TERT rs2853669 as predictor for overall survival in patients with acute myeloid leukemia

IntroductionObjectiv. To investigate the contribution of TERT rs2736100 and rs2853669 gene polymorphisms in defining the genetic predisposition to AML, their association with different prognostic markers and their impact on survival, outcome and the prognosis of affected patients. Also, we investigated the association of TERT SNPs in AML in the presence or absence of DNMT3A (R882), NPM1 and FLT3 mutations.Material and methodsA total of 509 participants were enrolled in our study, consisting of 146 AML patients and 363 healthy participants, with no history of malignancy. TERT rs2736100 and rs2853669 polymorphisms were genotyped by using TaqMan SNP genotyping assays FLT3 (ITD, D835), DNMT3A (R882) and NPM1 c.863_864insTCTG (type A) mutation status was analyzed in each AML case.ResultsTERT rs2736100 and rs2853669 were not associated with AML risk in the codominant, dominant, recessive or allelic models. Multivariate Cox regression showed that TERT rs2853669 was a significant predictor for overall survival in AML patients. After adjusting for age, gender, cytogenetic risk group, ECOG status, FTLT3, DNM3A or NMP1 mutation, AML subtype and treatment, the estimated adjusted hasard ratio (HR adjusted=1.54, 95%CI:[1.01;2.35]) showed that the TERT rs2853669 variant genotype had a negative influence on survival time.ConclusionsTERT rs2853669 and rs2736100 polymorphisms were not risk factors for developing AML in the Romanian population, but TERT rs2853669 variant genotype had a negative effect on AML patients overall survival in the presence of other known prognostic factors.

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TP53 Alterations In CLL - Parameters Influencing The Prognostic Impact: A Study On 3,988 Patients

Blood ◽

10.1182/blood.v122.21.865.865 ◽

2013 ◽

Vol 122 (21) ◽

pp. 865-865

Author(s):

Claudia Haferlach ◽

Frank Dicker ◽

Sabine Jeromin ◽

Sandra Weissmann ◽

Andreas Roller ◽

...

Keyword(s):

