Influence of pre-diagnosis statin use on survival among patients with pancreatic cancer.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 427-427 ◽  
Author(s):  
Brian Z Huang ◽  
Jonathan I Chang ◽  
Bechien U Wu

427 Background: Recent studies have suggested associations between statin use and enhanced survival among patients with pancreatic ductal adenocarcinoma (PDAC). We aimed to explore the impact of pre-diagnosis statin treatment on survival across different agents and exposure levels. Methods: We conducted a retrospective cohort study on 2,142 pancreatic cancer patients diagnosed from 2006-2014 in an integrated healthcare system. Patients were identified from an internal cancer registry and followed until censored at death, date of last contact, or end of study. We used electronic pharmacy records to abstract information on the type, length and dosage of all statin exposures in the year prior to diagnosis. The overall influence of statins as well as the individual effects of simvastatin, lovastatin, atorvastatin, pravastatin and rosuvastatin were assessed using Cox proportional hazards regression. All analyses were adjusted for age, race, stage, receipt of surgery, receipt of chemotherapy and Charlson comorbidity index. We further adjusted for cholesterol control to determine whether statins acted through a lipid-mediated pathway. Results: Overall statin use was associated with a 13% decrease in the risk of mortality (HR 0.87, CI 0.79-0.97). Specifically, those who had used statins for 9-12 months (HR 0.85, CI 0.75-0.95), received higher doses (40+ mg/day) (HR 0.86, CI 0.76-0.98) or were active users at diagnosis (HR 0.86, CI 0.78-0.96) all had better survival compared to non-statin users. When assessing the individual statins, we found similar improvements in survival only among simvastatin users. Further stratified analyses revealed that simvastatin decreased the risk of death by 26% in stage IV patients (HR 0.74, CI 0.64-0.85), but had no effect for stage I-III patients (pinteraction= 0.03). Cholesterol control did not impact any of the associations between statin use and survival. Conclusions: We found that pre-diagnosis statin use, specifically simvastatin, was associated with improved survival in pancreatic cancer patients.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e19268-e19268
Author(s):  
Mehrnoosh Pauls ◽  
Abdulaziz AlJassim AlShareef ◽  
Winson Y. Cheung ◽  
Rachel Anne Goodwin ◽  
Brandon M. Meyers ◽  
...  

e19268 Background: Prior studies have demonstrated that clonal cells that give rise to pancreatic peritoneal metastases (PM) are geographically and genetically distinct from clonal cells, giving rise to lung and liver metastases. The objective of this study was to assess if there is a distinct difference in prognosis and therapeutic response among patients with pancreatic cancer with (PM compared to the lung/liver. Methods: Using a retrospective cohort design, medical records from adult patients diagnosed with metastatic adenocarcinoma of the pancreas at five Canadian academic cancer centers (2014 - 2019) were reviewed. Prognostic variables including age, Charlson comorbidity index, ECOG, cigarette smoking, nodal status, sites of metastases, and first line chemotherapy were collected. Cox proportional hazards model (MVA) was used to examine the association between peritoneal involvement and survival, adjusted for measured confounders. Analyses were completed using SAS, where alpha of 0.05 was defined as the level of significance. Results: A total of 1161 patients were included. Metastatic sites included peritoneum (n = 170, 14.6%), lung (n = 145, 12.5%) and liver (n = 563, 48.5%). Patients with PM received first-line FOLFIRINOX (FFX, n = 31), Gemcitabine + nab-paclitaxel (G/N, n = 20), Gemcitabine (G, n = 18), and no treatment (n = 97). In univariate analyses, worse ECOG PS was associated with PM (p = 0.002). The majority of patients died (89%), with a median overall survival (OS) of 3 vs 7 months for patients with PM and those without PM (p < 0.001), respectively. The median OS in patient whom receive first-line chemotherapy was 7 months in FFX group (95% CI 1.66-12.33), 6 months in G/N (95% CI 4.54-7.45) and 2 months in G group (95% CI 1.42-2.57). Patients had significantly better OS when treated with FFX or G/N compared to G alone (p = 0.002). Time to treatment failure was significantly shorter among patient treated with G alone compare to patients treated with FFX and G/N (P < 0.005). Conclusions: In the setting of combination chemotherapy for advanced pancreatic cancer, patients with PM continue to have a poor prognosis. This may be due to the impact of PM on PS and the inability to administer palliative chemotherapy. For eligible patients, FFX or G/N results in a higher OS than G monotherapy.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4522-4522 ◽  
Author(s):  
A. C. Berger ◽  
K. Winter ◽  
J. Hoffman ◽  
W. Regine ◽  
R. Abrams ◽  
...  

