scholarly journals Serum gamma-glutamyltransferase and the overall survival of metastatic pancreatic cancer

2019 ◽  
Author(s):  
Yuanyuan Xiao ◽  
Haijun Yang ◽  
Jian Lu ◽  
Dehui Li ◽  
Chuanzhi Xu ◽  
...  

Abstract Background: Accumulating evidence suggests that Gamma-glutamyltransferase (GGT) may be involved in cancer occurrence and progression. However, the prognostic role of serum GGT in pancreatic cancer (PC) survival lacks adequate evaluation. In this study, we aimed to analyze the association between serum GGT measured at diagnosis and overall survival (OS) in patients with metastatic PC. Methods: We identified 320 patients with histopathologically confirmed metastatic pancreatic ductal adenocarcinoma (PDAC) diagnosed during 2015 and 2016 at a specialized cancer hospital in southwestern China. Univariate and multivariate Cox proportional-hazards models were used to determine associations between serum GGT and OS in metastatic PDAC. Results: Controlled for possible confounding factors, serum GGT was significantly associated with OS: serum GGT >48 U/L yielded a hazard ratio of 1.53 (95%CI: 1.19-1.97) for mortality risk. A significant dose-response association between serum GGT and OS was also observed. Subgroup analysis showed a possible interaction between GGT and blood glucose level. Conclusion: Serum GGT could be a potential indicator of survival in metastatic PDAC patients. Underlying mechanisms for this association should be investigated.

2019 ◽  
Author(s):  
Yuanyuan Xiao ◽  
Haijun Yang ◽  
Jian Lu ◽  
Dehui Li ◽  
Chuanzhi Xu ◽  
...  

Abstract Background: Accumulating evidence suggests that Gamma-glutamyltransferase (GGT) may be involved in cancer occurrence and progression. However, the prognostic role of serum GGT in pancreatic cancer (PC) survival lacks adequate evaluation. In this study, we aimed to analyze the association between serum GGT measured at diagnosis and overall survival (OS) in patients with metastatic PC. Methods: We identified 320 patients with histopathologically confirmed metastatic pancreatic ductal adenocarcinoma (PDAC) diagnosed during 2015 and 2016 at a specialized cancer hospital in southwestern China. Univariate and multivariate Cox proportional-hazards models were used to determine associations between serum GGT and OS in metastatic PDAC. Results: Controlled for possible confounding factors, serum GGT was significantly associated with OS: serum GGT >48 U/L yielded a hazard ratio of 1.53 (95%CI: 1.19-1.97) for mortality risk. A significant dose-response association between serum GGT and OS was also observed. Subgroup analysis showed a possible interaction between GGT and blood glucose level. Conclusion: Serum GGT could be a potential indicator of survival in metastatic PDAC patients. Underlying mechanisms for this association should be investigated.


BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Yuanyuan Xiao ◽  
Haijun Yang ◽  
Jian Lu ◽  
Dehui Li ◽  
Chuanzhi Xu ◽  
...  

Abstract Background Accumulating evidence suggests that Gamma-glutamyltransferase (GGT) may be involved in cancer occurrence and progression. However, the prognostic role of serum GGT in pancreatic cancer (PC) survival lacks adequate evaluation. In this study, we aimed to analyze the association between serum GGT measured at diagnosis and overall survival (OS) in patients with metastatic PC. Methods We identified 320 patients with histopathologically confirmed metastatic pancreatic ductal adenocarcinoma (PDAC) diagnosed during 2015 and 2016 at a specialized cancer hospital in southwestern China. Univariate and multivariate Cox proportional-hazards models were used to determine associations between serum GGT and OS in metastatic PDAC. Results Controlled for possible confounding factors, serum GGT was significantly associated with OS: serum GGT > 48 U/L yielded a hazard ratio of 1.53 (95% CI: 1.19–1.97) for mortality risk. A significant dose-response association between serum GGT and OS was also observed. Subgroup analysis showed a possible interaction between GGT and blood glucose level. Conclusion Serum GGT could be a potential indicator of survival in metastatic PDAC patients. Underlying mechanisms for this association should be investigated.