Cox Regression ◽

Small Subset ◽

Mutation Load ◽

Employment Equity ◽

Mutation Status ◽

Cox Regression Analysis ◽

Tp53 Mutations ◽

Entire Cohort ◽

Impact On Survival ◽

Equity Ownership

Abstract Background In CLL, the TP53 gene may be inactivated by deletion and/or mutations. Most cases with 17p deletion also carry TP53 mutations on the second allele. However, in a subset of cases only one allele seems to be disrupted by either mutation or deletion. It is still a matter of debate whether monoallelic TP53 abnormalities have the same poor prognostic effect as biallelic alterations. Further, a small subset of patients with TP53 deletions harboring mutated IGHV genes were described to exhibit a slowly progressive disease without treatment indication for years. Aims In this study, we addressed the following questions: 1. Frequency of TP53 alterations: mutation and deletion. 2. Characterization of the TP53 altered subsets with respect to IGHV mutation status, other molecular mutations and cytogenetics. 3. Impact on survival. Patients and Methods 3,988 CLL patients were analyzed by DNA sequencing for TP53 mutations and by FISH for TP53 deletion status as well as for del(13q), del(11q) and +12. IGHV mutation status was determined in 3,505 patients. Further, SF3B1 (n=1,245), MYD88 (n=1,026), XPO1 (n=1,025), NOTCH1 (n=973), and FBXW7 (n=962) were analyzed by DNA sequencing. Results 488/3,988 (12.2%) harbored a TP53 mutation (TP53mut) and 308/3,988 (7.7%) patients showed a TP53 deletion (TP53del) by FISH. 268 cases (6.7%) showed both a TP53del and a TP53mut, while 220 cases (5.5%) harbored a TP53mut only and 40 (1.0%) a TP53del only. 20.5% of TP53mut cases harbored more than one TP53mut. The frequency of TP53mut and TP53del increased significantly with age (≤40 yrs: 2.4%/2.4%; 41-50 yrs: 7.5%/4.0%; 51-60 yrs: 12.4%/6.8%; 61-70 yrs: 12.1%/8.1%; 71-80 yrs: 13.4%/9.1%; >80 yrs: 16.0%/9.9%; p=0.006 and p=0.013, respectively). In the entire cohort, 1,428/3,505 (40.7%) cases showed an unmutated and 2,077/3,505 (59.3%) a mutated IGHV status. The lowest frequency of IGHV unmutated was observed in cases without TP53 alteration (1,148/3,094; 37.1%) and the highest in patients with both TP53mut and TP53del (156/201; 77.6%). The frequency was in between in patients with TP53mut sole (106/176; 60.2%) and TP53del sole (18/34; 52.9%). Patients with both TP53mut and TP53del as well as patients with TP53del sole had a significantly shorter overall survival (OS) compared to patients with TP53mut sole or patients without TP53 alteration (OS at 5 yrs: 40.2% vs. 36.4% vs. 68.8% vs 85.4%; p<0.001; TP53mut sole vs TP53wt: p=0.003). Next, we evaluated the impact of the TP53 mutation load on survival. Therefore, we divided patients into 10 subgroups according to their mutation load (increments of 10%). The OS of patients with a mutation load <20% (n=150) did not differ from patients with TP53wt, while a mutation load ≥20% was significantly associated with shorter OS (HR: 4.9, p<0.001). An unmutated IGHV status was associated with shorter OS in the total cohort (HR: 2.3, p<0.001). In the subset of patients with TP53wt an unmutated IGHV status was also an adverse prognostic factor (OS at 5 yrs: IGHV unmutated vs mutated: 80.3% vs 88.6%, p=0.007). This was true also in cases with TP53del sole (median OS: 12 months vs not reached, p=0.001). In contrast, in patients with either TP53mut sole or both TP53mut and TP53del the IGHV status had no impact on OS. In the entire cohort univariate Cox regression analysis revealed the following parameters to be significantly associated with OS: TP53mut (HR: 4.0), TP53mut ≥20% (HR: 4.9), TP53del (HR: 7.1), IGHV unmutated (HR: 2.3), age >60 yrs (HR: 3.3), del(11q) (HR: 2.1), del(13q) sole (HR: 0.6), SF3B1mut (HR: 2.5) (for all p<0.001), and NOTCH1mut (HR: 1.6, p=0.025). Multivariate Cox regression analysis including parameters significantly associated with OS in univariate analyses revealed the following factors to be independently associated with shorter OS: TP53del (HR: 4.2, p<0.001), TP53mut ≥20% (HR: 2.4, p=0.008), age >60 yrs (HR: 2.6, p<0.001), SF3B1mut (HR: 2.4, p<0.001), and del(11q) (HR: 2.2, p=0.002). Conclusions 1. TP53 alterations were observed in 13.2% of CLL patients, 6.7% showed both a deletion and a mutation, while 1% showed a deletion only and 5.5% a mutation only. 2. Both TP53 mutations and TP53 deletions are associated with an unmutated IGHV status. 3. TP53 deletions had the most adverse impact on survival, TP53 mutations had a significant impact on OS only if the mutation load was ≥20%. A small subset of patients with TP53 deletion sole and a mutated IGHV status seems to have a favorable outcome. Disclosures: Haferlach: MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Dicker:MLL Munich Leukemia Laboratory: Employment. Jeromin:MLL Munich Leukemia Laboratory: Employment. Weissmann:MLL Munich Leukemia Laboratory: Employment. Roller:MLL Munich Leukemia Laboratory: Employment. Worseg:MLL Munich Leukemia Laboratory: Employment. Alpermann:MLL Munich Leukemia Laboratory: Employment. Kern:MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Haferlach:MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Kohlmann:MLL Munich Leukemia Laboratory: Employment. Schnittger:MLL Munich Leukemia Laboratory: Employment, Equity Ownership.

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Albumin Is a Prognostic Factor for Overall Survival in Newly Diagnosed Patients with Acute Myeloid Leukemia (AML)

Blood ◽

10.1182/blood.v118.21.4253.4253 ◽

2011 ◽

Vol 118 (21) ◽

pp. 4253-4253

Author(s):

Awais M. Khan ◽

Jeffrey E. Lancet ◽

Mohamed A. Kharfan-Dabaja ◽

Najla H Al Ali ◽

Alan F. List ◽

...