4522 Background: CA 19–9 is an important tumor marker in pancreatic adenocarcinoma. Several single institutional studies have demonstrated post-resection CA 19–9 to be an important prognostic factor. A secondary endpoint of RTOG 9704, a phase III adjuvant chemoradiation trial for pancreatic cancer, was to prospectively evaluate the ability of post-resectional CA 19–9 to predict survival. Methods: A total of 538 patients were accrued to this trial, of which 385 had evaluable CA 19–9 levels. These were analyzed using ELISA GI-MA kits provided by Diagnostic Products Corporation, a Siemens Company. CA 19–9 expression was analyzed as a dichotomized variable (<180 vs. =180). Cox proportional hazards models were utilized to characterize the contribution of CA 19–9 expression on OS. The following additional variables were included in the multivariate analysis: treatment, nodal involvement, tumor diameter (< or > 3cm), and margin status. Actuarial estimates for OS were calculated using Kaplan-Meier methods. Results: Most patients had CA 19–9 < 180 (n=220, 57%), while 34% were Lewis Antigen negative (unable to express CA 19–9) and 33 (9%) patients had levels >180. Survival was statistically significantly improved among patients with CA 19–9 <180 compared with those whose CA 19–9 =180 (HR=3.58(95% CI=2.40–5.34), p<0.0001) ( table ). This corresponds to a 72% reduction in the risk of death. This improvement was observed among patients with pancreas head and non-head tumors when analyzed separately. The multivariate analysis confirms that CA 19–9 is a highly significant predictor of OS in patients with resected pancreatic cancer. Conclusions: This prospective analysis of CA 19–9 in 385 patients treated with adjuvant chemoradiation definitively confirms the importance of post-resectional CA 19–9 in pancreatic cancer patients who have undergone resection. Patients with post-resection CA 19–9 >180 should be considered for additional therapy. [Table: see text] No significant financial relationships to disclose.


2020 ◽  
Author(s):  
Payam Peymani ◽  
Tania Dehesh ◽  
Farnaz Aligolighasemabadi ◽  
Mohammadamin Sadeghdoust ◽  
Katarzyna Kotfis ◽  
...  

Abstract Background: The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has profoundly affected the lives of millions of people. To date, there is no approved vaccine or specific drug to prevent or treat COVID-19, while the infection is spreading at an alarming rate globally. Because the development of effective vaccines or novel drugs could take several months (if not years), repurposing existing drugs is considered a more efficient strategy that could save lives now. Statins constitute a class of lipid-lowering drugs with proven safety profiles and many known beneficial pleiotropic effects. Our previous investigations showed that statins have antiviral effects and are involved in the process of wound healing in the lung. This triggered us to evaluate if statin use reduces mortality in COVID-19 patients. Results: After initial recruitment of 459 patients with COVID-19 (Shiraz province, Iran) and careful consideration of the exclusion criteria, a total of 150 patients, of which 75 received statins, were included in our retrospective study. Cox proportional-hazards regression models were used to estimate the association between statin use and rate of death. After propensity score matching, we found that statin use appeared to be associated with a lower risk of morbidity [HR=0.85, 95% CI=(0.02, 3.93), P=0.762] and lower risk of death [(HR= 0.76; 95% CI=(0.16, 3.72), P=0.735)]; however, these associations did not reach statistical significance. Furthermore, statin use reduced the chance of being subjected to mechanical ventilation [OR=0.96, 95% CI=(0.61–2.99), P=0.942] and patients on statins had a more normal computed tomography (CT) scan result [OR=0.41, 95% CI= (0.07–2.33), P=0.312]. Conclusions: Although we could not demonstrate a significant association between statin use and a reduction in mortality in patients with COVID19 , we do feel that our results are promising and of clinical relevance and warrant the need for prospective randomized controlled trials and extensive retrospective studies to validate the potential beneficial effects of statin treatment on clinical symptoms and mortality rates associated with COVID-19.


