scholarly journals Gene-Gene Interaction Analysis for the Survival Phenotype Based on the Kaplan-Meier Median Estimate

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Mira Park ◽  
Jung Wun Lee ◽  
Taesung Park ◽  
SeungYeoun Lee
Keyword(s):  
Survival Time ◽  
Median Survival ◽  
Median Survival Time ◽  
Interaction Analysis ◽  
Computing Time ◽  
Gene Interaction ◽  
Risk Groups ◽  
The Cancer Genome Atlas ◽  
Rank Test ◽  
Kaplan Meier

In this study, we propose a simple and computationally efficient method based on the multifactor dimensional reduction algorithm to identify gene-gene interactions associated with the survival phenotype. The proposed method, referred to as KM-MDR, uses the Kaplan-Meier median survival time as a classifier. The KM-MDR method classifies multilocus genotypes into a binary attribute for high- or low-risk groups using median survival time and replaces balanced accuracy with log-rank test statistics as a score to determine the best model. Through intensive simulation studies, we compared the power of KM-MDR with that of Surv-MDR, Cox-MDR, and AFT-MDR. It was found that KM-MDR has a similar power to that of Surv-MDR, with less computing time, and has comparable power to that of Cox-MDR and AFT-MDR, even when there is a covariate effect. Furthermore, we apply KM-MDR to a real dataset of ovarian cancer patients from The Cancer Genome Atlas (TCGA).

scholarly journals Identification of the Novel Methylated Genes’ Signature to Predict Prognosis in INRG High-Risk Neuroblastomas

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Zhichao Liu ◽  
Changchun Li
Keyword(s):  
Regression Analysis ◽  
High Risk ◽  
Survival Time ◽  
Median Survival ◽  
Median Survival Time ◽  
Test Group ◽  
Functional Enrichment ◽  
Rank Test ◽  
Cox Regression Analysis ◽  
Log Rank Test

Background. Neuroblastomas are the most frequent extracranial pediatric solid tumors. The prognosis of children with high-risk neuroblastomas has remained poor in the past decade. A powerful signature is required to identify factors associated with prognosis and improved treatment selection. Here, we identified a strong methylation signature that favored the earlier diagnosis of neuroblastoma in patients. Methods. Gene methylation (GM) data of neuroblastoma patients from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) were analyzed using a multivariate Cox regression analysis (MCRA) and univariate Cox proportional hazards regression analysis (UCPHRA). Results. The methylated genes’ signature consisting of eight genes (NBEA, DDX28, TMED8, LOC151174, EFNB2, GHRHR, MIMT1, and SLC29A3) was selected. The signature divided patients into low- and high-risk categories, with statistically significant survival rates (median survival time: 25.08 vs. >128.80 months, log-rank test, P < 0.001 ) in the training group, and the validation of the signature’s risk stratification ability was carried out in the test group (log-rank test, P < 0.01 , median survival time: 30.48 vs. >120.36 months). The methylated genes’ signature was found to be an independent predictive factor for neuroblastoma by MCRA. Functional enrichment analysis suggested that these methylated genes were related to butanoate metabolism, beta-alanine metabolism, and glutamate metabolism, all playing different significant roles in the process of energy metabolism in neuroblastomas. Conclusions. The set of eight methylated genes could be used as a new predictive and prognostic signature for patients with INRG high-risk neuroblastomas, thus assisting in treatment, drug development, and predicting survival.

scholarly journals Controlling Nutritional Status (CONUT) Score is Associated with Overall Survival in Patients with Unresectable Hepatocellular Carcinoma Treated with Lenvatinib: A Multicenter Cohort Study

Nutrients ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 1076 ◽  
Author(s):  
Shigeo Shimose ◽  
Takumi Kawaguchi ◽  
Hideki Iwamoto ◽  
Masatoshi Tanaka ◽  
Ken Miyazaki ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Nutritional Status ◽  
Survival Time ◽  
Median Survival ◽  
Median Survival Time ◽  
Rank Test ◽  
Multicenter Cohort Study ◽  
The Impact ◽  
Conut Score