Keyword(s):

Overall Survival ◽

Serum Albumin ◽

Induction Chemotherapy ◽

Serum Albumin Level ◽

Cox Regression ◽

Albumin Level ◽

Normal Serum ◽

Newly Diagnosed ◽

Kaplan Meier ◽

History Of

Abstract Abstract 4253 Background: Hypoalbuminemia (HA) is a strong predictor of poor clinical outcomes in many medical conditions. Low serum albumin is recognized as an adverse prognostic factor in patients with neoplastic diseases such as multiple myeloma, melanoma, and colon cancer. Severe hypoalbuminemia (<3.0 g/dl) at day +90 post allogeneic hematopoietic cell transplant (AHCT) was reported as an independent predictive variable for non-relapse mortality and overall survival (Kharfan-Dabaja, et al Biol Blood Marrow Transplant 2009; 15). A separate study conducted by our group showed that in patients with relapsed and refractory AML, serum albumin < 3.5 g/dl prior to salvage chemotherapy, correlated with lower complete remission (CR) rate and inferior overall survival (OS) (Komrokji, et al ASH 2009). We examined the prognostic value of serum albumin level prior to induction chemotherapy in patients with newly diagnosed AML. Methods: Data were collected retrospectively in a cohort of newly diagnosed AML patients who received induction chemotherapy (3+ 7 regimen). The primary objective of this study is to examine the relationship between serum albumin at baseline and probability for achieving complete remission (CR) or incomplete remission (CRi) and overall survival (OS). All analyses were conducted using SPSS version 19.0. The Kaplan–Meier method was used to estimate median overall survival; chi-square test was used for comparison of categorical variables and t-test for continuous variables. Log rank test was used to compare Kaplan–Meier survival estimates between two groups and Cox regression for multivariable analysis. Results: Between November 2004 and July 2007, 135 patients who received 3+7 induction chemotherapy at Moffitt Cancer Center were included in this analysis. Patient baseline characteristics were similar between patients with baseline serum albumin < 3.5 g/dl (HA) and those with serum albumin ≥ 3.5 g/dl (no HA) with respect to age, sex, FAB subtype, history of antecedent MDS, karyotype, and chemotherapy. Patients with HA, mean age was 60 years compared to 56.5 years in non HA group. The median OS for patients with HA was 221 days (95%CI 149.5–292.5) compared to 421 days (95%CI 236.7–605) with normal serum albumin (p<0.005). (Figure-1) The CR/CRi rate was 64%% for HA and 77.6% for those with normal albumin (p=0.09). In a multivariable Cox regression analysis including age ≥ 60 years, history of MDS, karyotype, and serum albumin level at baseline; only age, karyotype and serum albumin were independent predictors of OS [Hazard ratio 0.47 (95%CI 0.31–0.71) (p<0.005) for normal serum albumin group]. Conclusion: In this cohort of patients with newly diagnosed AML, we demonstrate that hypoalbuminemia < 3.5 g/dl is an independent covariate for overall survival with conventional chemotherapy management. Serum albumin is a surrogate marker of general health, comorbidities, and performance status. The prognostic value of low serum albumin should be validated in a prospective study. Disclosures: No relevant conflicts of interest to declare.

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GATA3 somatic mutations are associated with clinicopathological features and expression profile in TCGA breast cancer patients

Scientific Reports ◽

10.1038/s41598-020-80680-9 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Fahimeh Afzaljavan ◽