2019 ◽  
Vol 17 (3) ◽  
pp. 211-219 ◽  
Author(s):  
Nikolai A. Podoltsev ◽  
Mengxin Zhu ◽  
Amer M. Zeidan ◽  
Rong Wang ◽  
Xiaoyi Wang ◽  
...  

ABSTRACTBackground: Current guidelines recommend hydroxyurea (HU) as frontline therapy for patients with high-risk essential thrombocythemia (ET) to prevent thrombosis. However, little is known about the impact of HU on thrombosis or survival among these patients in the real-world setting. Patients and Methods: A retrospective cohort study was conducted of older adults (aged ≥66 years) diagnosed with ET from 2007 through 2013 using the linked SEER-Medicare database. Multivariable Cox proportional hazards regression models were used to assess the effect of HU on overall survival, and multivariable competing risk models were used to assess the effect of HU on the occurrence of thrombotic events. Results: Of 1,010 patients, 745 (73.8%) received HU. Treatment with HU was associated with a significantly lower risk of death (hazard ratio [HR], 0.52; 95% CI, 0.43–0.64; P<.01). Every 10% increase in HU proportion of days covered was associated with a 12% decreased risk of death (HR, 0.88; 95% CI, 0.86–0.91; P<.01). Compared with nonusers, HU users also had a significantly lower risk of thrombotic events (HR, 0.51; 95% CI, 0.41–0.64; P<.01). Conclusions: Although underused in our study population, HU was associated with a reduced incidence of thrombotic events and improved overall survival in older patients with ET.


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.


2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 119-119
Author(s):  
Christopher Leigh Hallemeier ◽  
Jennifer Moughan ◽  
Michael G. Haddock ◽  
Arnold M. Herskovic ◽  
Bruce D. Minsky ◽  
...  

119 Background: Radiotherapy (RT) interruptions have a negative impact on outcomes in many epithelial malignancies treated with definitive RT. The purpose of this study was to analyze the impact of RT duration on outcomes in patients (pts) with esophageal cancer treated with definitive chemoradiotherapy (CRT). Methods: Pts treated with definitive CRT on RTOG trials 8501 and 9405 were included. Separate analyses were performed in pts receiving standard dose (SD-CRT; 50 Gy + 5FU + cisplatin) and high dose (HD-CRT; 64.8 Gy + 5FU + cisplatin) CRT. Local (LF) and regional (RF) failure were estimated by the cumulative incidence method. Disease-free (DFS) and overall (OS) survival were estimated by the Kaplan-Meier method. Univariate (UVA) and multivariate (MVA) Cox proportional hazards models were utilized to examine for correlation between RT duration (< vs. ≥ median) with LF, RF, DFS and OS. Results: In the SD-CRT cohort (n=235), 96 pts (41%) had ≥ 1 RT interruption for a median of 3 (IQR 1-6) days. The median RT duration was 39 (IQR 37-43) days. In UVA and MVA, RT duration was not associated with LF, RF, DFS, or OS. Estimated outcome rates are in the table. In the HD-CRT cohort (n=107), 64 pts (60%) had ≥ 1 RT interruption for a median of 3.5 (IQR 2-7.5) days. The median RT duration was 52 (IQR 50-57) days. In UVA, RT duration ≥ 52 days was associated with a 33% reduction in risk of DFS failure (HR=0.66, 95% CI [0.44-0.98], p=0.039) and a 29% reduction in risk of death (HR=0.71, 95% CI [0.48-1.06], p=0.09). When excluding the 25 pts with RT dose < 64.8 Gy, RT duration was not associated with DFS or OS. Conclusions: In pts with esophageal cancer receiving definitive SD-CRT, an association between RT duration and outcomes was not observed. In pts receiving HD-CRT, longer RT duration was associated with improved DFS, which may have been due to a significant number of deaths at RT dose < 64.8 Gy. Supported by NCI U10 grants CA21661, CA180868, CA180822, CA37422. Clinical trial information: NCT00002631. [Table: see text]


