N classification were associated with LRR (p < .0001); considering histopathology: perineural invasion, lymphocytic infiltration, infiltrative borders, and N classification were significant determinants of LRR. Tumor size, N classification, alcoholism, and surgical margins were associated with OS (p < .0001); considering pathologic prognostic factors, perivascular invasion, islands borders, and surgical margins were independently associated with OS (p < .0001). Surgical margins, perineural and perivascular invasion, lymphocytic infiltration, and infiltrative patterns of tumor invasion are significant prognostic factors in oral cavity and oropharyngeal SCC. © 2015 Wiley Periodicals, Inc.
Tan, Xiaojie; Ding, Yibo; Luo, Yanxin; Cai, Hui; Liu, Yan; Gao, Xianhua; Liu, Qizhi; Yu, Yongwei; Du, Yan; Wang, Hao; Ma, Liye; Wang, Jianping; Chen, Kun; Ding, Yanqing; Fu, Chuangang; Cao, Guangwen
2016-01-01
Periostin (POSTN) expression in cancer cells and circulation has been related to poor prognosis of colorectal carcinoma (CRC). However, the role of POSTN expressed in intra-tumoral stroma on CRC progression remains largely unknown. This study enrolled 1098 CRC patients who received surgical treatment in Shanghai and Guangzhou, Mainland China. In Shanghai cohort, immunohistochemistry score of stromal POSTN expression increased consecutively from adjacent mucosa, primary CRC tissues, to metastatic CRC tissues (P < 0.001), while medium- and high-stromal POSTN expression, rather than epithelial POSTN expression, independently predicted unfavorable prognoses of CRC, adjusted for covariates including TNM stage and postoperative chemotherapy in multivariate Cox models. The results in Shanghai cohort were faithfully replicated in Guangzhou cohort. Stromal POSTN expression dose-dependently predicted an unfavorable prognosis of stage III CRC patients with postoperative chemotherapy in both cohorts. POSTN derived from colonic fibroblasts or recombinant POSTN significantly promoted proliferation, anchorage independent growth, invasion, and chemo-resistance of CRC cells; whereas these effects were counteracted via targeting to PI3K/Akt or Wnt/β-catenin signaling pathway. CRC cell RKO-derived factor(s) significantly induced POSTN production in colonic fibroblasts and autocrine POSTN promoted proliferation, migration, and anchorage independent growth of fibroblasts. Conclusively, stromal POSTN is prognostic and predictive for CRC via creating a niche to facilitate cancer progression. Targeting POSTN-induced signaling pathways may be therapeutic options for metastatic or chemoresistant CRC. PMID:26556874
Zapater, E; Moreno, S; Fortea, M A; Campos, A; Armengot, M; Basterra, J
2000-11-01
Many studies have investigated prognostic factors in laryngeal carcinoma, with sometimes conflicting results. Apart from the importance of environmental factors, the different statistical methods employed may have influenced such discrepancies. A program based on artificial intelligence techniques is designed to determine the prognostic factors in a series of 122 laryngeal carcinomas. The results obtained are compared with those derived from two classical statistical methods (Cox regression and mortality tables). Tumor location was found to be the most important prognostic factor by all methods. The proposed intelligent system is found to be a sound method capable of detecting exceptional cases.
Yao, Zong-Han; Liao, Wei-Yu; Ho, Chao-Chi; Chen, Kuan-Yu; Shih, Jin-Yuan; Chen, Jin-Shing; Lin, Zhong-Zhe; Lin, Chia-Chi; Chih-Hsin Yang, James; Yu, Chong-Jen
2017-09-01
This study aimed to identify independent prognostic factors for overall survival (OS) of patients with advanced non-small cell lung cancer (NSCLC) harboring an activating epidermal growth factor receptor (EGFR) mutation and receiving gefitinib as first-line treatment in real-world practice. We enrolled 226 patients from June 2011 to May 2013. During this period, gefitinib was the only EGFR-tyrosine kinase inhibitor reimbursed by the Bureau of National Health Insurance of Taiwan. The median progression-free survival and median OS were 11.9 months (95% confidence interval [CI]: 9.7-14.2) and 26.9 months (21.2-32.5), respectively. The Cox proportional hazards regression model revealed that postoperative recurrence, performance status (Eastern Cooperative Oncology Grade [ECOG] ≥2), smoking index (≥20 pack-years), liver metastasis at initial diagnosis, and chronic hepatitis C virus (HCV) infection were independent prognostic factors for OS (hazard ratio [95% CI] 0.3 [0.11-0.83], p = .02; 2.69 [1.60-4.51], p < .001; 1.92 [1.24-2.97], p = .003; 2.26 [1.34-3.82], p = .002; 3.38 [1.85-7.78], p < .001, respectively). However, brain metastasis (BM) at initial diagnosis or intracranial progression during gefitinib treatment had no impact on OS (1.266 [0.83-1.93], p = .275 and 0.75 [0.48-1.19], p = .211, respectively). HCV infection, performance status (ECOG ≥2), newly diagnosed advanced NSCLC without prior operation, and liver metastasis predicted poor OS in EGFR mutation-positive advanced NSCLC patients treated with first-line gefitinib; however, neither BM at initial diagnosis nor intracranial progression during gefitinib treatment had an impact on OS. The finding that chronic hepatitis C virus (HCV) infection might predict poor overall survival (OS) in epidermal growth factor receptor mutation-positive advanced non-small cell lung cancer (NSCLC) patients treated with first-line gefitinib may raise awareness of benefit from anti-HCV treatment in this patient population. Brain metastasis in the initial diagnosis or intracranial progression during gefitinib treatment is not a prognostic factor for OS. This study, which enrolled a real-world population of NSCLC patients, including sicker patients who were not eligible for a clinical trial, may have impact on guiding usual clinical practice. © AlphaMed Press 2017.
Wallentin, Lars; Hijazi, Ziad; Andersson, Ulrika; Alexander, John H; De Caterina, Raffaele; Hanna, Michael; Horowitz, John D; Hylek, Elaine M; Lopes, Renato D; Asberg, Signild; Granger, Christopher B; Siegbahn, Agneta
2014-11-18
Growth differentiation factor 15 (GDF-15), high-sensitivity troponin, and N-terminal pro-brain natriuretic peptide levels are predictive of death and cardiovascular events in healthy elderly subjects, patients with acute coronary syndrome, and patients with heart failure. High-sensitivity troponin I and N-terminal pro-brain natriuretic peptide are also prognostic in patients with atrial fibrillation. We evaluated the prognostic value of GDF-15 alone and in addition to clinical characteristics and other biomarkers in patients with atrial fibrillation. The Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial randomized 18 201 patients with atrial fibrillation to apixaban or warfarin. Biomarkers were measured at randomization in 14 798 patients. Efficacy and safety outcomes during 1.9 years of follow-up were compared across quartiles of GDF-15 by use of Cox analyses adjusted for clinical characteristics, randomized treatment, and other biomarkers. The GDF-15 level showed a median of 1383 ng/L (interquartile range, 977-2052 ng/L). Annual rates of stroke or systemic embolism ranged from 0.9% to 2.03% (P<0.001); of major bleeding, from 1.22% to 4.53% (P<0.001); and of mortality, from 1.34% to 7.19% (P<0.001) in the lowest compared with the highest GDF-15 quartile. The prognostic information provided by GDF-15 was independent of clinical characteristics and clinical risk scores. Adjustment for the other cardiac biomarkers attenuated the prognostic value for stroke, whereas the prognostic value for mortality and major bleeding remained. Apixaban consistently reduced stroke, mortality, and bleeding, regardless of GDF-15 levels. GDF-15 is a risk factor for major bleeding, mortality, and stroke in atrial fibrillation. The prognostic value for major bleeding and death remained even in the presence of N-terminal pro-brain natriuretic peptide and high-sensitivity troponin I. http://www.clinicaltrials.gov. Unique identifier: NCT00412984. © 2014 American Heart Association, Inc.
2006-04-01
for Specific Aim #3 have yet been initiated, and are proceeding on schedule. The PhD candidate has completed her educational goals. 13 Appendix A ... LEVELS OF TELOMERE PROTEIN MRNAS ARE PREDICTIVE OF TELOMERE CONTENT IN HUMAN BREAST TUMORS Kimberly S. Butler, William C. Hines, Diana Roberts
Prognostic Significance of Spouse We Talk in Couples Coping with Heart Failure
ERIC Educational Resources Information Center
Rohrbaugh, Michael J.; Mehl, Matthias R.; Shoham, Varda; Reilly, Elizabeth S.; Ewy, Gordon A.
