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Shorter Progression-free Survival (shorter + progression-free_survival)
Selected AbstractsChromosome 1p21 deletion is a novel prognostic marker in patients with multiple myelomaBRITISH JOURNAL OF HAEMATOLOGY, Issue 1 2007Hong Chang Summary The combination of fluorescence in situ hybridization with cytoplasmic light chain detection identified chromosome 1p21 deletion in 18 (20%) of 87 patients with multiple myeloma. 1p21 deletion was associated with higher serum calcium level, 13q deletion, and t(4;14). Patients with 1p21 deletions had a significantly shorter progression-free survival (PFS) (median 10·5 vs. 22·3 months, P = 0·0002) and shorter overall survival (OS) (median 33·9 months vs. not reached, P = 0·002) than those without 1p21 deletions. On multivariate analysis, which included deletions of 13q, TP53, t(4;14) and CKS1B amplification, 1p21 deletion remained as an independent risk factor for PFS (P = 0·01) and OS (P = 0·04). [source] Multiple myeloma patients with CKS1B gene amplification have a shorter progression-free survival post-autologous stem cell transplantationBRITISH JOURNAL OF HAEMATOLOGY, Issue 4 2006Hong Chang Summary The prevalence and prognostic relevance of recurrent gains of CKS1B (cyclin kinase subunit 1B) gene at chromosome 1q21 region was investigated by interphase fluorescence in situ hybridisation in a cohort of 99 multiple myeloma (MM) patients treated with intensive chemotherapy followed by autologous stem cell transplantation. CKS1B amplification (3,8 CKS1B signals) was detected in 31of 99 (31%) patients and was associated with deletions of p53 (P = 0·003) and 13q (P = 0·039) but not with translocation t(11;14) or t(4;14). CKS1B amplification was associated with bone marrow plasmacytosis (P = 0·02), but there was no correlation with patient age, gender, disease stage, lytic bone lesions, albumin, creatinine, C-reactive protein or beta-2 microglobulin levels. Patients with CKS1B amplification had a significantly shorter progression-free survival than those without such amplification (18·5 vs. 25·7 months, P = 0·035). Likewise, a shorter overall survival (44·8 months vs. not reached) was observed; however, the difference did not reach statistical significance (P = 0·20). Seven patients had paired bone marrows obtained at diagnosis and at relapse, the percentage of cells with CKS1B amplification and the level of amplification were significantly increased in the relapse marrows. In this cohort of patients, CKS1B was frequently amplified in MM and may represent genetic instability associated with disease progression. [source] Association of p53 codon 72 polymorphism and MDM2 SNP309 with clinical outcome of advanced nonsmall cell lung cancerCANCER, Issue 4 2008Ji-Youn Han MD Abstract BACKGROUND. The purpose of the study was to investigate whether polymorphisms of p53 codon 72 (Arg72Pro) and MDM2 SNP309 (309T>G) affect p53 expression and the clinical outcome of patients with advanced nonsmall cell lung cancer (NSCLC). METHODS. A total of 148 NSCLC patients, previously enrolled in 2 different prospective clinical trials, were genotyped for the p53 Arg72Pro and MDM2 309T>G polymorphisms. Immunohistochemical staining of p53 protein was performed on 61 tumor samples. Genotypes were correlated with p53 expression, clinicopathologic factors, tumor response, and survival. Multivariate logistic or Cox regression analyses were used to adjust for possible confounding variables. RESULTS. The distribution of sex, age, performance status, stage, tumor histology, and smoking habit was not significantly different among polymorphism variants. However, a significant association was observed between p53 Arg72Pro polymorphism and primary resistance to chemotherapy. Patients with the Pro/Pro variant were more likely to be resistant to first-line chemotherapy, especially the irinotecan plus cisplatin regimen, than those with Arg/Arg or Arg/Pro variants (60% vs 27%, P = .014). In multivariate analysis, the Pro/Pro genotype was strongly predictive for shorter progression-free survival (PFS) (hazard ratio [HR] = 1.952, P = .01). The p53 overexpression was associated with MDM2 SNP309. The TT genotype showed more p53 overexpression than TG or GG genotypes (P = .036). In multivariate analysis, the MDM2 TT genotype was independently predictive for longer survival (HR = 1.742, P = .032). CONCLUSIONS. The p53 72Pro/Pro variant was predictive for primary resistance to chemotherapy and