2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 386-386
Author(s):  
Namrata Vijayvergia ◽  
Jenny Y Seo ◽  
Karthik Devarajan ◽  
Crystal Shereen Denlinger ◽  
Steven J. Cohen ◽  
...  

386 Background: Older mPC pts are less likely to receive chemotherapy (Ctx) and receive fewer agents compared to younger pts, yet have similar overall survival (OS). Both obesity and malnutrition are linked with poorer outcomes in pancreatic cancer. We evaluated the effect of body mass index (BMI) and nutritional state on survival in < 65 y (GpA) and > 65 y (GpB) mPC pts. Methods: With IRB approval, we retrospectively analyzed charts of 579 mPC pts treated between 2000 and 2010. GpA and GpB were compared based on BMI alone (<19, 20-25 and >25) and also their nutritional status (poor: albumin <3 or weight loss>15% during disease course with any BMI; good: Alb>3.5 + Wt loss<15% + BMI >20; intermediate: all others). Log-rank tests and Cox proportional hazards models were used to analyze OS and Fisher’s exact test to compare categorical variables. Results: There were 299 pts in GpA (median age 57yr) and 280 pts in GpB (median age 73 yr). Information on BMI/albumin was missing for 126 pts; total study population was 454 (GpA 238, GpB 216).Groups were well balanced for gender (majority male), PS (majority ≤1), initial stage (majority IV), and primary site (majority head). There was no significant difference in Ctx and number of agents used between the 3 subgroups across GpA and GpB. BMI alone did not affect survival in both groups. Nutritional status was significantly associated with survival when evaluating the whole population and GpA, but not GpB (Table). Good nutrition GpA pts had a lower relative risk of death versus pts in intermediate and poor nutrition groups (RR 0.83, CI 0.71-0.96, p=0.02). Good nutritional status was associated with better survival in GpA on multivariate analysis (RR=0.81, CI 0.69-0.95; p=0.008,), but not in GpB. Conclusions: Nutritional status (defined by BMI, albumin and weight loss) was associated with survival in younger mPC pts but not in older pts. Greater attention to nutrition and cancer cachexia with possible interventions throughout treatment may improve survival in mPC pts undergoing chemotherapy, especially those < 65 yrs. Table [Table: see text]


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16564-e16564
Author(s):  
Camille Ng ◽  
Sungjin Kim ◽  
Michelle Guan ◽  
Andrew Eugene Hendifar ◽  
Haesoo Kim ◽  
...  