2008-01-01
Recent research suggests that marital quality predicts the survival of patients with heart failure (HF), and it is hypothesized that a communal orientation to coping marked by first-person plural pronoun use (we talk) may be a factor in this. During a home interview, 57 HF patients (46 men and 16 women) and their spouses discussed how they coped…
SEOM clinical guidelines in early-stage breast cancer 2015.
Garcia-Saenz, J A; Bermejo, B; Estevez, L G; Palomo, A G; Gonzalez-Farre, X; Margeli, M; Pernas, S; Servitja, S; Rodriguez, C A; Ciruelos, E
2015-12-01
Breast cancer is a major public health problem. Despite remarkable advances in early diagnosis and treatment, one in three women may have metastases since diagnosis. Better understanding of prognostic and predictive factors allows us to select the most appropriate adjuvant therapy in each patient. In these guidelines, we summarize current evidence for the medical management of early-stage breast cancer.
Day, C L; Lew, R A; Mihm, M C; Sober, A J; Harris, M N; Kopf, A W; Fitzpatrick, T B; Harrist, T J; Golomb, F M; Postel, A; Hennessey, P; Gumport, S L; Raker, J W; Malt, R A; Cosimi, A B; Wood, W C; Roses, D F; Gorstein, F; Rigel, D; Friedman, R J; Mintzis, M M; Grier, R W
1982-01-01
Fourteen prognostic factors were examined in 79 patients with clinical Stage I melanoma greater than or equal to 3.65 mm in thickness. All nine patients with melanoma of the hands or feet died of melanoma. A Cox proportional hazards (multivariate) analysis of the remaining 70 patients showed that a combination of the following four variables best predicted bony or visceral metastases: 1) a nearly absent or minimal lymphocyte response at the base of the tumor, 2) histologic type other than superficial spreading melanoma, 3) location on the trunk, and 4) positive nodes or no initial node dissection. Ulceration and/or ulceration width were not useful in predicting outcome either singly or in combination with other variables. Patients with negative lymph nodes and primary tumors of the trunk, hands, and feet did not do better than patients with positive nodes at those sites. Conversely, non of 16 patients with negative lymph nodes and extremity melanomas (excluding the hands and feet) or head and neck melanomas developed visceral or bony metastases (i.e., five-year disease-free survival rate 100%). PMID:7055383
Soluble CD30 as a prognostic factor for outcome following renal transplantation.
Platt, R E; Wu, K S T; Poole, K; Newstead, C G; Clark, B
2009-07-01
To determine whether measurement of soluble CD30 (sCD30) levels predicts for early rejection in a cohort of first deceased kidney transplant recipients. Pre-transplant serum samples were analysed for sCD30 levels using a commercial ELISA kit (Biotest). A 100 U/ml cut-off for "high sCD30" was applied. Clinical outcome parameters were biopsy-proven rejection episodes, creatinine levels and glomerular filtration rate. In the cohort of patients who experienced at least one episode of rejection in the first 6 months post-transplant, levels of pre-transplant sCD30 were significantly higher than in those who did not experience rejection. Despite this association, the occurrence of a high sCD30 level did not predict for rejection on an individual basis. The prognostic value of pre-transplant sCD30 testing is diminished by the large number of patients with high sCD30 levels who do not develop rejection. Although this limits the utility of the test in informing clinical management of individual patients, a high pre-transplant sCD30 level should still be considered a risk factor for poorer outcome.
Zhou, Amy; Afzal, Amber; Oh, Stephen T
2017-10-01
The prognosis for patients with Philadelphia chromosome (Ph)-negative myeloproliferative neoplasms (MPNs) is highly variable. All Ph-negative MPNs carry an increased risk for thrombotic complications, bleeding, and leukemic transformation. Several clinical, biological, and molecular prognostic factors have been identified in recent years, which provide important information in guiding management of patients with Ph-negative MPNs. In this review, we critically evaluate the recent published literature and discuss important new developments in clinical and molecular factors that impact survival, disease transformation, and thrombosis in patients with polycythemia vera, essential thrombocythemia, and primary myelofibrosis. Recent studies have identified several clinical factors and non-driver mutations to have prognostic impact on Ph-negative MPNs independent of conventional risk stratification and prognostic models. In polycythemia vera (PV), leukocytosis, abnormal karyotype, phlebotomy requirement on hydroxyurea, increased bone marrow fibrosis, and mutations in ASXL1, SRSF2, and IDH2 were identified as additional adverse prognostic factors. In essential thrombocythemia (ET), JAK2 V617F mutation, splenomegaly, and mutations in SH2B3, SF3B1, U2AF1, TP53, IDH2, and EZH2 were found to be additional negative prognostic factors. Bone marrow fibrosis and mutations in ASXL1, SRSF2, EZH2, and IDH1/2 have been found to be additional prognostic factors in primary myelofibrosis (PMF). CALR mutations appear to be a favorable prognostic factor in PMF, which has not been clearly demonstrated in ET. The prognosis for patients with PV, ET, and PMF is dependent upon the presence or absence of several clinical, biological, and molecular risk factors. The significance of additional risk factors identified in these recent studies will need further validation in prospective studies to determine how they may be best utilized in the management of these disorders.
Kuntegowdanahalli, Lakshmaiah Chinnagiriyappa; Kanakasetty, Govind Babu; Thanky, Aditi Harsh; Dasappa, Lokanatha; Jacob, Linu Abraham; Mallekavu, Suresh Babu; Lakkavalli, Rajeev Krishnappa; Kadabur, Lokesh N; Haleshappa, Rudresha Antapura
2016-01-01
Chronic myeloid leukaemia (CML) is a myeloproliferative disorder. Over the years many prognostic models have been developed to better risk stratify this disease at baseline. Sokal, Euro, and EUTOS scores were developed in varied populations initially receiving various therapies. Here we try to identify their predictive and prognostic implication in a larger population of Indian patients with CML-CP (chronic phase) in the imatinib era.
Predicting functional recovery after acute ankle sprain.
O'Connor, Sean R; Bleakley, Chris M; Tully, Mark A; McDonough, Suzanne M
2013-01-01
Ankle sprains are among the most common acute musculoskeletal conditions presenting to primary care. Their clinical course is variable but there are limited recommendations on prognostic factors. Our primary aim was to identify clinical predictors of short and medium term functional recovery after ankle sprain. A secondary analysis of data from adult participants (N = 85) with an acute ankle sprain, enrolled in a randomized controlled trial was undertaken. The predictive value of variables (age, BMI, gender, injury mechanism, previous injury, weight-bearing status, medial joint line pain, pain during weight-bearing dorsiflexion and lateral hop test) recorded at baseline and at 4 weeks post injury were investigated for their prognostic ability. Recovery was determined from measures of subjective ankle function at short (4 weeks) and medium term (4 months) follow ups. Multivariate stepwise linear regression analyses were undertaken to evaluate the association between the aforementioned variables and functional recovery. Greater age, greater injury grade and weight-bearing status at baseline were associated with lower function at 4 weeks post injury (p<0.01; adjusted R square=0.34). Greater age, weight-bearing status at baseline and non-inversion injury mechanisms were associated with lower function at 4 months (p<0.01; adjusted R square=0.20). Pain on medial palpation and pain on dorsiflexion at 4 weeks were the most valuable prognostic indicators of function at 4 months (p< 0.01; adjusted R square=0.49). The results of the present study provide further evidence that ankle sprains have a variable clinical course. Age, injury grade, mechanism and weight-bearing status at baseline provide some prognostic information for short and medium term recovery. Clinical assessment variables at 4 weeks were the strongest predictors of recovery, explaining 50% of the variance in ankle function at 4 months. Further prospective research is required to highlight the factors that best inform the expected convalescent period, and risk of recurrence.
2014-01-01
Background Prognostic indicators for gastrointestinal stromal tumors (GISTs) are under investigation. The latest risk classification criteria may still have room for improvement. This study aims to investigate prognostic factors for primary GISTs from three aspects, including clinicopathological parameters, immunohistochemical (IHC) expression of PTEN, and Ki-67 labeling index (LI), and attempts to find valuable predictors for the malignancy potential of primary GISTs. Methods Tumor samples and clinicopathological data from 84 patients with primary GISTs after R0 resection were obtained. Immunohistochemical analysis was performed based on tissue microarray (TMA) to estimate expression of PTEN and Ki-67 in tumor cells. Results The cut-off point of Ki-67 LI was determined as 1%, using a receiver operator characteristic test with a sensitivity of 71.7% and a specificity of 64.5%. Univariate analysis demonstrated the following factors as poor prognostic indicators for relapse-free survival (RFS) against a median follow-up of 40.25 months: gastrointestinal (GI) bleeding (P = 0.009), non-gastric tumor location (P = 0.001), large tumor size (P = 0.022), high mitotic index (P < 0.001), high cellularity (P = 0.012), tumor rupture (P = 0.013), absent or low expression of PTEN (P = 0.036), and Ki-67 LI >1% (P = 0.043). Gastrointestinal bleeding (hazard ratio, 3.85; 95% confidence interval, 1.63 to 9.10; P = 0.002) was a negative independent risk predictor in multivariate analysis, in addition to tumor size (P = 0.023), and mitotic index (P = 0.002). In addition, GI bleeding showed a good ability to predict recurrence potential, when included in our re-modified risk stratification criteria. Conclusions This study suggests that GI bleeding is an independent predictor of poor prognosis for RFS in primary GISTs. Expression of PTEN and Ki-67 are correlated with high risk potential and may predict early recurrence in univariate analysis. PMID:24712384
Myasthenic crisis patients who require intensive care unit management.