We aimed to investigate the impact of the controlling nutritional status (CONUT) score, an immuno-nutritional biomarker, on the prognosis of patients with hepatocellular carcinoma (HCC) treated with lenvatinib (LEN). This retrospective study enrolled 164 patients with HCC and treated with LEN (median age 73 years, Barcelona Clinic Liver Cancer (BCLC) stage B/C 93/71). Factors associated with overall survival (OS) were evaluated using multivariate and decision tree analyses. OS was calculated using the Kaplan–Meier method and analyzed using the log–rank test. Independent factors for OS were albumin–bilirubin grade 1, BCLC stage B, and CONUT score <5 (hazard ratio (HR) 2.9, 95% confidence interval (CI) 1.58–5.31, p < 0.001). The CONUT score was the most important variable for OS, with OS rates of 70.0% and 29.0% in the low and high CONUT groups, respectively. Additionally, the median survival time was longer in the low CONUT group than in the high CONUT group (median survival time not reached vs. 11.3 months, p < 0.001). The CONUT score was the most important prognostic variable, rather than albumin–bilirubin grade and BCLC stage, in patients with HCC treated with LEN. Accordingly, immuno-nutritional status may be an important factor in the management of patients with HCC treated with LEN.

Liver metastases of colorectal carcinoma: Prospective study on the use of transarterial chemoembolization (TACE)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4062-4062
Author(s):  
T. J. Vogl ◽  
T. Gruber ◽  
S. Zangos ◽  
J. O. Balzer
Keyword(s):  
Colorectal Cancer ◽  
Survival Rate ◽  
Liver Metastases ◽  
Survival Time ◽  
Cancer Patients ◽  
Median Survival ◽  
Local Control ◽  
Median Survival Time ◽  
Kaplan Meier ◽  
Colorectal Cancer Patients

4062 Background: To evaluate the efficacy of chemoembolization (TACE) in the treatment of liver metastases in colorectal cancer patients concerning local control and survival. Methods: 207 patients with liver metastases of colorectal cancer were treated with repeated TACE in 4-week intervals. In total, 1,307 chemoembolizations were performed with a mean of 6.3 sessions per patient. At the time of first chemoembolization the average age of the patients was 68.8 years (range, 39.4–83.5 years). 158 patients were treated palliatively, 35 symptomatically and 14 patients neoadjuvantly. The chemotherapy consisted of Mitomycin C with/without Gemcitabin; embolization was performed with Lipiodol and starch microspheres for vessel occlusion. Tumor response was evaluated by magnetic resonance imaging (MRI). The change in size was calculated and the response was evaluated according to the RECIST criteria. Survival rates from the first diagnosis and from the first TACE session were both calculated according to the Kaplan-Meier method to obtain the median survival. Results: While 70% of the patients showed multiple metastases, 6% had 1 metastasis, 5.8% had 2 metastases and 18.2% had 3 to 4 metastases. Lesion size and number before, during and after treatment were assessed to deduce the morphological response. Local control results according to the RECIST criteria were as follows: partial response 12% of patients, stable disease in 51% and progressive disease in 37%. The 1-year survival rate after TACE was 62%, but the 2-year survival rate had been reduced to 38%. The median survival time from the date of diagnosis of metastases was 3.4 years (according to Kaplan-Meier), the median survival time from the start of TACE treatment was 1.34 years. The median survival time of the palliative group was 1.4 years, of the symptomatic group 0.8 years and of the neoadjuvant group 1.5 years. Conclusions: TACE is an effective minimal-invasive therapy for neoadjuvant, symptomatic or palliative treatment of liver metastases in colorectal cancer patients. No significant financial relationships to disclose.