e16564 Background: In rGC ( > cT2), we investigated the impact of various neoadjuvant and/or adjuvant treatment modalities on pathologic complete response (pCR), surgical margins, and overall survival (OS). Methods: The National Cancer Database (NCDB) was interrogated to identify rGC patients (pts) between 2004-2015. Gastric adenocarcinoma cases that were cT2-T4b, any N, M0 and underwent definitive surgery were included. We analyzed the association of 9 treatment groups: neoadjuvant chemoradiation only (nCRT), neoadjuvant chemo only (nCT), adjuvant chemo only (aCT), adjuvant chemoradiation only (aCRT), neoadjuvant chemo and adjuvant radiation (nCTaRT), received any chemo at all (any CT), received any chemoradiation at all (any CRT), received any radiation at all (any RT), and no perioperative therapy (NT) across 3 endpoints: pCR, margin status, and OS using logistic regression and Cox proportional hazards models with adjustment for baseline characteristics. Results: From 183,204 GC cases screened, a total 3061 pts were available with a median follow-up of 41.6 mos and median OS of 29.0 mos. On multivariable analyses, nCRT was associated with the greatest odds of having a pCR (odds ratio or OR 59.6, 95% confidence interval (CI) 10.6-334.1, p < 0.001) with NT as the reference. Having received any RT (OR 0.42, 0.10-1.86), nCRT (OR 0.68, 0.33-1.37), or nCT (OR 0.83, 0.60-1.15) was associated with the lowest odds for having positive surgical margins although none reached p < 0.05. For OS, having received any CT (hazard ratio or HR 0.41, 0.35-0.48) was associated with the lowest risk of death followed by nCRT (HR 0.48, 0.35-0.66), aCT (HR 0.52, 0.43-0.62), aCRT (HR 0.55, 0.48-0.63), any CRT (HR 0.61, 0.41-0.91), nCT (HR 0.62, 0.54-0.71), and nCTaRT (HR 0.67, 0.52-0.87, all p < 0.05). Median OS was greatest in pts treated with any CT (53.9 mos) followed by nCRT (39.1 mos) and aCT (36.1 mos) with 2-year OS rates being 65.6% (95% CI 61.3-69.5%), 63.6% (52.3-73.0%), and 59.7% (54.2-64.7%), respectively. Conclusions: Although nCRT had a high pCR rate, receipt of any CT (neoadjuvant and/or adjuvant) afforded the greatest OS in this modality-by-modality comparison in a large cohort of rGC pts.


2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Payam Peymani ◽  
Tania Dehesh ◽  
Farnaz Aligolighasemabadi ◽  
Mohammadamin Sadeghdoust ◽  
Katarzyna Kotfis ◽  
...  

Abstract Background The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has profoundly affected the lives of millions of people. To date, there is no approved vaccine or specific drug to prevent or treat COVID-19, while the infection is globally spreading at an alarming rate. Because the development of effective vaccines or novel drugs could take several months (if not years), repurposing existing drugs is considered a more efficient strategy that could save lives now. Statins constitute a class of lipid-lowering drugs with proven safety profiles and various known beneficial pleiotropic effects. Our previous investigations showed that statins have antiviral effects and are involved in the process of wound healing in the lung. This triggered us to evaluate if statin use reduces mortality in COVID-19 patients. Results After initial recruitment of 459 patients with COVID-19 (Shiraz province, Iran) and careful consideration of the exclusion criteria, a total of 150 patients, of which 75 received statins, were included in our retrospective study. Cox proportional-hazards regression models were used to estimate the association between statin use and rate of death. After propensity score matching, we found that statin use appeared to be associated with a lower risk of morbidity [HR = 0.85, 95% CI = (0.02, 3.93), P = 0.762] and lower risk of death [(HR = 0.76; 95% CI = (0.16, 3.72), P = 0.735)]; however, these associations did not reach statistical significance. Furthermore, statin use reduced the chance of being subjected to mechanical ventilation [OR = 0.96, 95% CI = (0.61–2.99), P = 0.942] and patients on statins showed a more normal computed tomography (CT) scan result [OR = 0.41, 95% CI = (0.07–2.33), P = 0.312]. Conclusions Although we could not demonstrate a significant association between statin use and a reduction in mortality in patients with COVID19, we do feel that our results are promising and of clinical relevance and warrant the need for prospective randomized controlled trials and extensive retrospective studies to further evaluate and validate the potential beneficial effects of statin treatment on clinical symptoms and mortality rates associated with COVID-19.


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.


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