Sakaguchi, Hideya; Yamashita, Satoshi; Hirano, Teruyuki; Nakajima, Makoto; Kimura, En; Maeda, Yasushi; Uchino, Makoto
2012-09-01
The purpose of this report was to investigate predictive factors that necessitate intensive care in myasthenic crisis (MC). We retrospectively reviewed MC patients at our institution and compared ICU and ward management groups. Higher MG-ADL scale scores, non-ocular initial symptoms, infection-triggered findings, and higher MGFA classification were observed more frequently in the ICU group. In patients with these prognostic factors, better outcomes may be obtained with early institution of intensive care. Copyright © 2012 Wiley Periodicals, Inc.
Lee, Jeunghun; Shishido-Hara, Yukiko; Suzuki, Kaori; Shimizu, Saki; Kobayashi, Keiichi; Kamma, Hiroshi; Shiokawa, Yoshiaki; Nagane, Motoo
2017-10-01
Primary central nervous system lymphoma (PCNSL) remains an aggressive and refractory tumor despite high-dose methotrexate-based chemo-radiotherapy. Age and performance status have been shown to be important clinical prognostic factors, however others, especially molecular factors, affecting the prognosis are still uncertain. We investigate clinical, neuroimaging and immunohistochemical data in tissue from 41 PCNSL patients treated primarily with methotrexate-based chemo-radiotherapy and evaluate the influence of potential prognostic factors on clinical outcome as well as correlation among these factors. Median progression-free survival (PFS) and overall survival (OS) were 29 and 73 months, respectively. Expression of the mismatch repair (MMR) proteins, MLH1, MSH2, MSH6 and PMS2, correlated tightly with each other and high expression of MSH2 was significantly associated with better OS and PFS (P = 0.005 and P = 0.007), while methotrexate metabolism-related proteins did not affect survival. In addition, low expression of PMS2 was an independent predictor of methotrexate resistance (P = 0.039). Among neuroimaging findings, involvement of the fornix and tegmentum/velum were significantly associated with poorer OS (P < 0.001 and P = 0.013) and PFS (P = 0.014 and P = 0.043, respectively). Germinal center B cell (GCB)-PCNSL subtype as opposed to non-GCB subtype, tended toward better survival. Regarding oncogenes, cMYC-positive cases showed unfavorable OS (P = 0.046). By multivariate analysis, MSH2 and involvement of the fornix were independent predictors for both OS and PFS, whereas tegmentum/velum location and cMYC expression were significantly associated with OS. Although further studies are needed, these results suggest that MMR protein expression, as well as specific deep locations and cMYC expression, may be a novel prognostic and predictive markers for PCNSL. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com
Evaluating surrogate endpoints, prognostic markers, and predictive markers — some simple themes
Baker, Stuart G.; Kramer, Barnett S.
2014-01-01
Background A surrogate endpoint is an endpoint observed earlier than the true endpoint (a health outcome) that is used to draw conclusions about the effect of treatment on the unobserved true endpoint. A prognostic marker is a marker for predicting the risk of an event given a control treatment; it informs treatment decisions when there is information on anticipated benefits and harms of a new treatment applied to persons at high risk. A predictive marker is a marker for predicting the effect of treatment on outcome in a subgroup of patients or study participants; it provides more rigorous information for treatment selection than a prognostic marker when it is based on estimated treatment effects in a randomized trial. Methods We organized our discussion around a different theme for each topic. Results “Fundamentally an extrapolation” refers to the non-statistical considerations and assumptions needed when using surrogate endpoints to evaluate a new treatment. “Decision analysis to the rescue” refers to use the use of decision analysis to evaluate an additional prognostic marker because it is not possible to choose between purely statistical measures of marker performance. “The appeal of simplicity” refers to a straightforward and efficient use of a single randomized trial to evaluate overall treatment effect and treatment effect within subgroups using predictive markers. Conclusion The simple themes provide a general guideline for evaluation of surrogate endpoints, prognostic markers, and predictive markers. PMID:25385934
A Testbed for Data Fusion for Helicopter Diagnostics and Prognostics
2003-03-01
and algorithm design and tuning in order to develop advanced diagnostic and prognostic techniques for air craft health monitoring . Here a...and development of models for diagnostics, prognostics , and anomaly detection . Figure 5 VMEP Server Browser Interface 7 Download... detections , and prognostic prediction time horizons. The VMEP system and in particular the web component are ideal for performing data collection
2017-01-01
Several talent development programs in youth soccer have implemented motor diagnostics measuring performance factors. However, the predictive value of such tests for adult success is a controversial topic in talent research. This prospective cohort study evaluated the long-term predictive value of 1) motor tests and 2) players’ speed abilities (SA) and technical skills (TS) in early adolescence. The sample consisted of 14,178 U12 players from the German talent development program. Five tests (sprint, agility, dribbling, ball control, shooting) were conducted and players’ height, weight as well as relative age were assessed at nationwide diagnostics between 2004 and 2006. In the 2014/15 season, the players were then categorized as professional (n = 89), semi-professional (n = 913), or non-professional players (n = 13,176), indicating their adult performance level (APL). The motor tests’ prognostic relevance was determined using ANOVAs. Players’ future success was predicted by a logistic regression threshold model. This structural equation model comprised a measurement model with the motor tests and two correlated latent factors, SA and TS, with simultaneous consideration for the manifest covariates height, weight and relative age. Each motor predictor and anthropometric characteristic discriminated significantly between the APL (p < .001; η2 ≤ .02). The threshold model significantly predicted the APL (R2 = 24.8%), and in early adolescence the factor TS (p < .001) seems to have a stronger effect on adult performance than SA (p < .05). Both approaches (ANOVA, SEM) verified the diagnostics’ predictive validity over a long-term period (≈ 9 years). However, because of the limited effect sizes, the motor tests’ prognostic relevance remains ambiguous. A challenge for future research lies in the integration of different (e.g., person-oriented or multilevel) multivariate approaches that expand beyond the “traditional” topic of single tests’ predictive validity and toward more theoretically founded issues. PMID:28806410
Lanic, Hélène; Kraut-Tauzia, Jerôme; Modzelewski, Romain; Clatot, Florian; Mareschal, Sylvain; Picquenot, Jean Michel; Stamatoullas, Aspasia; Leprêtre, Stéphane; Tilly, Hervé; Jardin, Fabrice
2014-04-01
Approximately 25-35% of patients with diffuse large B-cell lymphoma (DLBCL) are older than 70 years. The aim of this study was to investigate the prognostic impact of depletion of skeletal muscle (sarcopenia) in elderly patients with DLBCL. This retrospective analysis included 82 patients with DLBCL older than 70 years and treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, Oncovin, prednisone) or R-miniCHOP. Sarcopenia was measured by the analysis of stored computed tomography (CT) images at the L3 level at baseline. The surface of the muscular tissues was selected according to the CT Hounsfield unit. This value was normalized for stature in order to calculate the lumbar L3 skeletal muscle index (LSMI, in cm(2)/m(2)). The mean age of the population was 78 years. According to the defined cut-offs for LSMI, 45 patients with DLBCL were considered sarcopenic. Sarcopenic patients displayed a higher revised International Prognostic Index (R-IPI) compared with patients without sarcopenia, and were older, with a mean age of 80 years and 77 years, respectively (p = 0.006). With a median follow-up of 39 months, the 2-year overall survival in the sarcopenic population was 46% compared with 84% in the non-sarcopenic group (HR = 3.22; 95% CI = 1.73-5.98; p = 0.0002). In a multivariate analysis, sarcopenia remained predictive of outcome (p = 0.005). Sarcopenia is a relevant and predictive factor in elderly patients with DLBCL treated with rituximab plus chemotherapy.