Ayeh Sadat Sadr ◽

Sevtap Savas ◽

Alireza Pasdar

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Overall Survival ◽

Somatic Mutations ◽

Cox Regression ◽

Expression Profiles ◽

Clinicopathological Features ◽

Breast Cancer Patients ◽

Mutation Status ◽

Er Positive

AbstractThe effect of somatic mutations and the gene expression profiles on the prognosis is well documented in cancer research. This study was conducted to evaluate the association of GATA3 somatic mutations with tumor features, survival, and expression profiles in breast cancer. Clinicopathological information was compared between TCGA-BRCA patients with GATA3-mutant and non-mutant tumors in all patients as well as in ER-positive subgroup. Cox-regression method was used to evaluate the association of the GATA3 mutation status with overall survival time. Differential gene expression, functional annotation, and protein–protein interaction analyses were performed using edgeR, Metascape, DAVID, STRING and CytoNCA. GATA3-mutant and non-mutant samples had significantly different clinicopathological features (p < 0.05). While GATA3 mutation status was not associated with the overall survival in the entire cohort (padj = 0.52), the GATA3-wild type ER-positive cases had a better prognosis than mutant ones (padj = 0.04). GATA3 expression was higher in tumors than normal tissues. Several pathways were different between mutant and non-mutant groups (p < 0.05). Interleukin-6 was found as the highest scored gene in both comparisons (normal vs. mutant and normal vs. non-mutant groups) in the entire patient and in the ER-positive subgroup, suggesting the association of IL6 with breast tumorigenesis. These findings suggest that GATA3 mutations can be associated with several tumor characteristics and influence the pattern of gene expression. However, GATA3 mutation status seems to be a prognostic factor for the disease only in ER-positive patients.

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Factors associated with overall survival in patients with non-squamous NSCLC in New Zealand: A comparative analysis by EGFR gene mutation status

10.21203/rs.2.22721/v1 ◽

2020 ◽

Author(s):

Phyu Sin Aye ◽

Mark James McKeage ◽

Sandar Tin Tin ◽

Prashannata Khwaounjoo ◽

J Mark Elwood

Keyword(s):

Overall Survival ◽

New Zealand ◽

Cox Regression ◽

Smoking Status ◽

Performance Status ◽

Specific Gene ◽

Mutation Status ◽

Lower Survival ◽

Nsclc Patients ◽

Positive Groups

Abstract Introduction: Non-small cell lung cancer (NSCLC) is increasingly regarded as a heterogeneous group of diseases defined by specific gene mutations. Previous studies reported inconsistent results regarding the influence of epidermal growth factor receptor (EGFR) mutations on overall survival. This study assesses the effect of EGFR mutation on overall survival, and how the effects of other survival predictors are modified by EGFR mutation status, in non-squamous NSCLC patients.Methods: The study was based on a population-based cohort of 1534 non-squamous NSCLC patients who were registered in northern New Zealand between 1 February 2010 and 31 July 2017. Kaplan-Meier analyses and log-rank tests were performed to assess the overall survival among different patient groups. Cox regression survival analyses were used to explore the associations between clinico-pathological factors and overall survival in terms of EGFR mutation status. The factors included were age at diagnosis, sex, ethnicity, smoking status, performance status, metastasis status and site of tumour. Results: In this cohort, 20.2% had an EGFR mutation. The median overall survival was 0.79 years and 2.81 years in EGFR mutation-negative and mutation-positive groups respectively (log-rank p<0.0001). Metastasis status showed large and significant effects on overall survival in both EGFR mutation-negative and mutation-positive groups (hazard ratio, HR=3.6 and 3.3, respectively). In subgroup analyses by mutation status and metastasis status, overall survival decreased with an increase in age and decrease in performance status, and was lower in current smokers in all subgroups. In specific groups, females had lower survival only if mutation-positive; Māori had lower survival compared to NZ Europeans only if the disease was metastatic; and tumour site had significant effects on overall survival only in patients without metastasis. Conclusion: EGFR mutation status and metastasis are the main predictors for overall survival in non-squamous NSCLC patients in northern New Zealand. The effects of age, smoking status and performance status are similar in all subgroups, but the effects of sex, ethnicity and site of tumour vary depending on EGFR mutation and metastasis status.

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Relationship between oncogenic mutations (RAS, BRAF and PIK3CA) and tumor location and prognosis in colorectal cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e15109 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e15109-e15109

Author(s):

Daisuke Inagaki ◽

Manabu Shiozawa ◽

Tetta Satoyoshi ◽

Yosuke Atsumi ◽

Masaaki Murakawa ◽

...