2019 ◽  
Author(s):  
Yuanyuan Xiao ◽  
Haijun Yang ◽  
Jian Lu ◽  
Dehui Li ◽  
Chuanzhi Xu ◽  
...  

Abstract Background Accumulating evidence suggests that Gamma-glutamyltransferase (GGT) may be involved in cancer occurrence and progression. However, a prognostic role of serum GGT in pancreatic cancer (PC) survival lacks adequate evaluation. In this study, we aimed to analyze the association between serum GGT measured at diagnosis and overall survival (OS) in patients with metastatic PC. Methods We identified 320 patients with histopathologically confirmed metastatic pancreatic ductal adenocarcinoma (PDAC) diagnosed during 2015 and 2016 at a specialized cancer hospital in southwest China. Univariate and multivariate Cox proportional hazards models were used to determine associations between serum GGT and OS in metastatic PDAC. Results Under control for possible confounding factors, serum GGT was significantly associated with OS: serum GGT >48 U/L yielded a hazard ratio of 1.53 (95%CI: 1.19-1.97) for mortality risk. Significant dose-response between serum GGT and OS was also observed. Subgroup analysis showed some evidence for an interaction between GGT and blood glucose level. Conclusion Serum GGT could be a promising indicator of survival in metastatic PDAC patients. Underlying mechanisms for this association should be investigated.


2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 421-421
Author(s):  
Mariam F. Eskander ◽  
Gyulnara G. Kasumova ◽  
Chun Li ◽  
Sing Chau Ng ◽  
Rebecca A. Miksad ◽  
...  

421 Background: There are increasing therapeutic options for patients with advanced pancreatic cancer but it is unknown whether the overall prognosis of unresectable patients is improving. Here, we examine trends in treatment and survival in Stage III/IV pancreatic cancer. Methods: National Cancer DataBase 1998-2012 queried for unresected pancreatic adenocarcinoma patients from Commission on Cancer hospitals with Stage III and IV disease. Trends in stage at diagnosis and type of chemotherapy (single vs. multi-agent) assessed via Cochran Armitage trend tests. Timing of treatment compared by Kruskal-Wallis. Kaplan-Meier analysis and Cox proportional hazards models used to assess the association between 2-year time intervals (1998-2011) and survival. Results: 34,163 unresected patients with Stage III and 100,396 with stage IV identified. Rates of chemotherapy increased over time for stage III (p<0.0001) and stage IV (p<0.0001). Among patients who received systemic therapy, rates of multiagent chemotherapy have increased for both stage III (p<0.0001) and IV (p<0.0001). Time from diagnosis to treatment did not change (p=0.5121). Overall survival differed by year group for stage III (5.2 mos in 1998-1999 vs. 9.0 mos 2010-2011, log-rank p<0.0001) and stage IV (3.1 vs. 3.6 mos; log-rank p<0.0001). Among patients who received chemotherapy, overall survival also differed (Stage III, 7.6 vs. 11.4 mos, log-rank p<0.0001; Stage IV, 5.0 vs. 6.0 mos, log-rank p<0.0001). After stratification by clinical stage, type of chemotherapy, tumor location, and facility type, year remained a significant predictor of survival (p<0.0001). Conclusions: Survival of patients with Stage III and IV pancreatic cancer has significantly improved over the last fifteen years. This improvement in survival is not fully explained by changes in chemotherapy. [Table: see text]


2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 216-216 ◽  
Author(s):  
Jaewon Park ◽  
In Kuk Cho ◽  
Jong-Chan Lee ◽  
Jongchan Lee ◽  
Young Hoon Kim ◽  
...  