Frazer, J; Couban, S; Doucette, S; Shivakumar, S
2017-04-01
Allogeneic hematopoietic stem-cell transplantation (ahsct) is associated with significant morbidity and mortality, but it can cure carefully selected patients with acute myeloid leukemia (aml) in second remission (cr2). In a cohort of patients with aml who underwent ahsct in cr2, we determined the pre-transplant factors that predicted for overall survival (os), relapse, and non-relapse mortality. We also sought to validate the prognostic risk groups derived by Michelis and colleagues in this independent population. In a retrospective chart review, we obtained data for 55 consecutive patients who underwent ahsct for aml in cr2. Hazard ratios were used to describe the independent effects of pre-transplant variables on outcome, and Kaplan-Meier curves were used to assess outcomes in the three prognostic groups identified by Michelis and colleagues. At 1, 3, and 5 years post-transplant, os was 60%, 45.5%, and 37.5% respectively. Statistically significant differences in os, relapse mortality, and non-relapse mortality were not identified between the prognostic risk groups identified by Michelis and colleagues. Women were less likely than men to relapse, and a modified European Society for Blood and Marrow Transplantation (mebmt) score of 3 or less was associated with a lower non-relapse mortality. The 37.5% 5-year os in this cohort suggests that, compared with other options, ahsct offers patients with aml in cr2 a better chance of cure. Our study supports the use of the mebmt score to predict non-relapse mortality in this population.
Yun, Dapeng; Zhao, Yingjie; Wang, Jingkun; Xu, Tao; Li, Xiaoying; Wang, Yuqi; Yuan, Li; Sun, Ruochuan; Song, Xiao; Huai, Cong; Hu, Lingna; Yang, Song; Min, Taishan; Chen, Juxiang; Chen, Hongyan; Lu, Daru
2015-01-01
Glioma is the most malignant brain tumor and glioblastoma (GBM) is the most aggressive type. The involvement of N-myc (and STAT) interactor (NMI) in tumorigenesis was sporadically reported but far from elucidation. This study aims to investigate roles of NMI in human glioma. Three independent cohorts, the Chinese tissue microarray (TMA) cohort (N = 209), the Repository for Molecular Brain Neoplasia Data (Rembrandt) cohort (N = 371) and The Cancer Genome Atlas (TCGA) cohort (N = 528 or 396) were employed. Transcriptional or protein levels of NMI expression were significantly increased according to tumor grade in all three cohorts. High expression of NMI predicted significantly unfavorable clinical outcome for GBM patients, which was further determined as an independent prognostic factor. Additionally, expression and prognostic value of NMI were associated with molecular features of GBM including PTEN deletion and EGFR amplification in TCGA cohort. Furthermore, overexpression or depletion of NMI revealed its regulation on G1/S progression and cell proliferation (both in vitro and in vivo), and this effect was partially dependent on STAT1, which interacted with and was regulated by NMI. These data demonstrate that NMI may serve as a novel prognostic biomarker and a potential therapeutic target for glioblastoma. PMID:25669971
Kobayashi, Takashi; Teruya, Masanori; Kishiki, Tomokazu; Endo, Daisuke; Takenaka, Yoshiharu; Miki, Kenji; Kobayashi, Kaoru; Morita, Koji
2010-01-01
Few studies have investigated whether the Glasgow Prognostic Score (GPS), an inflammation-based prognostic score measured before resection of colorectal liver metastasis (CRLM), can predict postoperative survival. Sixty-three consecutive patients who underwent curative resection for CRLM were investigated. GPS was calculated on the basis of admission data as follows: patients with both an elevated C-reactive protein (>10 mg/l) and hypoalbuminemia (<35 g/l) were allocated a GPS score of 2. Patients in whom only one of these biochemical abnormalities was present were allocated a GPS score of 1, and patients with a normal C-reactive protein and albumin were allocated a score of 0. Significant factors concerning survival were the number of liver metastases (p = 0.0044), carcinoembryonic antigen level (p = 0.0191), GPS (p = 0.0029), grade of liver metastasis (p = 0.0033), and the number of lymph node metastases around the primary cancer (p = 0.0087). Multivariate analysis showed the two independent prognostic variables: liver metastases > or =3 (relative risk 2.83) and GPS1/2 (relative risk 3.07). GPS measured before operation and the number of liver metastases may be used as novel predictors of postoperative outcomes in patients who underwent curative resection for CRLM. Copyright 2010 S. Karger AG, Basel.
Meng, Delong; Chen, Yuanyuan; Yun, Dapeng; Zhao, Yingjie; Wang, Jingkun; Xu, Tao; Li, Xiaoying; Wang, Yuqi; Yuan, Li; Sun, Ruochuan; Song, Xiao; Huai, Cong; Hu, Lingna; Yang, Song; Min, Taishan; Chen, Juxiang; Chen, Hongyan; Lu, Daru
2015-03-10
Glioma is the most malignant brain tumor and glioblastoma (GBM) is the most aggressive type. The involvement of N-myc (and STAT) interactor (NMI) in tumorigenesis was sporadically reported but far from elucidation. This study aims to investigate roles of NMI in human glioma. Three independent cohorts, the Chinese tissue microarray (TMA) cohort (N = 209), the Repository for Molecular Brain Neoplasia Data (Rembrandt) cohort (N = 371) and The Cancer Genome Atlas (TCGA) cohort (N = 528 or 396) were employed. Transcriptional or protein levels of NMI expression were significantly increased according to tumor grade in all three cohorts. High expression of NMI predicted significantly unfavorable clinical outcome for GBM patients, which was further determined as an independent prognostic factor. Additionally, expression and prognostic value of NMI were associated with molecular features of GBM including PTEN deletion and EGFR amplification in TCGA cohort. Furthermore, overexpression or depletion of NMI revealed its regulation on G1/S progression and cell proliferation (both in vitro and in vivo), and this effect was partially dependent on STAT1, which interacted with and was regulated by NMI. These data demonstrate that NMI may serve as a novel prognostic biomarker and a potential therapeutic target for glioblastoma.
A CpG-methylation-based assay to predict survival in clear cell renal cell carcinoma
Wei, Jin-Huan; Haddad, Ahmed; Wu, Kai-Jie; Zhao, Hong-Wei; Kapur, Payal; Zhang, Zhi-Ling; Zhao, Liang-Yun; Chen, Zhen-Hua; Zhou, Yun-Yun; Zhou, Jian-Cheng; Wang, Bin; Yu, Yan-Hong; Cai, Mu-Yan; Xie, Dan; Liao, Bing; Li, Cai-Xia; Li, Pei-Xing; Wang, Zong-Ren; Zhou, Fang-Jian; Shi, Lei; Liu, Qing-Zuo; Gao, Zhen-Li; He, Da-Lin; Chen, Wei; Hsieh, Jer-Tsong; Li, Quan-Zhen; Margulis, Vitaly; Luo, Jun-Hang
2015-01-01
Clear cell renal cell carcinomas (ccRCCs) display divergent clinical behaviours. Molecular markers might improve risk stratification of ccRCC. Here we use, based on genome-wide CpG methylation profiling, a LASSO model to develop a five-CpG-based assay for ccRCC prognosis that can be used with formalin-fixed paraffin-embedded specimens. The five-CpG-based classifier was validated in three independent sets from China, United States and the Cancer Genome Atlas data set. The classifier predicts the overall survival of ccRCC patients (hazard ratio=2.96−4.82; P=3.9 × 10−6−2.2 × 10−9), independent of standard clinical prognostic factors. The five-CpG-based classifier successfully categorizes patients into high-risk and low-risk groups, with significant differences of clinical outcome in respective clinical stages and individual ‘stage, size, grade and necrosis' scores. Moreover, methylation at the five CpGs correlates with expression of five genes: PITX1, FOXE3, TWF2, EHBP1L1 and RIN1. Our five-CpG-based classifier is a practical and reliable prognostic tool for ccRCC that can add prognostic value to the staging system. PMID:26515236
Risk and prognostic factors of ventilator-associated pneumonia in trauma patients.
Cavalcanti, Manuela; Ferrer, Miquel; Ferrer, Ricard; Morforte, Ramon; Garnacho, Angel; Torres, Antoni
2006-04-01
To assess the risk and prognostic factors of ventilator-associated pneumonia in trauma patients, with an emphasis on the inflammatory response. Case-control study. Trauma intensive care unit. Of 190 consecutive mechanically ventilated patients, those with microbiologically confirmed pneumonia (n = 62) were matched with 62 controls without pneumonia. None. Clinical, microbiological, and outcome variables were recorded. Cytokines were measured in serum and blind bronchoalveolar lavage specimens at onset of pneumonia. Multivariate analyses of risk and prognostic factors for ventilator-associated pneumonia were done. Increased severity of head and neck injury (odds ratio, 11.9; p < .001) was the only independent predictor of pneumonia. Among patients with pneumonia, serum levels of interleukin-6 (p = .019) and interleukin-8 (p = .036) at onset of pneumonia were higher in nonresponders to treatment. Moreover, serum levels of tumor necrosis factor-alpha (p = .028) and interleukin-6 (p = .007) at onset of pneumonia were higher in nonsurvivors. Mortality in the intensive care unit was 23% in cases and controls. Nonresponse to antimicrobial treatment (odds ratio, 22.2; p = .001) and the use of hyperventilation (p = .021) were independent predictors of mortality in the intensive care unit for patients with pneumonia. Severe head and neck trauma is strongly associated with ventilator-associated pneumonia. A higher inflammatory response is associated with nonresponse to treatment and mortality among patients with pneumonia. Although pneumonia did not influence mortality, nonresponse to treatment independently predicted mortality among these patients.