Clinical Outcome of 40 Patients with Higher-Risk Myelodysplastic Syndromes (MDS) after Treatment with Hypomethylating Agents: a Matched-Pairs Analysis

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2687-2687
Author(s):  
Kathrin Nachtkamp ◽  
Corinna Strupp ◽  
Andrea Kuendgen ◽  
Norbert Gattermann ◽  
Rainer Haas ◽  
...  
Keyword(s):  
High Risk ◽  
Survival Time ◽  
Median Survival ◽  
Median Survival Time ◽  
Survival Benefit ◽  
Low Dose ◽  
Phase Iii ◽  
Matched Pairs ◽  
Hypomethylating Agents ◽  
Kaplan Meier

Abstract Introduction: Patients with higher-risk MDS, especially those with an IPSS score of intermediate-2 or high, face a very poor prognosis with a median survival of 12 to 18 months. Allogeneic transplantation as a curative approach is an option for only a small percentage of patients. In phase-III-trials, hypomethylating agents demonstrated a survival benefit for this patient group. In order to validate the use of these compounds in clinical day-to-day practice, we analyzed 40 patients who underwent hypomethylating treatment with either decitabine or 5-azacytidine. Methods: We performed matched-pairs analyses using the Düsseldorf MDS registry (n=3288). Patients with higher-risk MDS (INT-1, INT-2, or high-risk IPSS scores) at the time of treatment with hypomethylating agents (n=40) were compared with higher-risk MDS patients who received best supportive care (BSC) only (n=120) and with higher-risk MDS patients who underwent treatment with low-dose Ara-C (n=35). Patients were matched according to age, gender, WHO type, IPSS score and date of diagnosis. Each patient in the hypomethylating cohort was matched with three patients of the BSC cohort and one patient of the low-dose ara-C cohort. For 5 patients, no adequate match partner of the low-dose ara-C cohort could be assigned. Follow-up for survival was assured by contacting our outpatient department or primary care physician. Results: The distribution of WHO types at time of diagnosis within the decitabine/5-azacytidine cohort was 10 RA/RCMD patients, 9 RAEB I, 16 RAEB II, 2 CMML I and 3 CMML II. Median age was 70 years. 10 patients belonged to the intermediate-1, 11 to the intermediate-2 and 18 patients to the high-risk group according to the IPSS score. In one patient, the IPSS score could not be assessed. All patients had progressed to at least RAEB II when treatment was initiated. 19 patients received decitabine and 21 patients were given 5-azacytidine. Median survival time in the hypomethylating cohort was 28 months, regardless of the type of hypomethylating treatment, compared with 10 months in the BSC cohort. Figure 1 shows the Kaplan Meier curve comparing 40 patients treated with hypomethylating agents with 120 patients who received BSC only (p=0.0026). Median survival time of the low-dose ara-C cohort was 20 months; although 5 patients of the hypomethylating cohort could not be assigned a match partner and therefore had to be withdrawn from the comparison with low-dose ara-C, median survival in the remaining 35 patients of the hypomethylating cohort was still 28 months. Figure 2 shows the Kaplan Meier curve comparing the hypomethylating cohort with the low-dose ara-C cohort (p=0.027). Conclusions: Our data show that higher-risk MDS patients have a substantial survival benefit from treatment with hypomethylating agents as compared to both low-dose ara-C and BSC patients. Hypomethylating agents should be considered to be the treatment of choice in higher-risk MDS patients who are not candidates for allografting. Figure Figure

scholarly journals The Association of Hypertension With the Severity of and Mortality From the COVID-19 in the Early Stage of the Epidemic in Wuhan, China: A Multicenter Retrospective Cohort Study

2021 ◽  
Vol 8 ◽  
Author(s):  
Sumaira Mubarik ◽  
Xiaoxue Liu ◽  
Ehab S. Eshak ◽  
Keyang Liu ◽  
Qing Liu ◽  
...  
Keyword(s):  
Survival Time ◽  
Disease Severity ◽  
Median Survival ◽  
Median Survival Time ◽  
Early Stage ◽  
Hypertension Status ◽  
Factors Associated ◽  
Kaplan Meier ◽  
Increased Risk ◽  
Before And After