216 Background: Pancreatic protocol CT (pCT) is widely used to evaluate stage and resectability of pancreatic ductal adenocarcinoma (PDAC). Recent studies show that CT enhancement patterns are related to the patient’s prognosis in several cancers, however it is not well described that pCT enhancement has prognostic effect in resectable PDAC so far. We aimed to show correlaton between pCT enhancements and prognosis in resectable PDAC. Methods: We retrospectively enrolled 159 patients (median age, 67.8 years) who underwent pCT before curative resection in Seoul National University Bundang Hospital between January 2010 and December 2015, with final pathological diagnosis of PDAC. CT enhancement ratio (CTER) of each primary lesion was calculated as proportional difference between maximum Houndsfield Unit (HU) of pancreatic phase (PP) image and maximum HU of non-contrast image; [(max HU of PP) - (max HU of non-contrast)] / (max HU of non-contrast). Patients were classified into two groups, based on CTER. Kaplan–Meier analysis and Cox proportional hazards models were used to correlate CTER with overall survival (OS) and recurrence free survival (RFS). Results: Median overall survival was 22.0 months during a median follow-up period of 18.5 months. Based on CTER with cut-off value of 1.8, higher (CTER ≥ 1.8) group (N = 43) was compared with lower (CTER < 1.8) group (N = 116) in terms of OS and RFS. Lower group showed significantly shorter median OS (18.5 months versus 39.3 months, P < 0.001) and median RFS (9.9 months versus 21.5 months, P = 0.006) than those of higher group. Multivariate regression analysis showed that lower group had shorter OS (HR 1.70; CI 1.01-2.85, P = 0.044) and RFS (HR 1.84; CI 1.10-3.06, P = 0.019). Conclusions: Our study suggests that lower enhancement in pancreatic phase of pCT is related to poor prognosis in PDAC. Therefore, active surveillance would be required in resected PDAC patients with CTER less than 1.8.


2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 240-240
Author(s):  
Sina Vatandoust ◽  
Ganessan Kichenadasse ◽  
Michael E O'Callaghan ◽  
Tina Kopsaftis ◽  
Scott Walsh ◽  
...  

240 Background: In 15-30% of pts with metastatic PCa who progress on Maximal Androgen Blockade (MAB), withdrawal of the antiandrogen agent (AAWD) and continuing the LHRH agonist alone, leads to PSA decreases of ≥50% and prolonged progression free survival. Here we describe patient and disease characteristics, treatment history and outcomes of pts who have been managed with AAWD. Methods: Data were obtained from SA-PCCOC (a longitudinal, observational registry of biopsy-proven PCa cases, throughout the Australian state of South Australia since 1998). Proportions were compared using a Chi squared test. A multivariable model used competing risks (Fine and Gray) and Cox proportional Hazards models to assess overall survival and Prostate cancer specific mortality (PCSM). Survival was calculated from the date of rising PSA for patients on LHRH and AA. Results: 140 pts were found to have MAB. Of these, 31(22.1%) had AAWD. In the AAWD group, median age was 81y (51-95). Age at diagnosis, Gleason score at biopsy and diagnostic PSA were not significantly different amongst the two groups. Treatment PSA was significantly lower in the AAWD group (20.55 (range 0.6-9,995) vs 50.50 (range 0.95-4378) p= 0.02). There was a significant association of AAWD with PCSM (sHR 0.35, 95% CI 0.16-0.76; p = 0.008). Also significant in the model was prior time on hormones (sHR [per month increase] 0.96 95% CI 0.95-0.98, p<0.001). There was also a significant association of AAWD with overall survival (HR 0.22, 95% CI 0.10-0.46; p <0.001). Again, prior time on hormones was also significant (HR [per month increase] 0.96 95% CI 0.95-0.98, p<0.001). Multivariate analysis was performed on data from 80 pts (60 pts omitted due to missing data). Conclusions: Pts in whom AAWD was used were older and had lower treatment PSA. In this small cohort, AAWD was associated with both reduced PCSM and overall risk of death. The time spent on MAB also appeared to be significant. This retrospective observational study may be subject to confounding, however the observation warrants further investigation in larger cohorts and in a prospective setting.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16659-e16659
Author(s):  
Sunyoung S. Lee ◽  
Yehia I. Mohamed ◽  
Aliya Qayyum ◽  
Manal Hassan ◽  
Lianchun Xiao ◽  
...  