A Nomogram to Predict Anastomotic Leakage in Open Rectal Surgery-Hope or Hype?
Klose, Johannes; Tarantino, Ignazio; von Fournier, Armin; Stowitzki, Moritz J; Kulu, Yakup; Bruckner, Thomas; Volz, Claudia; Schmidt, Thomas; Schneider, Martin; Büchler, Markus W; Ulrich, Alexis
2018-05-18
Anastomotic leakage is the most dreaded complication after rectal resection and total mesorectal excision, leading to increased morbidity and mortality. Formation of a diverting ileostomy is generally performed to protect anastomotic healing. Identification of variables predicting anastomotic leakage might help to select patients who are under increased risk for the development of anastomotic leakage prior to surgery. The objective of this study was to assess the applicability of a nomogram as prognostic model for the occurrence of anastomotic leakage after rectal resection in a cohort of rectal cancer patients. Nine hundred seventy-two consecutive patients who underwent surgery for rectal cancer were retrospectively analyzed. Univariate and multivariable Cox regression analyses were used to determine independent risk factors associated with anastomotic leakage. Receiver operating characteristics (ROC) curve analysis was performed to calculate the sensitivity, specificity, and overall model correctness of a recently published nomogram and an adopted risk score based on the variables identified in this study as a predictive model. Male sex (p = 0.042), obesity (p = 0.017), smoking (p = 0.012), postoperative bleeding (p = 0.024), and total protein level ≤ 5.6 g/dl (p = 0.007) were identified as independent risk factors for anastomotic leakage. The investigated nomogram and the adopted risk score failed to reach relevant areas under the ROC curve greater than 0.700 for the prediction of anastomotic leakage. The proposed nomogram and the adopted risk score failed to reliably predict the occurrence of anastomotic leakage after rectal resection. Risk scores as prognostic models for the prediction of anastomotic leakage, independently of the study population, still need to be identified.
Prognostic value of long noncoding RNA HOTAIR in digestive system malignancies.
Wang, Shuai; Wang, Zhou
2015-07-01
HOX transcript antisense intergenic RNA (HOTAIR), a well-known long noncoding RNA, has been found to play significant roles in several tumors. However, the clinical application value of HOTAIR in digestive system malignancies remains to be clarified. We aimed to explore comprehensively the potential role of HOTAIR as a prognostic indicator in digestive system malignancies. Systematic search was performed in Pubmed, Embase, Cochrane Library, and Web of Science until July 5, 2014. A quantitative meta-analysis was conducted with standard statistical methods for eligible papers on the prognostic value of HOTAIR in digestive system cancers. A total of 1059 patients from 13 studies were included in the meta-analysis. A significant association was found between HOTAIR abundance and poor overall survival (OS) of patients with digestive system malignancies, with pooled hazard ratio (HR) of 2.587 (95% confidence interval [CI]: 2.054-3.259, P < 0.001). By combining HRs from Cox multivariate analyses, we found HOTAIR was an independent prognostic factor for OS without obvious heterogeneity (HR: 2.405, 95% CI: 1.883-3.0722, P < 0.001). Subgroup analysis showed that tumor type, histology type, region, publication year, sample size, and quality score did not alter the predictive value of HOTAIR as an independent factor for survival. Meta-regression and sensitivity analysis both suggested the reliability of our findings. A slight publication bias was observed. After adjustment by nonparametric "trim-and-fill" method, the corrected HRs had no significant change. HOTAIR could be exploited as a novel prognostic biomarker for patients with digestive system malignancies. © 2015 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.
Wang, Chenghu; Zhou, Yi; Chen, Beibei; Yuan, Weiwei; Huang, Jinxi
2018-04-01
Tripartite motif containing 29 (TRIM29) dysregulation serves an important function in the progression of numerous types of cancer, but its function in the prognosis of patients with gastric cancer remains unknown. The present study assessed the prognostic value of TRIM29 in patients with gastric cancer following surgical resection. A total of 243 fresh gastric adenocarcinoma and adjacent normal tissues were continuously retrieved from patients who underwent curative surgery for gastric cancer at the Cancer Hospital of Henan Province (Zhengzhou, China) between January 2005 and December 2011. The reverse transcription-quantitative polymerase chain reaction was performed to assess TRIM29 expression. The association between TRIM29 expression and clinicopathological features and prognosis was subsequently evaluated. The results of the present study revealed that the expression of TRIM29 was increased in the gastric cancer tissues compared with the normal adjacent tissues, and that upregulated expression of TRIM29 was associated with tumor cell differentiation, tumor stage, lymph node metastasis, and tumor-node-metastasis (TNM) stage. In the training and validation data, high TRIM29 expression was associated with poor overall survival in patients with gastric cancer. Furthermore, multivariate analysis identified that TRIM29 expression was an independent prognostic factor for overall survival, in addition to TNM stage and Lauren classification. Combining TRIM29 expression with the TNM staging system generated a novel predictive model that exhibited improved prognostic accuracy for overall survival in patients with gastric cancer. The present study revealed that TRIM29 was an independent adverse prognostic factor in patients with gastric cancer. Incorporating TRIM29 expression level into the TNM staging system may improve risk stratification and render prognosis more accurate in patients with gastric cancer.
Thai venous stroke prognostic score: TV-SPSS.
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.
Takada, Kazuki; Toyokawa, Gouji; Shoji, Fumihiro; Okamoto, Tatsuro; Maehara, Yoshihiko
2018-03-01
Lung cancer is the leading cause of death due to cancer worldwide. Surgery, chemotherapy, and radiotherapy have been the standard treatment for lung cancer, and targeted molecular therapy has greatly improved the clinical course of patients with non-small-cell lung cancer (NSCLC) harboring driver mutations, such as in epidermal growth factor receptor and anaplastic lymphoma kinase genes. Despite advances in such therapies, the prognosis of patients with NSCLC without driver oncogene mutations remains poor. Immunotherapy targeting programmed cell death-1 (PD-1) and programmed cell death-ligand 1 (PD-L1) has recently been shown to improve the survival in advanced NSCLC. The PD-L1 expression on the surface of tumor cells has emerged as a potential biomarker for predicting responses to immunotherapy and prognosis after surgery in NSCLC. However, the utility of PD-L1 expression as a predictive and prognostic biomarker remains controversial because of the existence of various PD-L1 antibodies, scoring systems, and positivity cutoffs. In this review, we summarize the data from representative clinical trials of PD-1/PD-L1 immune checkpoint inhibitors in NSCLC and previous reports on the association between PD-L1 expression and clinical outcomes in patients with NSCLC. Furthermore, we discuss the future perspectives of immunotherapy and immune checkpoint factors. Copyright © 2017 Elsevier Inc. All rights reserved.
Towards Prognostics of Electrolytic Capacitors
NASA Technical Reports Server (NTRS)
Celaya, Jose R.; Kulkarni, Chetan; Biswas, Gautam; Goegel, Kai
2011-01-01
A remaining useful life prediction algorithm and degradation model for electrolytic capacitors is presented. Electrolytic capacitors are used in several applications ranging from power supplies on critical avionics equipment to power drivers for electro-mechanical actuators. These devices are known for their low reliability and given their criticality in electronics subsystems they are a good candidate for component level prognostics and health management research. Prognostics provides a way to assess remaining useful life of a capacitor based on its current state of health and its anticipated future usage and operational conditions. In particular, experimental results of an accelerated aging test under electrical stresses are presented. The capacitors used in this test form the basis for a remaining life prediction algorithm where a model of the degradation process is suggested. This preliminary remaining life prediction algorithm serves as a demonstration of how prognostics methodologies could be used for electrolytic capacitors.