Background: Hypertension may affect the prognosis of COVID-19 illness. We analyzed the epidemiological and clinical characteristics associated with the disease severity and mortality in hypertensive vs. non-hypertensive deceased COVID-19 patients.Methods: We included all the deceased patients with laboratory-confirmed COVID-19 admitted to &gt;200 health facilities in Wuhan between December 1 and February 24, 2020. The median survival time in COVID-19 patients with and without hypertension, the association of hypertension with the disease severity, and the risk factors associated with the COVID-19 mortality stratified by the hypertension status were assessed using the Kaplan-Meier survival analysis, logistic regression, and Cox proportional regression, respectively before and after the propensity score-matching (PS) for age and sex.Results: The prevalence of hypertension in the studied 1,833 COVID-19 patients was 40.5%. Patients with hypertension were more likely to have severe COVID-19 illness than patients without hypertension; the PS-matched multivariable-adjusted odds ratio (95% CI) was 2.44 (1.77–3.08). Moreover, the median survival time in the hypertension group was 3–5 days shorter than the non-hypertension group. There was a 2-fold increased risk of COVID-19 mortality in the hypertension group compared with the non-hypertension group; the PS-matched multivariable-adjusted hazard ratio (HR) = 2.04 (1.61–2.72), and the significant increased risk of COVID-19 mortality in the moderate vs. mild COVID-19 illness was confined to patients with hypertension. Additionally, the history and the number of underlying chronic diseases, occupation, and residential location showed stronger associations with the COVID-19 mortality among patients with hypertension than patients without hypertension.Conclusion: Hypertension was associated with the severity and mortality of COVID-19 illness.

RBIO-02. THERAPEUTIC EFFECTS OF RADIOTHERAPY WITH CONCOMITANT IN CHILDREN WITH DIPG

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi191-vi192
Author(s):  
Mingyao Lai ◽  
Shaoqun Li ◽  
Juan Li ◽  
Qingjun Hu ◽  
Junjie Zhen ◽  
...  
Keyword(s):  
Survival Time ◽  
Median Survival ◽  
Median Survival Time ◽  
Proportional Hazards ◽  
Disease Recurrence ◽  
Diffuse Intrinsic Pontine Glioma ◽  
Cox Proportional Hazards ◽  
Hematological Toxicity ◽  
Therapeutic Effects ◽  
Kaplan Meier

Abstract OBJECTIVE To retrospectively analyze the therapeutic effects of radiotherapy with concomitant and adjuvant temozolomide（TMZ） versus radiotherapy with concomitant TMZ alone for pediatric diffuse intrinsic pontine glioma (DIPG), and to evaluate the value of radiotherapy and TMZ in the treatment of pediatric DIPG. METHODS The clinical data of children with confirmed DIPG in Guangdong Sanjiu Brain Hospital between January 1, 2010 and March 31, 2020 were collected. The inclusive criteria included (1) receiving a total radiotherapy dose of 54 Gy in 27 fractions, (2) treated with concomitant TMZ chemotherapy, and (3) with or without adjuvant TMZ chemotherapy. A total of 85 pediatric patients were eligible for the study. The Kaplan-Meier method was used for survival analysis, and a multivariable Cox proportional hazards regression model was used to assess the independent prognostic factors. RESULTS Among 85 cases with a median age of 7 years (range 2-16 years), the median follow-up was 9 months (range 3-28 months) and the median survival time was 9 months. The median survival time of 66 patients treated with radiotherapy with concomitant and adjuvant TMZ was 10 months, longer than 6 months of the other 19 patients treated with radiotherapy with concomitant TMZ alone, with statistical differences (p=0.002). Moreover, bevacizumab and nimotuzumab didn't bring survival benefits to patients with disease recurrence or progression. The prognosis in DIPG patients with H3K27M positive expressed is poor. Hematological toxicity (Grade IV) was not found. CONCLUSION Radiotherapy with concomitant and adjuvant TMZ prolongs the survival time of children with DIPG.

scholarly journals Evaluation of the value of preoperative CYFRA21-1 in the diagnosis and prognosis of epithelial ovarian cancer in conjunction with CA125

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Chunjing Jin ◽  
Minfeng Yang ◽  
Xueqiao Han ◽  
Haidan Chu ◽  
Yan Zhang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Survival Time ◽  
Median Survival ◽  
Median Survival Time ◽  
Cytokeratin 19 ◽  
Tumor Biomarker ◽  
Diagnostic Efficiency ◽  
Poor Prognostic Factor ◽  
Kaplan Meier

