Outcomes of Patients With Advanced Gastrointestinal Cancer in Relationship to Opioid Use: Findings From Eight Clinical Trials

Background: This study assessed the patterns of opioid use among patients with advanced gastrointestinal cancers who were included in 8 clinical trials and evaluated the impact of opioid use on survival outcomes of included patients. Methods: Deidentified datasets from 8 clinical trials evaluating first-line systemic treatment of advanced gastrointestinal cancers were accessed from the Project Data Sphere platform (ClinicalTrial.gov identifiers: NCT01124786, NCT00844649, NCT00290966, NCT00678535, NCT00699374, NCT00272051, NCT00305188, and NCT00384176). These trials evaluated patients with pancreatic carcinoma, gastric carcinoma, hepatocellular carcinoma (HCC), and colorectal carcinoma. Multivariable logistic regression analysis was used to evaluate factors predicting the use of opioids. Kaplan-Meier survival estimates were used to compare survival outcomes in each disease entity among patients who did or did not receive opioid treatment. Multivariable Cox regression analysis was then used to further assess the impact of opioid use on survival outcomes in each disease entity. Results: A total of 3,441 participants were included in the current analysis. The following factors predicted a higher probability of opioid use within logistic regression analysis: younger age at diagnosis (odds ratio [OR], 0.990; 95% CI, 0.984–0.997; P=.004), nonwhite race (OR for white vs nonwhite, 0.749; 95% CI, 0.600–0.933; P=.010), higher ECOG score (OR for 1 vs 0, 1.751; 95% CI, 1.490–2.058; P<.001), and pancreatic primary site (OR for colorectal vs pancreatic, 0.241; 95% CI, 0.198–0.295; P<.001). Use of opioids was consistently associated with worse overall survival (OS) in Kaplan-Meier survival estimates of each disease entity (P=.008 for pancreatic cancer; P<.001 for gastric cancer, HCC, and colorectal cancer). In multivariable Cox regression analysis, opioid use was associated with worse OS among patients with pancreatic cancer (hazard ratio [HR], 1.245; 95% CI, 1.063–1.459; P=.007), gastric cancer (HR, 1.725; 95% CI, 1.403–2.122; P<.001), HCC (HR, 1.841; 95% CI, 1.480–2.290; P<.001), and colorectal cancer (HR, 1.651; 95% CI, 1.380–1.975; P<.001). Conclusions: Study findings suggest that opioid use is consistently associated with worse OS among patients with different gastrointestinal cancers. Further studies are needed to understand the underlying mechanisms of this observation and its potential implications.

Download Full-text

Outcomes of advanced gastrointestinal (GI) cancer patients in relationship to opioid use: An individual patient data pooled analysis from eight clinical trials.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.4_suppl.687 ◽

2020 ◽

Vol 38 (4_suppl) ◽

pp. 687-687

Author(s):

Omar Abdel-Rahman ◽

Hatim Karachiwala ◽

Jacob C. Easaw

Keyword(s):

Overall Survival ◽

Clinical Trials ◽

Regression Analysis ◽

Cox Regression ◽

Survival Outcomes ◽

Disease Entity ◽

Opioid Use ◽

Cox Regression Analysis ◽

Gi Cancers ◽

The Impact

687 Background: The current study aims at assessing the patterns of opioid use, and evaluating the impact of opioid use on survival outcomes among patients with advanced GI cancers who were included in eight clinical trials. Methods: De-identified datasets of eight clinical trials evaluating first-line systemic treatment for advanced GI cancers (NCT01124786; NCT00844649; NCT00290966; NCT00678535; NCT00699374; NCT00272051; NCT00305188; NCT00384176) were accessed from the Project Data Sphere platform. These trials evaluated patients with pancreatic, gastric, hepatocellular and colorectal carcinoma. Multivariable logistic regression analysis was used to evaluate factors predicting the use of opioids. Kaplan-Meier survival estimates were used to compare survival outcomes in each disease entity among patients who did or did not receive opioid treatment. Multivariable Cox regression analysis was used to assess the impact of opioid use on survival outcomes in each disease entity. Results: A total of 3441 participants were included in the current analysis. The following factors predicted a higher probability of opioid use within logistic regression analysis: younger age (P = 0.004), non-white race (P = 0.010), higher ECOG score (P < 0.001) and pancreatic primary site (P < 0.001). Use of opioids was consistently associated with worse overall survival in Kaplan-Meier survival estimates of each disease entity (for pancreatic cancer: P = 0.008; for gastric cancer: P < 0.001; for hepatocellular carcinoma: P < 0.001 and for colorectal cancer: P < 0.001). Within multivariable Cox regression analysis, opioid use was associated with worse overall survival among patients with pancreatic cancer (HR = 1.245; 95% CI: 1.063-1.459; P = 0.007), gastric cancer (HR = 1.725; 95% CI: 1.403-2.122; P < 0.001), hepatocellular carcinoma (HR = 1.841; 95 CI: 1.480-2.290; P < 0.001) and colorectal cancer (HR = 1.651; 95% CI: 1.380-1.975; P < 0.001). Conclusions: Opioid use is consistently associated with worse overall survival among patients with different GI cancers. Further studies are needed to evaluate the underlying mechanisms of this observation.