SALAH, SAMER; TOUBASI, SAMAR
2015-01-01
Pulmonary metastasectomy (PM) is associated with improved survival of patients with metastatic osteosarcoma; however, the factors affecting survival following achievement of complete surgical remission remain controversial. The main objective of this study was to report the outcomes and prognostic factors of osteosarcoma patients who achieved complete remission (CR) following PM. We analyzed the effect of demographic and disease-related characteristics on the overall survival (OS) of consecutive patients with metastatic osteosarcoma who were treated at a single institution and achieved CR following PM, through univariate and multivariate analyses. Between January, 2000 and August, 2013, 62 patients with metastatic osteosarcoma were treated and followed up at our institution. A total of 25 patients achieved CR following PM and were included in this analysis. The 5-year OS and disease-free survival following PM were 30 and 21%, respectively. The factors correlated with inferior OS in the univariate analysis included chondroblastic subtype, post-chemotherapy necrosis <90% in the primary tumor, metastasis detected during neoadjuvant or adjuvant chemotherapy and pathological identification of tumor cells reaching the visceral pleural surface of any of the resected nodules. In the multivariate analysis, the chondroblastic subtype was the sole independent adverse prognostic factor (HR=4.6, 95% CI: 1.0–21.3, P=0.044). Therefore, factors associated with tumor biology, including poor tumor necrosis in the primary tumor and detection of metastasis during primary chemotherapy, are associated with poor post-metastasectomy survival. In addition, chondroblastic subtype and visceral pleural involvement predicted poor prognosis in our series. PMID:25469287
Abrao, Fernando Conrado; Peixoto, Renata D'Alpino; de Abreu, Igor Renato Louro Bruno; Janini, Maria Cláudia; Viana, Geisa Garcia; de Oliveira, Mariana Campello; Younes, Riad Naim
2016-04-01
The aim of this study was to identify predictors of mortality only in patients with malignant pleural effusion (MPE) showing good performance status which required pleural palliative procedures. All patients with MPE submitted to pleural palliative procedure were enrolled in a prospective study between 2013 and 2014. Patients with Eastern cooperative oncology group (ECOG) score zero, one, and two were considered with good performance status. The possible prognostic factors were tested for significance using the log-rank test (Kaplan-Meier method) and those with significance on univariate analysis were entered into a multivariable Cox model. A total of 64 patients were included in the analysis. Median follow-up time for surviving patients was 263 days. Median survival for the entire cohort was not reached yet. In the multivariate analysis, gastrointestinal primary site (P = 0.006), low albumin concentration in the pleural fluid (P = 0.017), and high serum NLR (P = 0.007) were associated with mortality. In our cohort of ECOG 0-2 patients with MPE submitted to pleural palliative procedures, gastrointestinal malignancy compared to other sites, low pleural fluid albumin and high NLR were significantly associated with mortality. The identification of these prognostic factors may assist the choice of the optimal palliative technique. J. Surg. Oncol. 2016;113:570-574. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.
A prospective study on MRI findings and prognostic factors in athletes with MTSS.
Moen, M H; Schmikli, S L; Weir, A; Steeneken, V; Stapper, G; de Slegte, R; Tol, J L; Backx, F J G
2014-02-01
In medial tibial stress syndrome (MTSS) bone marrow and periosteal edema of the tibia on the magnetic resonance imaging (MRI) is frequently reported. The relationship between these MRI findings and recovery has not been previously studied. This prospective study describes MRI findings of 52 athletes with MTSS. Baseline characteristics were recorded and recovery was related to these parameters and MRI findings to examine for prognostic factors. Results showed that 43.5% of the symptomatic legs showed bone marrow or periosteal edema. Absence of periosteal and bone marrow edema on MRI was associated with longer recovery (P = 0.033 and P = 0.013). A clinical scoring system for sports activity (SARS score) was significantly higher in the presence of bone marrow edema (P = 0.027). When clinical scoring systems (SARS score and the Lower Extremity Functional Scale) were combined in a model, time to recovery could be predicted substantially (explaining 54% of variance, P = 0.006). In conclusion, in athletes with MTSS, bone marrow or periosteal edema is seen on MRI in 43,5% of the symptomatic legs. Furthermore, periosteal and bone marrow edema on MRI and clinical scoring systems are prognostic factors. Future studies should focus on MRI findings in symptomatic MTSS and compare these with a matched control group. © 2012 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Pandith, Arshad A; Qasim, Iqbal; Zahoor, Wani; Shah, Parveen; Bhat, Abdul R; Sanadhya, Dheera; Shah, Zafar A; Naikoo, Niyaz A
2018-04-30
O 6 -methylguanine-DNA methyltransferase (MGMT) promoter methylation and its subsequent loss of protein expression has been identified to have a variable impact on clinical outcome of glioma patients indicated for chemotherapy with alkylating agents (Temozolomide). This study investigated methylation status of MGMT gene along with in situ protein expression in malignant glioma patients of different histological types to evaluate the associated clinical outcome vis-a-vis use of alkylating drugs and radiotherapy. Sixty three cases of glioma were evaluated for MGMT promoter methylation by methylation-specific PCR (MS-PCR) and protein expression by immunostaining (IHC). Methylation status of MGMT and loss of protein expression showed a very high concordant association with better survival and progression free survival (PFS) (p < 0.0001). Multivariate Cox regression analysis showed both MGMT methylation and loss of protein as significant independent prognostic factors in glioma patients with respect to lower Hazard Ratio (HR) for better OS and PFS) [p < 0.05]. Interestingly concordant MGMT methylation and lack of protein showed better response in TMZ therapy treated patient subgroups with HR of 2.02 and 0.76 (p < 0.05). We found the merits of prognostication of MGMT parameters, methylation as well as loss of its protein as predictive factors for favorable outcome in terms of better survival for TMZ therapy.
Prognostic factors in prostate cancer patients treated by radical external beam radiotherapy.
Garibaldi, Elisabetta; Gabriele, Domenico; Maggio, Angelo; Delmastro, Elena; Garibaldi, Monica; Russo, Filippo; Bresciani, Sara; Stasi, Michele; Gabriele, Pietro
2017-09-01
The aim of this paper was to analyze, retrospectively, in prostate cancer patients treated in our Centre with external beam radiotherapy, the prognostic factors and their impact on the outcome in terms of cancer-specific survival (CSS), biochemical disease-free survival (BDFS) and clinical disease-free survival (CDFS). From October 1999 and March 2012, 1080 patients were treated with radiotherapy at our Institution: 87% of them were classified as ≤cT2, 83% had a Gleason Score (GS) ≤7, their mean of iPSA was 18 ng/mL, and the rate of clinical positive nodes was 1%. The mean follow-up was 81 months. The statistically significant prognostic factors for all groups of patients at both, univariate and multivariate analysis, were the GS and the iPSA. In intermediate- and high- or very-high-risk patients at multivariate analysis other prognostic factors for CSS were positive nodes on computed tomography (CT) scan and rectal preparation during the treatment; for BDFS, the prognostic factors were patient risk classification, positive lymph nodes on CT scan and rectal/bladder preparation; for CDFS, the prognostic factors were the number of positive core on biopsy (P=0.003), positive lymph nodes on CT scan, and radiotherapy (RT) dose. In high/very-high risk patient group at multivariate analysis other prognostic factors for CSS were clinical/radiological stage and RT dose, for BDFS they were adjuvant hormone therapy, clinical/radiological stage, and RT dose >77.7 Gy, and for CDFS they were clinical/radiological stage and RT dose >77.7 Gy. The results of this study confirm the prognostic factors described in the recent literature, with the addition of rectal/bladder preparation, generally known for its effect on toxicity but not yet on outcome.
USDA-ARS?s Scientific Manuscript database
Background. Prior studies suggest that elevated markers of bone turnover are prognostic for poor survival in castration resistant prostate cancer (CRPC). The predictive role of these markers relative to bone-targeted therapy is unknown. We prospectively evaluated the prognostic and predictive value ...
Jiang, Ai-Gui; Chen, Hong-Lin; Lu, Hui-Yu
2015-03-01
Previous studies have shown that Glasgow prognostic score (GPS) and prognostic index (PI) are also powerful prognostic tool for patients with advanced non-small cell lung cancer (NSCLC). The aim of this study was to compare the prognostic value between GPS and PI. We enrolled consecutive patients with advanced NSCLC in this prospective cohort. GPS and PI were calculated before the onset of chemotherapy. The prognosis outcomes included 1-, 3-, and 5-year progression-free survival and overall survival (OS). The performance of two scores in predicting prognosis was analyzed regarding discrimination and calibration. 138 patients were included in the study. The area under the receiver operating characteristic curve for GPS predicting 1-year DFS was 0.62 (95 % confidence interval (CI) 0.56-0.68, P < 0.05), and the area under curve for PI predicting 1-year DFS was 0.57 (95 % CI 0.52-0.63). Delong's test showed that GPS was more accurate than PI in predicting 1-year DFS (P < 0.05). Similar results of discriminatory power were found for predicting 3-year DFS, 1-year OS, and 3-year OS. The predicted 1-year DFS by GPS 0, GPS 1, and GPS 2 were 62.5, 42.1, and 23.1 %, respectively, while actual 1-year DFS by GPS 0, GPS 1, and GPS 2 were 61.1, 43.8, and 27.2 %, respectively. Calibration of the Hosmer and Lemeshow statistic showed good fit of the predicted 1-year DFS to the actual 1-year DFS by GPS (χ(2) = 4.326, P = 0.462), while no fit was found between the predicted 1-year DFS and the actual 1-year DFS by PI (χ(2) = 15.234, P = 0.091). Similar results of calibration power were found for predicting 3-year DFS, 5-year DFS, 1-year OS, 3-year OS, and 5-year OS by GPS and PI. GPS is more accurate than PI in predicting prognosis for patients with advanced NSCLC. GPS can be used as a useful and simple tool for predicting prognosis in patients with NSCLC. However, GPS only can be used for preliminary assessment because of low predicting accuracy.