e16659 Background: Child-Turcotte-Pugh (CTP) score is widely used in the assessment of prognosis of HCC and CTP-A is the standard criterion for active therapy and clinical trials entry. Recently, ALBI and insulin-like growth factor-1 (IGF)-CTP scores have been reported to improve survival prediction over CTP score. However, comparative studies to compare both scores and to integrate IGF into Albi score are lacking. Methods: After institutional board approval, data and samples were prospectively collected. 299 HCC patients who had data to generate both IGF-CPG and Albi index were used. The ALBI index, and IGF score were calculated, Cox proportional hazards models were fitted to evaluation the association between overall survival (OS) and CTP, IGF-CTP, Albi and IGF, albumin, bilirubin. Harrell’s Concordance index (C-index) was calculated to evaluate the ability of the three score system to predict overall survival. And the U-statistics was used to compare the performance of prediction of OS between the score system. Results: OS association with CTP, IGF-CTP and Albi was performed (Table). IGF-CTP B was associated with a higher risk of death than A (HR = 1.6087, 95% CI: 1.2039, 2.1497, p = 0.0013), ALBI grade 2 was also associated with a higher risk of death than 1 (HR = 2.2817, 95% CI: 1.7255, 3.0172, p < 0.0001). IGF-1(analyzed as categorical variable) was independently associated with OS after adjusting for the effects of ALBI grade. Which showed IGF-1 ≤26 was significantly associated with poor OS, P = 0.001. Conclusions: Although ALBI grade and IGF-CTP score in this analysis had similar prognostic values in most cases, their benefits might be heterogenous in some specific conditions. We looked into corporation of IGF-1 into ALBI grade, IGF score with cutoff ≤26 which clearly refined OS prediction and better OS stratification of ALBI-grade.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e18002-e18002
Author(s):  
Bernard Tawfik ◽  
Sarunas Sliesoraitis ◽  
Heidi D. Klepin ◽  
Julia Lawrence ◽  
Scott Isom ◽  
...  

e18002 Background: The hypomethylating agents, azacitidine and decitabine, have emerged as an alternative to initial and salvage therapy in patients with AML. Little is known about how AML responds to hypomethylating agents after standard therapy and the use of these agents in the treatment of AML is currently evolving. Methods: We retrospectively examined 76 consecutive AML patients ≥60 years old treated with hypomethylating agents at Wake Forest from 2002-2009 as either 1st-line therapy (n=35), salvage (n=28) or consolidation (n=13). We collected data on age, gender, race, Charleston Comorbidity index (CCI), cytogenetics, type of treatment, Complete Remission (CR), Complete Remission with incomplete count recovery (CRi), and survival. Statistical analysis was performed using Kaplan-Meier estimates and cox proportional hazards models. Results: In the front line setting 11.4% of patients received azacitidine (AZA), 34.3% received 5 days of decitabine (5DD) and 54.3% received 10 days (10DD). In the salvage cohort 3.6% received AZA, 42.8% received 5DD and 53.6% received 10DD. In the consolidation cohort 18.2% received AZA and 81.8% received 5DD. Response rates (CR+CRi) were reduced in the salvage cohort compared to frontline (3.6% versus 25.7%, p=0.033). Despite the reduced response rate, overall survival in the two cohorts was similar when survival was calculated from time of hypomethylating agent (8.2 [CI 4.8-10.3] vs. 3.1 [CI 1.9-12.0] months, p = 0.2967). In the salvage cohort overall survival from the time of relapse was similar to the overall survival of those treated in 1st consolidation (18.3 [CI 15.1 -23.5] vs. 13.7 [CI 8.0 – 21.6] months, p= 0.3346). This suggests that hypomethylating agents given in first remission did not improve survival over patients who received them only after relapse. Comorbidity burden (by the CCI) showed a non-significant trend with prognosis (p= 0.0667). Conclusions: These data suggest prior cytotoxic therapy decreases marrow response rates to hypomethylating agents but not survival. Furthermore, use of hypomethylating agents for consolidation did not result in an increase in median overall survival when compared to their use in salvage.