AbstractGrowing evidence indicates that the tumor biomarker cytokeratin 19 fragment (CYFRA21-1) is significant for a variety of cancers. However, its role in epithelial ovarian cancer (EOC) has rarely been reported. In this study, a receiver operating characteristic (ROC) curve was utilized to estimate the diagnostic efficiency of CYFRA21-1. The correlation between the CYFRA21-1 level and prognosis was analyzed by Kaplan-Meier survival analysis and univariable and multivariable analyses. The relationship between serum CYFRA21-1 levels and different clinicopathological variables was also analyzed. At the same time, the standard serum marker cancer antigen 125 (CA125) was measured. The results demonstrated that CYFRA21-1 expression was significantly increased in EOC compared with expression in benign ovarian diseases and healthy controls, which was similar to CA125 (P < 0.001). CYFRA21-1 expression was positively correlated with CA125 (r = 0.201; P = 0.0032). CYFRA21-1 expression was significantly correlated with lymph node metastasis and ascites (P < 0.001). Furthermore, the median survival time of EOC patients with high CYFRA21-1 expression was 42 months, compared with 54 months in the low CYFRA21-1 expression patients by Kaplan-Meier analysis (P < 0.05), while the high and low CA125 expression groups had no difference in median survival time. Univariate and multivariate analyses indicated that CYFRA21-1 was a poor prognostic factor associated with overall survival (OS), while CA125 was not. Our study indicates that CYFRA21-1 acts as a good complementary diagnostic biomarker and may be superior to CA125 as a prognostic indicator in EOC.

Significance of cytogenetic clonal evolution in chronic myelogenous leukemia.

1996 ◽  
Vol 14 (1) ◽  
pp. 196-203 ◽  
Author(s):  
A Majlis ◽  
T L Smith ◽  
M Talpaz ◽  
S O'Brien ◽  
M B Rios ◽  
...  
Keyword(s):  
Survival Time ◽  
Chronic Myelogenous Leukemia ◽  
Median Survival ◽  
Median Survival Time ◽  
Interferon Therapy ◽  
Clonal Evolution ◽  
Prognostic Significance ◽  
Risk Groups ◽  
Myelogenous Leukemia ◽  
Chromosome 17

PURPOSE To describe the incidence and significance of clonal evolution patterns. PATIENTS AND METHODS We analyzed 264 patients with Philadelphia chromosome (Ph)-positive chronic myelogenous leukemia (CML) who developed clonal evolution between 1967 and 1993. RESULTS The median survival time following clonal evolution was 19 months. Factors associated with worse survival (P < .01) were as follows: chromosome 17 abnormality or chromosomal translocations other than Ph, high percentage of abnormal metaphases, longer time to clonal evolution, and presence of other accelerated-phase features. A recursive partitioning technique (CART) identified different risk groups. The best group (37 patients; no chromosome 17 abnormality, abnormal metaphases < 16%, and interval to clonal evolution < or = 24 months) had an estimated median survival time of 54 months. The worst two groups included 27 patients with chromosome 17 abnormalities and > or = 36% abnormal metaphases (estimated median survival time, 6 months), and 22 patients with other accelerated features and > or = 16% abnormal metaphases (estimated median survival time, 7 months). The intermediate group had an estimated median survival time that ranged from 13 to 24 months. Prior interferon therapy evaluated within risk groups showed a significant survival advantage only in the intermediate-risk group. A multivariate analysis showed similar results, and identified the following independent poor prognostic variables: chromosome 17 abnormality, percentage of abnormal metaphases (cutoff, 24%), longer time to clonal evolution (cutoff, 24 months), other accelerated-phase features, and no prior interferon therapy. Patients with none, one, two, three, or more of the first four features had median survivals times of 51, 24, 14, and 7 months, respectively. CONCLUSION The prognostic significance of clonal evolution in CML is not uniform and is related to the specific abnormality, time to its development, its predominance in metaphases, and the presence of other accelerated features, and it may be modified by specific therapies.

scholarly journals Predictors of survival after second surgery for recurrent glioblastoma tumours