Keyword(s):

Colorectal Cancer ◽

Overall Survival ◽

Braf Mutation ◽

Cox Regression ◽

Pik3ca Mutation ◽

Tumor Location ◽

Kras Mutations ◽

Mutation Status ◽

Cox Regression Analysis ◽

Oncogenic Mutation

e15109 Background: Several studies have reported that right-sided colon cancers (RCC) and left-sided colorectal cancers (LCRC) differ in several factors including genetic features. We investigated the difference in clinicopathological characteristics and oncogenic mutation status between patients with RCC and LCRC in all stages and assessed outcome. Methods: This study was a prospective, observational study. Patients were recruited from November 2014 to February 2016. Formalin-fixed paraffin-embedded tissue blocks were collected and DNA wes extracted from tissue sections from 227 cases. There was no double cancer. Mutations in KRAS, NRAS, HRAS, BRAF and PIK3CA were detected by next-generation DNA sequencer. Tumors from cecum to transverse colon were defined as RCC, and tumors from descending colon to rectum were defined as LCRC. The median follow-up period was 521 days. Results: KRAS, NRAS, BRAF and PIK3CA mutations were present in 95 patient (41.9%), 7 patients (3.1%), 10 patients (4.4%) and 23 patients (10.1%) respectively, and there was no HRAS mutation in all patients. RCC was 68 patients and LCRC was 159 patients. Poorly differentiated adenocarcinoma and mutinous adenocarcinoma were significantly more frequent in RCC compared to LCRC (P = 0.031). KRAS mutations were detected in 37 patients with RCC (54.4%) and in 58 patients with LCRC (36.5%). BRAF mutations were detected in 7 patient with RCC (10.3%) and in 3 patients with LCRC (1.9%). KRAS and BRAF mutation in RCC were significantly more frequent than in LCRC (P = 0.012 and P = 0.005, respectively). The incidence of NRAS and PIK3CA mutation was no difference between two groups. In all patients, overall survival was evaluated. On univariate Cox regression analysis, BRAF mutation was associated with significantly poorer overall survival than BRAF wild type (HR = 4.831, P = 0.013). Other oncogenic mutation status and tumor location weren’t associated with overall survival. Conclusions: KRAS and BRAF mutation were more frequent in the patients with RCC compared to those with LCRC in all stages. This study suggested BRAF mutation correlated with poor outcomes in patients with colorectal cancer.

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Survival Prediction in Patients With Glioblastoma Multiforme by Human Telomerase Genetic Variation

Journal of Clinical Oncology ◽

10.1200/jco.2005.04.0402 ◽

2006 ◽

Vol 24 (10) ◽

pp. 1627-1632 ◽

Cited By ~ 51

Author(s):

Luo Wang ◽

Qingyi Wei ◽

Li-E Wang ◽

Kenneth D. Aldape ◽

Yumei Cao ◽

...

Keyword(s):

Overall Survival ◽

Glioblastoma Multiforme ◽

Cox Regression ◽

Rank Test ◽

Survival Prediction ◽

Cox Regression Analysis ◽

Potential Biomarker ◽

Variant Genotype ◽

S Allele ◽

Human Telomerase

Purpose Glioblastoma multiforme (GBM) is the most common and aggressive glioma with the poorest survival. Use of biomarkers for screening patients with GBM may be used to modify treatments and improve outcomes. The level of human telomerase (hTERT) expression is an independent predictor of outcome of many cancers, and a functional variant of hTERT MNS16A (shorter tandem repeats or short [S] allele) is associated with increased hTERT mRNA expression. We investigated whether hTERT MNS16A variant genotype predicted survival in GBM patients. Patients and Methods We genotyped hTERT MNS16A in 299 GBM patients using polymerase chain reaction and determined hTERT genotype by classifying the DNA band of 243 or 272 base pairs (bp) as S allele and 302 or 333 bp as long (L) allele. We compared overall survival using Kaplan-Meier estimates and equality of survival distributions using the log-rank test, and we computed univariate and multivariate Cox proportional hazards models to estimate the effects of selected variables. Results Overall survival differed significantly by hTERT MNS16A genotype, with median survivals of 25.1, 14.7, and 14.6 months for the SS, SL, and LL genotypes, respectively. Compared with the SS genotype, the hazard ratios for the SL and LL genotypes were 1.69 and 1.87, respectively, after adjustment for other factors. Multivariate Cox regression analysis showed an independent statistically significant association between the hTERT MNS16A variant genotype and outcome. Conclusion A functional hTERT MNS16A genotype is a potential biomarker for assessment of survival outcome of GBM. Larger studies are needed to verify these findings.