2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 487-487
Author(s):  
Julia Anne Batten ◽  
Wolfram E. Samlowski ◽  
Kinjal Parikh ◽  
Arun Sendilnathan ◽  
Hilda Crispin ◽  
...  

487 Background: HD IL-2 is associated with an objective response rate of 16-20% with durability of response in select mRCC patients. HD IL-2 is also associated with significant toxicity including vascular leak syndrome and inflammatory side effects. Few predictive markers can identify patients likely to respond to HD IL-2. Methods: Patients treated with HD IL-2 at the University of Utah Huntsman Cancer Institute from 2000 to 2012 with clear cell mRCC were evaluated. Grade of toxicities during HD IL-2 treatment were collected based on provider documentation in the electronic health record. Rates of adverse events (AEs) and overall survival stratified grade 3 AEs were evaluated by Kaplan-Meier survival estimates and Cox proportional hazards models. All AEs were graded per common terminology criteria version 4. Grade 3 rigors were defined as severe rigors requiring opioids. Results: A total of 85 patients were included with a median age of 56 years (range 32-76 years) and 79% (n = 67) were male. Patients belonged to the following MSKCC risk categories: 11 (13%) good, 70 (82%) intermediate, and 4 (5%) poor risk. The mean total dose received was 1097 MIU (range: 160 – 3048 MIU). The prevalence of grade 3 AEs is presented in the table. Median survival of patients with ≥grade 3 rigors after HD IL-2 administration was 1501 days vs 533 days for those without (p = 0.0005, HR 2.54). Presence of rigors was also associated with a significant improvement in progression free survival, time to next treatment and response rates. No other AEs predicted response to HD IL-2. Conclusions: Presence of grade 3 rigors predicts improved survival during HD IL-2 therapy. Notably, grade 3 fever was rarely observed because of our institutional protocol of routinely using scheduled antipyretics to diminish fevers. [Table: see text]


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15729-e15729
Author(s):  
Michael Shusterman ◽  
Erin Jou ◽  
Andreas Kaubisch ◽  
Jennifer W. Chuy ◽  
Lakshmi Rajdev ◽  
...  

e15729 Background: The neutrophil to lymphocyte ratio (NLR), a marker of systemic inflammatory response, has been suggested as a prognostic marker in patients with pancreatic adenocarcinoma (PAC). Black and Hispanic patients have been underrepresented in studies evaluating the significance of NLR in PAC. We investigated the prognostic significance of NLR in patients with advanced PAC treated at the Montefiore-Einstein Center for Cancer Care (MECCC) in the Bronx, NY. Methods: We included patients who were chemotherapy naive and treated for unresectable or metastatic PAC at MECCC between 2006 and 2015. Demographics, clinical characteristics and treatment data were collected. Overall survival was determined by the Kaplan-Meier method and Cox proportional-hazards models were built to assess survival differences adjusting for clinically relevant and statistically significant variables. Results: 201 patients were included in the study. Median age was 65 (range 32, 90). 52% were male. 41 were White (19%), 71 Black (33%), 71 Hispanic (33%), and 33 Other (15.3%). 66 (30.6%) had unresectable disease and 135 (62.5%) metastatic disease. An NLR ≥ 4 was associated with a worse OS compared to an NLR ≤ 4 (median 10 vs. 16.4 months; HR 1.895; 95% CI 1.390, 2.585; P < 0.0001). Predictors of worse OS on univariate analysis were ever smoker status (HR 1.365; P = 0.05), metastatic disease (HR 1.736; P = 0.001), and albumin ≤ 3.5 g/dL (HR 2.558; P< 0.0001). An NLR ≥ 4 on multivariate analysis remained significantly associated with worse OS (HR 1.665; 95% CI 1.188, 2.334; P = 0.003) after adjusting for age, gender, ever smoker status, metastatic disease, and albumin. Conclusions: In a cohort with significant minority patient representation, an NLR ≥ 4 was associated with significantly worse overall survival in patients with advanced pancreatic cancer. An elevated NLR in advanced PAC may be an important independent predictor to risk stratify patients and predict poor OS in future analyses.


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