shorter progression-free survival. The MDM2 SNP309 was associated with less p53 overexpression and prognostic for worse survival. Genotyping these polymorphisms may be useful for predicting the clinical outcome of advanced NSCLC. Cancer 2008. © 2008 American Cancer Society. [source] The prognostic value of hemoglobin change after initiating androgen-deprivation therapy for newly diagnosed metastatic prostate cancerCANCER, Issue 3 2006A Multivariate Analysis of Southwest Oncology Group Study 889 Abstract BACKGROUND. The objective of this study was to characterize changes in hemoglobin (HGB) levels after the initiation of androgen-deprivation therapy (ADT) in patients with previously untreated, metastatic prostate cancer who were enrolled in a large clinical trial. METHODS. The multivariate associations between 3-month change in HGB and baseline characteristics were evaluated with a linear regression model. The associations between 3-month change in HGB level and time-to-event outcomes, including overall survival and progression-free survival, were evaluated by using proportional hazards regression models. RESULTS. Quartiles of baseline HGB levels were ,12.0 g/dL, from 12.1 to 13.7 g/dL, from 13.8 to 14.7 g/dL, and >14.7 g/dL. Overall, 3 months after initiating ADT, the mean HGB level declined 0.54 g/dL (standard deviation [SD], 1.68 g/dL); however, the mean HGB level increased by 0.99 g/dL (SD, 1.83 g/dL) in patients who had baseline HGB levels <12 g/dL and decreased 1.04 g/dL (SD, 1.28 g/dL) in patients who had baseline HGB levels ,12 g/dL. After adjusting for potential confounders, including baseline HGB level, a decline in HGB after 3 months of ADT was associated independently with shorter survival (hazards ratio [HR], 1.10 per 1 g/dL decline; P = .0035) and shorter progression-free survival (HR, 1.08 per 1 g/dL decline; P = .013). An unexpected finding was that the effect of baseline HGB on overall and progression-free survival varied significantly by race. CONCLUSIONS. In a sample of men with newly diagnosed, metastatic prostate cancer, a decline in HGB level after 3 months of ADT was associated with shorter survival and progression-free survival after adjusting for disease status and other baseline covariates. Although race alone was not a strong predictor of death or disease progression, the effect of the baseline HGB level on overall and progression-free survival varied significantly by race. Cancer 2006. © 2006 American Cancer Society. [source] Gene expression profiling of advanced-stage serous ovarian cancers distinguishes novel subclasses and implicates ZEB2 in tumor progression and prognosisCANCER SCIENCE, Issue 8 2009Kosuke Yoshihara To elucidate the mechanisms of rapid progression of serous ovarian cancer, gene expression profiles from 43 ovarian cancer tissues comprising eight early stage and 35 advanced stage tissues were carried out using oligonucleotide microarrays of 18 716 genes. By non-negative matrix factorization analysis using 178 genes, which were extracted as stage-specific genes, 35 advanced stage cases were classified into two subclasses with superior (n = 17) and poor (n = 18) outcome evaluated by progression-free survival (log rank test, P = 0.03). Of the 178 stage-specific genes, 112 genes were identified as showing different expression between the two subclasses. Of the 48 genes selected for biological function by gene ontology analysis or Ingenuity Pathway Analysis, five genes (ZEB2, CDH1, LTBP2, COL16A1, and ACTA2) were extracted as candidates for prognostic factors associated with progression-free survival. The relationship between high ZEB2 or low CDH1 expression and shorter progression-free survival was validated by real-time RT-PCR experiments of 37 independent advanced stage cancer samples. ZEB2 expression was negatively correlated with CDH1 expression in advanced stage samples, whereas ZEB2 knockdown in ovarian adenocarcinoma SKOV3 cells resulted in an increase in CDH1 expression. Multivariate analysis showed that high ZEB2 expression was independently associated with poor prognosis. Furthermore, the prognostic effect of E-cadherin encoded by CDH1 was verified using immunohistochemical analysis of an independent advanced stage cancer samples set (n = 74). These findings suggest that the expression of epithelial,mesenchymal transition-related genes such as ZEB2 and CDH1 may play important roles in the invasion process of advanced stage serous ovarian cancer. (Cancer Sci 2009) [source] | ||||||||||