Impact of disseminated tumor cells in gastrointestinal cancer.
Thorban, Stefan; Rosenberg, Robert; Maak, Matthias; Friederichs, Jan; Gertler, Ralf; Siewert, Jörg-Rüdiger
2006-05-01
The detection of epithelial cells by sensitive immunological and molecular methods in blood, lymph nodes or bone marrow of gastrointestinal cancer patients may open a new approach to clinical metastasis research. The phenotypic and genomic characterization of these cells is of great value in the prediction of the further course of the disease and the monitoring of response to treatment. In addition, the role of ultrastaging in blood, lymph nodes and bone marrow of cancer patients for the indication of multimodal therapy is discussed in this review. The impact of prognostic or predictive factors for new treatment protocols in patients with gastrointestinal cancer was evaluated as well as the correlation with clinical factors.
A Model-Based Prognostics Approach Applied to Pneumatic Valves
NASA Technical Reports Server (NTRS)
Daigle, Matthew J.; Goebel, Kai
2011-01-01
Within the area of systems health management, the task of prognostics centers on predicting when components will fail. Model-based prognostics exploits domain knowledge of the system, its components, and how they fail by casting the underlying physical phenomena in a physics-based model that is derived from first principles. Uncertainty cannot be avoided in prediction, therefore, algorithms are employed that help in managing these uncertainties. The particle filtering algorithm has become a popular choice for model-based prognostics due to its wide applicability, ease of implementation, and support for uncertainty management. We develop a general model-based prognostics methodology within a robust probabilistic framework using particle filters. As a case study, we consider a pneumatic valve from the Space Shuttle cryogenic refueling system. We develop a detailed physics-based model of the pneumatic valve, and perform comprehensive simulation experiments to illustrate our prognostics approach and evaluate its effectiveness and robustness. The approach is demonstrated using historical pneumatic valve data from the refueling system.
Park, Sung-Soo; Kim, Hee-Je; Min, Kyoung Il; Min, Gi June; Jeon, Young-Woo; Yoon, Jae-Ho; Yahng, Seung-Ah; Shin, Seung-Hwan; Lee, Sung-Eun; Cho, Byung-Sik; Eom, Ki-Seong; Kim, Yoo-Jin; Lee, Seok; Min, Chang-Ki; Cho, Seok-Goo; Kim, Dong-Wook; Lee, Jong Wook; Min, Woo-Sung
2018-04-01
To identify factors affecting survival outcomes and to develop a prognostic model for second allogeneic stem-cell transplantation (allo-SCT2) for relapsed acute myeloid leukemia (AML) after the first autologous or allogeneic stem-cell transplantation. Seventy-eight consecutive adult AML patients who received allo-SCT2 were analyzed in this retrospective study. The 4-year overall survival (OS) rate was 28.7%. In multivariate analysis, poor cytogenetic risk at diagnosis, circulating blast ≥ 20% at relapse, duration from first transplantation to relapse < 9 months, and failure to achieve morphologic complete remission after allo-SCT2 were factors associated with poor OS. A prognostic model was developed with the following score system: intermediate and poor cytogenetic risk at diagnosis (0.5 and 1 point), peripheral blast ≥ 20% at relapse (1 point), duration from the first transplantation to relapse < 9 months (1 point), and failure to achieve morphologic complete remission after allo-SCT2 (1 point). The model identified 2 subgroups according to the 4-year OS rate: 51.3% in the low-risk group (score < 2) and 2.8% in the high-risk group (score ≥ 2) (P < .001). This prognostic model might be useful to make an appropriate decision for allo-SCT2 in relapsed AML after the first autologous or allogeneic stem-cell transplantation. Copyright © 2018 Elsevier Inc. All rights reserved.
Wang, Gang; Wang, Qian; Li, Zhengyan; Liu, Chaoxu; He, Xianli
2018-01-01
Xenopus kinesin-like protein 2 (TPX2) is a microtubule-associated protein that plays an important role in spindle assembly and dynamics. However, the clinical and prognostic value of TPX2 in the digestive system cancers remains unclear. The objective of this review was to evaluate the association of TPX2 expression with disease-free survival (DFS), overall survival (OS), and clinicopathological features of digestive system cancers. The software Stata 12.0 was used to analyze the outcomes, including OS, disease-free survival (DFS), and clinicopathological characteristics. A total of 10 eligible studies with 906 patients were included. Elevated TPX2 expression was significantly associated with poor DFS (pooled hazard ratio [HR] =2.48, 95% confidence interval [CI]: 1.96-3.13) and OS (pooled HR =2.66, 95% CI: 2.04-3.48) of digestive system malignancies. Subgroup analyses showed that cancer type, sample size, study quality, and laboratory detection methods did not alter the significant prognostic value of TPX2. Additionally, TPX2 expression was found to be an independent predictive factor for DFS (HR =2.31, 95% CI: 1.78-3.01). TPX2 expression might be associated with TNM stage and pathological grade in digestive system cancer. In conclusion, TPX2 is an independent prognostic factor for survival of patients with digestive system cancer. Furthermore, its overexpression is associated with TNM stage and pathological grade in digestive system cancer.
Liu, Chaoxu; He, Xianli
2018-01-01
Xenopus kinesin-like protein 2 (TPX2) is a microtubule-associated protein that plays an important role in spindle assembly and dynamics. However, the clinical and prognostic value of TPX2 in the digestive system cancers remains unclear. The objective of this review was to evaluate the association of TPX2 expression with disease-free survival (DFS), overall survival (OS), and clinicopathological features of digestive system cancers. The software Stata 12.0 was used to analyze the outcomes, including OS, disease-free survival (DFS), and clinicopathological characteristics. A total of 10 eligible studies with 906 patients were included. Elevated TPX2 expression was significantly associated with poor DFS (pooled hazard ratio [HR] =2.48, 95% confidence interval [CI]: 1.96–3.13) and OS (pooled HR =2.66, 95% CI: 2.04–3.48) of digestive system malignancies. Subgroup analyses showed that cancer type, sample size, study quality, and laboratory detection methods did not alter the significant prognostic value of TPX2. Additionally, TPX2 expression was found to be an independent predictive factor for DFS (HR =2.31, 95% CI: 1.78–3.01). TPX2 expression might be associated with TNM stage and pathological grade in digestive system cancer. In conclusion, TPX2 is an independent prognostic factor for survival of patients with digestive system cancer. Furthermore, its overexpression is associated with TNM stage and pathological grade in digestive system cancer. PMID:29551902
NASA Astrophysics Data System (ADS)
Yu, Jianbo
2015-12-01
Prognostics is much efficient to achieve zero-downtime performance, maximum productivity and proactive maintenance of machines. Prognostics intends to assess and predict the time evolution of machine health degradation so that machine failures can be predicted and prevented. A novel prognostics system is developed based on the data-model-fusion scheme using the Bayesian inference-based self-organizing map (SOM) and an integration of logistic regression (LR) and high-order particle filtering (HOPF). In this prognostics system, a baseline SOM is constructed to model the data distribution space of healthy machine under an assumption that predictable fault patterns are not available. Bayesian inference-based probability (BIP) derived from the baseline SOM is developed as a quantification indication of machine health degradation. BIP is capable of offering failure probability for the monitored machine, which has intuitionist explanation related to health degradation state. Based on those historic BIPs, the constructed LR and its modeling noise constitute a high-order Markov process (HOMP) to describe machine health propagation. HOPF is used to solve the HOMP estimation to predict the evolution of the machine health in the form of a probability density function (PDF). An on-line model update scheme is developed to adapt the Markov process changes to machine health dynamics quickly. The experimental results on a bearing test-bed illustrate the potential applications of the proposed system as an effective and simple tool for machine health prognostics.
Risk factors for in-hospital post-hip fracture mortality.