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A Four−Gene-Based Risk Score With High Prognostic Value in Gastric Cancer

Frontiers in Oncology ◽

10.3389/fonc.2021.584213 ◽

2021 ◽

Vol 11 ◽

Author(s):

Bingdong Zhang ◽

Yuerui Li ◽

Liu Yang ◽

Yongbing Chen

Keyword(s):

Overall Survival ◽

Gastric Adenocarcinoma ◽

Risk Score ◽

Prognostic Value ◽

Cox Regression ◽

Prognostic Significance ◽

The Cancer Genome Atlas ◽

Risk Scores ◽

Mutation Status ◽

Risk Formula

BackgroundGastric adenocarcinoma is an important contributor to cancer mortality and morbidity. This study aimed to explore the prognostic value of mutation patterns in gastric adenocarcinoma.Materials and MethodsWe extracted somatic mutation data for 437 gastric adenocarcinoma samples from The Cancer Genome Atlas (TCGA) Stomach Adenocarcinoma (STAD) cohort. Kaplan–Meier survival in the R package maftools was used to analyze associations between mutations and survival. Multivariate Cox proportional model was used to establish risk formula. A four-gene-based risk score was developed to predict the overall survival of patients with gastric adenocarcinoma. We used the Tianjin cohort dataset with survival information to further evaluate the clinical value of this mutation signature.ResultsForty-five survival-related mutated genes were identified and verified, most of which were co-occurring in their mutation pattern and co-occurring with MLH3 and polymerase ϵ (POLE) mutations. Gastric adenocarcinoma samples with the 45 mutated genes had a significantly higher mutation count. Four-gene [UTRN, MUC16, coiled-coil domain-containing protein 178 (CCDC178), and HYDIN] mutation status was used to build a prognostic risk score that could be translated into the clinical setting. The association between the four-gene-based signature and overall survival remained statistically significant after controlling for age, sex, TNM stage, and POLE mutation status in the multivariate model [hazard ratio (HR), 1.88; 95% CI, 1.33–2.7; p < 0.001]. The prognostic significance of the four-gene-based risk score identified in TCGA cohort was validated in the Tianjin cohort.ConclusionA four-mutated gene risk formula was developed that correlated with the overall survival of patients with gastric adenocarcinoma using a multivariable Cox regression model. In two independent genomic datasets from TCGA and Tianjin cohorts, low risk scores were associated with higher tumor mutation loads and improved outcome in patients with gastric adenocarcinoma. This finding may have implications for prognostic prediction and therapeutic guidance for gastric adenocarcinoma.

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CES2 Expression in Pancreatic Adenocarcinoma Is Predictive of Response to Irinotecan and Is Associated With Type 2 Diabetes

JCO Precision Oncology ◽

10.1200/po.19.00330 ◽

2020 ◽

pp. 426-436

Author(s):

Michela Capello ◽

Johannes F. Fahrmann ◽

Mayrim V. Rios Perez ◽

Jody V. Vykoukal ◽

Ehsan Irajizad ◽

...

Keyword(s):