2015 ◽  
Vol 42 (S1) ◽  
pp. S46-S46
Author(s):  
A Kilian ◽  
K Parvez ◽  
E Monsalves ◽  
S Larjani ◽  
G Klironomos ◽  
...  
Keyword(s):  
Survival Time ◽  
Median Survival ◽  
Median Survival Time ◽  
Chart Review ◽  
Elective Surgery ◽  
Retrospective Chart Review ◽  
Recurrent Glioblastoma ◽  
Kaplan Meier ◽  
Second Surgery ◽  
The Impact

Background: The impact of second surgery on recurrence remains unclear, with few definitive studies to date. This study sought to identify major predictors of survival after second surgery. Methods: A retrospective chart review was conducted for 21 patients who underwent elective surgery for GBM recurrence, at our institution, in the past 6 years. Kaplan Meier was applied to determine the significance of the variables on survival time. The Mann Whitney U test was used to determine whether the median survival time differed significantly between groups, for the factors of interest. Results: Among variables examined, age, less than ≥50 (P=0.04) was significant. Patients younger than 50, had a median survival period of 11.8 months, while patients, age 50 or older, survived a median time of 4.2 months. Though chemotherapy after reoperation was not found to statistically significantly extend survival time on Kaplan-Meier (P=0.08), the median survival time was found to be significantly higher in patients that received chemotherapy (10.6 months) after reoperation, compared with those who did not (3.9 months), using the Mann Whitney U test (P=0.05). Conclusions: These results confirm that younger patients survive longer after second surgery and indicate that a second round of chemotherapy may prolong survival.

Phase I to II Study of Pleurectomy/Decortication and Intraoperative Intracavitary Hyperthermic Cisplatin Lavage for Mesothelioma

2006 ◽  
Vol 24 (10) ◽  
pp. 1561-1567 ◽  
Author(s):  
William G. Richards ◽  
Lambros Zellos ◽  
Raphael Bueno ◽  
Michael T. Jaklitsch ◽  
Pasi A. Jänne ◽  
...  
Keyword(s):  
Relative Risk ◽  
Survival Time ◽  
Median Survival ◽  
Median Survival Time ◽  
Sodium Thiosulfate ◽  
Postoperative Mortality ◽  
Maximum Tolerated Dose ◽  
Rank Test ◽  
High Dose ◽  
Epithelial Tumors

Purpose To evaluate morbidity, mortality, maximum-tolerated dose (MTD), and outcome of intraoperative intracavitary hyperthermic cisplatin lavage in patients undergoing pleurectomy for malignant pleural mesothelioma (MPM). Patients and Methods Sixty-one patients were prospectively registered. Forty-four resectable patients with MPM underwent pleurectomy, followed by a 1-hour lavage of the resection cavity with dose-escalated cisplatin (50, 100, 150, 175, 200, 225, and 250 mg/m2) at 42°C and then intravenous sodium thiosulfate (16 g/m2 over 6 hours). Survival estimates were compared using the log-rank test and proportional hazards regression. Results Median age was 71 years (range, 50 to 82 years). Twenty-four patients had epithelial tumors, and 20 had sarcomatous or mixed histology. Postoperative mortality was 11% (five of 44 patients). Dose-limiting renal toxicity occurred at 250 mg/m2, establishing the MTD at 225 mg/m2. Other morbidity included atrial fibrillation (14 of 44 patients, 32%) and deep venous thrombosis (four of 44 patients, 9%). Median survival time of all registered patients was 9 months, and the median survival time of resected patients was 13 months. Survival estimates differed significantly for resectable patients exposed to low doses (50 to 150 mg/m2; n = 9; median, 6 months) versus high doses (175 to 250 mg/m2; n = 35; median, 18 months) of hyperthermic cisplatin (P = .0019); recurrence-free interval also differed significantly (4 v 9 months, respectively; P < .0001). Low dose level (relative risk = 3.418) and nonepithelial histology (relative risk = 2.336) were independent risk factors for poor survival. Twenty patients with epithelial tumors who underwent high-dose cisplatin lavage had a 26-month median survival time. Conclusion Pleurectomy and high-dose intraoperative intracavitary hyperthermic cisplatin lavage is feasible in this patient population with restricted surgical options. An apparent dose-related survival benefit warrants further study.

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