Frost, Steven A; Nguyen, Nguyen D; Black, Deborah A; Eisman, John A; Nguyen, Tuan V
2011-09-01
Approximately 10% of hip fracture patients die during hospitalization; however, it is not clear what risk factors contribute to the excess mortality. This study sought to examine risk factors of, and to develop prognostic model for, predicting in-hospital mortality among hip fracture patients. We studied outcomes among 410 men and 1094 women with a hip fracture who were admitted to a major-teaching-hospital in Sydney (Australia) between 1997 and 2007. Clinical data, including concomitant illnesses, were obtained from inpatient data. The primary outcome of the study was in-hospital mortality regardless of length of stay. A Log-binomial regression model was used to identify risk factors for in-hospital mortality. Using the identified risk factors, prognostic nomograms were developed for predicting short term risk of mortality for an individual. The median duration of hospitalization was 9 days. During hospitalization, the risk of mortality was higher in men (9%) than in women (4%). After adjusting for multiple risk factors, increased risk of in-hospital mortality was associated with advancing age (rate ratio [RR] for each 10-year increase in age: 1.91 95% confidence interval [CI]: 1.47 to 2.49), in men (RR 2.13; 95% CI 1.41 to 3.22), and the presence of comorbid conditions on admission (RR for one or more comorbid conditions vs. none: 2.30; 95% CI 1.52 to 3.48). Specifically, the risk of mortality was increased in patients with a pre-existing congestive heart failure (RR 3.02; 95% CI: 1.65 to 5.54), and liver disease (RR 4.75; 95% CI: 1.87 to 12.1). These factors collectively accounted for 69% of the risk for in-hospital mortality. A nomogram was developed from these risk factors to individualize the risk of in-hospital death following a hip fracture. The area under the receiver operating characteristic curve of the final model containing age, sex and comorbid conditions was 0.76. These data suggest that among hip fracture patients, advancing age, gender (men), and pre-existing concomitant diseases such as congestive heart failure and liver disease were the main risk factors for in-hospital mortality. The nomogram developed from this study can be used to convey useful prognostic information to help guide treatment decisions. Copyright © 2011 Elsevier Inc. All rights reserved.
Prognostic value of serum heavy/light chain ratios in patients with POEMS syndrome.
Wang, Chen; Su, Wei; Cai, Qian-Qian; Cai, Hao; Ji, Wei; Di, Qian; Duan, Ming-Hui; Cao, Xin-Xin; Zhou, Dao-Bin; Li, Jian
2016-07-01
POEMS syndrome is a rare plasma cell dyscrasia. Serum concentrations of the monoclonal protein in this disorder are typically low, and inapplicable to monitor disease activity in most cases, resulting in limited practical and prognostic values. Novel immunoassays measuring isotype-specific heavy/light chain (HLC) pairs showed its utility in disease monitoring and outcome prediction in several plasma cell dyscrasias. We report results of HLC measurements in 90 patients with POEMS syndrome. Sixty-six patients (73%; 95% confidence interval, 63-82%) had an abnormal HLC ratio at baseline. It could stratify the risk of disease relapse and was strongly associated with worse progression-free survival in a multivariate analysis (P = 0.021; hazard ratio [HR] 6.89, 95% CI 1.34-35.43). After therapy, HLC ratios improved, with 43 patients (48%) remaining abnormal. The post-therapeutic HLC ratio, if abnormal, also remained as an independent prognostic factor associated with worse progression-free survival (P = 0.019; HR 4.30, 95% CI 1.27-14.56). These results suggest the prognostic utility of HLC ratios in clinical management of POEMS patients. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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.
Prognostic Impact of PHIP Copy Number in Melanoma: Linkage to Ulceration
Nosrati, Mehdi; Tong, Schuyler; Wu, Clayton; Thummala, Suresh; Dar, Altaf A.; Leong, Stanley P.L.; Cleaver, James E.; Sagebiel, Richard W.; Miller, James R.; Kashani-Sabet, Mohammed
2013-01-01
Ulceration is an important prognostic factor in melanoma whose biologic basis is poorly understood. Here we assessed the prognostic impact of pleckstrin homology domain-interacting protein (PHIP) copy number and its relationship to ulceration. PHIP copy number was determined using fluorescence in situ hybridization (FISH) in a tissue microarray cohort of 238 melanomas. Elevated PHIP copy number was associated with significantly reduced DMFS (P = 0.01) and DSS (P = 0.009) by Kaplan-Meier analyses. PHIP FISH scores were independently predictive of DMFS (P = 0.03) and DSS (P = 0.03). Increased PHIP copy number was an independent predictor of ulceration status (P = 0.04). The combined impact of increased PHIP copy number and tumor vascularity on ulceration status was highly significant (P< 0.0001). Stable suppression of PHIP in human melanoma cells resulted in significantly reduced glycolytic activity in vitro, with lower expression of LDH5, HIF1A, and VEGF, and was accompanied by reduced microvessel density in vivo. These results provide further support for PHIP as a molecular prognostic marker of melanoma, and reveal a significant linkage between PHIP levels and ulceration. Moreover, they suggest that ulceration may be driven by increased glycolysis and angiogenesis. PMID:24005052
Vikhireva, Olga; Broda, Grazyna; Kubinova, Ruzena; Malyutina, Sofia; Pająk, Andrzej; Tamosiunas, Abdonas; Skodova, Zdena; Simonova, Galina; Bobak, Martin; Pikhart, Hynek
2014-01-01
The SCORE scale predicts the 10-year risk of fatal atherosclerotic cardiovascular disease (CVD), based on conventional risk factors. The high-risk version of SCORE is recommended for Central and Eastern Europe and former Soviet Union (CEE/FSU), due to high CVD mortality rates in these countries. Given the pronounced social gradient in cardiovascular mortality in the region, it is important to consider social factors in the CVD risk prediction. We investigated whether adding education and marital status to SCORE benefits its prognostic performance in two sets of population-based CEE/FSU cohorts. The WHO MONICA (MONItoring of trends and determinants in CArdiovascular disease) cohorts from the Czech Republic, Poland (Warsaw and Tarnobrzeg), Lithuania (Kaunas), and Russia (Novosibirsk) were followed from the mid-1980s (577 atherosclerotic CVD deaths among 14,969 participants with non-missing data). The HAPIEE (Health, Alcohol, and Psychosocial factors In Eastern Europe) study follows Czech, Polish (Krakow), and Russian (Novosibirsk) cohorts from 2002-05 (395 atherosclerotic CVD deaths in 19,900 individuals with non-missing data). In MONICA and HAPIEE, the high-risk SCORE ≥5% at baseline strongly and significantly predicted fatal CVD both before and after adjustment for education and marital status. After controlling for SCORE, lower education and non-married status were significantly associated with CVD mortality in some samples. SCORE extension by these additional risk factors only slightly improved indices of calibration and discrimination (integrated discrimination improvement <5% in men and ≤1% in women). Extending SCORE by education and marital status failed to substantially improve its prognostic performance in population-based CEE/FSU cohorts.
Suh, Young Joo; Lee, Hyun-Ju; Kim, Young Tae; Kang, Chang Hyun; Park, In Kyu; Jeon, Yoon Kyung; Chung, Doo Hyun
2018-06-01
Our study investigates the added value of computed tomography (CT) characteristics, histologic subtype classification of the International Association for the Study of Lung Cancer (IASLC)/the American Thoracic Society (ATS)/the European Respiratory Society (ERS), and genetic mutation for predicting postoperative prognoses of patients who received curative surgical resections for lung adenocarcinoma. We retrospectively enrolled 988 patients who underwent curative resection for invasive lung adenocarcinoma between October 2007 and December 2013. Cox's proportional hazard model was used to explore the risk of recurrence-free survival, based on the combination of conventional prognostic factors, CT characteristics, IASLC/ATS/ERS histologic subtype, and epidermal growth factor receptor (EGFR) mutations. Incremental prognostic values of CT characteristics, histologic subtype, and EGFR mutations over conventional risk factors were measured by C-statistics. During median follow-up period of 44.7 months (25th to 75th percentile 24.6-59.7 months), postoperative recurrence occurred in 248 patients (25.1%). In univariate Cox proportion hazard model, female sex, tumor size and stage, CT characteristics, and predominant histologic subtype were associated with tumor recurrence (P < 0.05). In multivariate Cox regression model adjusted for tumor size and stage, both CT characteristics and histologic subtype were independent tumor recurrence predictors (P < 0.05). Cox proportion hazard models combining CT characteristics or histologic subtype with size and tumor stage showed higher C-indices (0.763 and 0.767, respectively) than size and stage-only models (C-index 0.759, P > 0.05). CT characteristics and histologic subtype have relatively limited added prognostic values over tumor size and stage in surgically resected lung adenocarcinomas. Copyright © 2018 Elsevier B.V. All rights reserved.