Type 2 Diabetes ◽

Overall Survival ◽

Cox Regression ◽

Ductal Adenocarcinoma ◽

Saline Control ◽

Serine Hydrolase ◽

Meaningful Improvement ◽

History Of ◽

Hba1c Levels

PURPOSE The combination chemotherapy of fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) has provided clinically meaningful improvement for pancreatic ductal adenocarcinoma (PDAC). We previously uncovered a role for the serine hydrolase carboxylesterase 2 (CES2) in mediating intratumoral activation of the prodrug irinotecan, a constituent of FOLFIRINOX. We aimed to further test the predictive value of CES2 for response to irinotecan using patient-derived xenograft (PDX) models and to elucidate the determinants of CES2 expression and response to FOLFIRINOX treatment among patients with PDAC. METHODS PDXs were engrafted subcutaneously into nude mice and treated for 4 weeks with either saline control or irinotecan. CES2 and hepatocyte nuclear factor 4 alpha (HNF4A) expression in PDAC tissues was evaluated by immunohistochemical and Western blot analysis. Kaplan-Meier and Cox regression analyses were applied to assess the association between overall survival and hemoglobin A1C (HbA1C) levels in patients who underwent neoadjuvant FOLFIRINOX treatment. RESULTS High CES2 activity in PDAC PDXs was associated with increased sensitivity to irinotecan. Integrated gene expression, proteomic analyses, and in vitro genetic experiments revealed that nuclear receptor HNF4A, which is upregulated in diabetes, is the upstream transcriptional regulator of CES2 expression. Elevated CES2 protein expression in PDAC tissues was positively associated with a history of type 2 diabetes (odds ratio, 4.84; P = .02). High HbA1C levels were associated with longer overall survival in patients who received neoadjuvant FOLFIRINOX treatment ( P = .04). CONCLUSION To our knowledge, we provide, for the first time, evidence that CES2 expression is associated with a history of type 2 diabetes in PDAC and that elevated HbA1C, by predicting tumor CES2 expression, may represent a novel marker for stratifying patients most likely to respond to FOLFIRINOX therapy.

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Albumin Is a Prognostic Factor for Response and Overall Survival in Relapsed or Refractory Acute Myeloid Leukemia (AML).

Blood ◽

10.1182/blood.v114.22.4685.4685 ◽

2009 ◽

Vol 114 (22) ◽

pp. 4685-4685

Author(s):

Rami S. Komrokji ◽

Mohamed A Kharfan-Dabaja ◽

Samantha L Price ◽

Gene A Wetzstein ◽

Alan F List ◽

...

Keyword(s):

Overall Survival ◽

Serum Albumin ◽

Prognostic Value ◽

Serum Albumin Level ◽

Cox Regression ◽

Salvage Chemotherapy ◽

Albumin Level ◽

Baseline Serum ◽

Kaplan Meier ◽

History Of

Abstract Abstract 4685 Background Hypoalbuminemia (HA) is a strong predictor of poor clinical outcomes in many medical conditions. Low serum albumin levels has been shown to be an adverse prognostic factor in patients with neoplastic diseases such as multiple myeloma, melanoma, and colon cancer. Severe hypoalbuminemia (<3.0 g/dl) at day +90 post allogeneic hematopoietic cell transplant (AHCT) was recently reported as an independent predictive variable for non-relapse mortality and overall survival (Kharfan-Dabaja, et al Biol Blood Marrow Transplant 2009;15). In this retrospective analysis we examined the prognostic value of serum albumin level at baseline, day 14 and day 30 of treatment with salvage chemotherapy regimens for relapsed or refractory AML (RR-AML). Methods Data were collected retrospectively in a cohort of patients with RR-AML patients who received CLAG (cladribine, cytarabine, and filgrastim) or MEC (mitoxantrone, etoposide, and cytarabine) regimens as salvage chemotherapy. The primary objective was to examine the relationship between serum albumin at baseline, day 14 and day 30 of salvage chemotherapy and probability for achieving complete remission (CR) and overall survival (OS). Patients were divided into two groups; the first group with serum albumin < 3.5 g/dl and the second group patients with serum albumin ≥3.5 g/dl. International Working Group criteria were used to define CR. Primary refractory AML (PR-AML) in this study was defined as failure to achieve CR1 and less than 50% reduction in myeloblasts after first line of induction. All analyses were conducted using SPSS version 15.0. (SPSS Inc, Chicago, IL). The Kaplan–Meier method was used to estimate median overall survival; chi-square test was used for comparison of categorical variables and t-test for continuous variables. Log rank test was used to compare Kaplan–Meier survival estimates between two groups and Cox regression for multivariable analysis. Results Between January 2005 and June 2008, 162 patients were treated with CLAG or MEC for RR-AML. Patient baseline characteristics were similar between patients with baseline serum albumin < 3.5 g/dl (HA) and those with serum albumin ≥ 3.5 g/dl (no HA) with respect to sex, FAB subtype, salvage chemotherapy, prior therapy and cytogenetics. Patients with HA were older, mean age 57 years compared to 52 years in non HA group (p=0.039). More patients with HA had prior history of MDS (35.6% versus 19.2%) (p=0.021). Based on baseline serum albumin obtained prior to start of salvage chemotherapy for RR-AML; overall CR rates were HA, 23.8% (19/80) vs. no HA, 41.2% (28/68) (p= 0.033). Median OS was 4.3 months for HA group vs. 8.07 months for no HA, p=0.028. Serum albumin at day 14 of salvage chemotherapy also correlated with OS. The CR was 38.5% for no HA and 27.1% for HA (p=0.12), median OS was 10.0 mo for no HA group versus 4.8 month (p=0.046). Serum albumin at day 30 of salvage chemotherapy was significantly correlated with survival as well with a median OS for HA group was 6.7 month compared to 13.44 month for no HA group (p=0.008).(figure-1) CR was 58% in no HA and 38% in HA group (p=0.072). In a multivariable Cox regression analysis including age, history of MDS, CR rates and serum albumin level at day 30; only CR rates and serum albumin were independent predictors of OS. (Table-1) Conclusion In this retrospective analysis of a cohort of patients with RR-AML; we demonstrated that serum albumin < 3.5 g/dl prior to start of salvage chemotherapy, at day 14 and at day 30 correlated with lower CR rates and worse OS. Serum albumin is a surrogate marker of general health, co- morbidities, and performance status. The prognostic value of low serum albumin need to be examined in newly diagnosed AML patients in context of known other prognostic factors; and validated in a prospective fashion. Disclosures: No relevant conflicts of interest to declare.

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Tobacco use and race as copredictors of overall survival in patients with breast cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.26_suppl.20 ◽

2013 ◽

Vol 31 (26_suppl) ◽

pp. 20-20 ◽

Cited By ~ 1

Author(s):

Jeremy Clady Wells ◽

Thomas A. Samuel ◽

Kyana Morton ◽

Stephen W. Looney

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Tobacco Use ◽

Cox Regression ◽

Statistical Significance ◽

Age At Diagnosis ◽

Stage At Diagnosis ◽

Inclusion Criteria ◽

Cox Regression Analysis ◽

History Of

20 Background: Tobacco use (TOB) has been linked to the development of breast cancer (BCa), but limited data exists linking TOB with overall survival (OS) and the influence of race on this relationship. Our previous research has shown that African-American (AA) patients with BCa have worse OS compared with Caucasian (C) patients. This retrospective study examines the effect of TOB on OS in BCa patients at Georgia Regents University (GRU) and the effect of race in conjunction with TOB on OS. Methods: Data were obtained from the GRU Tumor Registry. Inclusion criteria were all female patients diagnosed with BC between 2002 and 2010. The estimated hazard ratio (HR) from Cox regression was used to measure the association between TOB and OS. Race, age at diagnosis, and stage at diagnosis were considered for inclusion as covariates. A stratified OS analysis was also performed dividing patients by race (C vs. AA). Results: Data were collected on 836 females who met inclusion criteria. TOB was categorized as "none" vs. "any" at time of BCa diagnosis The Cox regression analysis indicated a decreased OS for women with any tobacco use (unadjusted HR, 1.45; p = 0.024). Statistical significance was retained when this HR was adjusted for race (HR, 1.47; p = 0.021) and age at diagnosis (HR, 1.45; p = 0.024), but not for stage at diagnosis (HR, 1.21; p = 0.266). In the stratified analysis, the results for C patients were similar to those obtained in the complete sample (HR, 1.62; p = 0.044). Statistical significance was not retained for AA patients (HR 1.31; p = 0.244). We compared C tobacco users (n = 157) vs. AA tobacco users (n = 127) (HR, 1.10; p = 0.716) and C tobacco non-users (n = 291) vs. AA tobacco non-users (n = 261) (HR, 1.36; p= 0.156) and found no statistical significance. Conclusions: Our analysis shows that patients with history of TOB at BCa diagnosis have a 45% chance of decreased OS compared to non-TOB users. The negative impact of TOB is still noted when adjusted for race and age at diagnosis but not for stage at diagnosis. When stratifying by race, we found that any TOB is a significant risk factor among C patients but not among AA patients. We conclude that any history of TOB at BCa diagnosis is an important negative prognostic factor for OS, and this is particularly true in C patients.

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