Download Full-text

Cisplatin-Based versus Carboplatin-Based Chemotherapy for Extra-Pulmonary Neuroendocrine Carcinomas; A Real-World Study.

Neuroendocrinology ◽

10.1159/000520193 ◽

2021 ◽

Author(s):

Omar Abdel-Rahman ◽

Sheryl L. Koski

Keyword(s):

Overall Survival ◽

Regression Analysis ◽

Cox Regression ◽

Survival Outcomes ◽

Cox Regression Analysis ◽

Kaplan Meier ◽

Platinum Agent ◽

Extra Pulmonary ◽

The Impact ◽

Neuroendocrine Carcinomas

Objective: To assess the survival differences between cisplatin/etoposide versus carboplatin/etoposide chemotherapy regimens in the management of extra-pulmonary neuroendocrine carcinomas (NECs). Methods: Administrative cancer care databases in the province of Alberta, Canada were reviewed, and patients with extra-pulmonary NECs (including those with small cell and large cell neuroendocrine carcinomas) who were treated with either cisplatin/ etoposide or carboplatin/ etoposide, 2004-2019, were reviewed. Kaplan-Meier survival estimates were used to compare the survival outcomes according to the type of platinum agent, and multivariable Cox regression analysis was used to assess the impact of the type of platinum agent on overall survival outcomes. Results: A total of 263 eligible patients were included in this analysis. These include 176 patients who received cisplatin/ etoposide and 87 patients who received carboplatin/etoposide. Using Kaplan-Meier survival estimates, patients treated with cisplatin have better overall survival compared to patients treated with carboplatin (P=0.005). Multivariable Cox regression analysis suggested that the following factors were associated with worse overall survival: higher Charlson comorbidity index (HR: 1.17; 95% CI: 1.05-1.30), gastrointestinal primary site (HR: 1.55; 95% CI: 1.12-2.14), stage IV disease (HR: 1.75; 95% CI: 1.28-2.38) and use of carboplatin (HR: 1.40; 95% CI: 1.02-1.92). Conclusions: The current study suggested that cisplatin/etoposide might be associated with better overall survival compared to carboplatin/etoposide among patients with extra-pulmonary NECs. It is unclear if this is related to differences in inherent responsiveness to the two platinum agents, or due to differences in comorbidity burden between the two treatment groups.

Download Full-text

Impact of Body Mass Index on Survival Outcome in Patients with Newly Diagnosed Glioblastoma: A Retrospective Single-Center Study

Integrative Cancer Therapies ◽

10.1177/1534735421991233 ◽

2021 ◽

Vol 20 ◽

pp. 153473542199123

Author(s):

Jun-Yong Cha ◽

Jae-Sung Park ◽

Yong-Kil Hong ◽

Sin-Soo Jeun ◽

Stephen Ahn

Keyword(s):

Cox Regression ◽

Survival Outcomes ◽

Newly Diagnosed ◽

Eligibility Criteria ◽

Cox Regression Analysis ◽

Asian Populations ◽

Kaplan Meier ◽

Single Center Study ◽

Newly Diagnosed Glioblastoma ◽

The Impact

Introduction: The impact of obesity on survival outcomes in patients with glioblastoma (GBM) has not been well reported and the results for patients are currently unclear. We investigated the effect of obesity on survival outcomes in patients with newly diagnosed GBM. Methods: Using electronic medical records, all GBM patients that visited the Seoul St. Mary’s Hospital between 2008 and 2018 were reviewed. A total of 177 patients met our eligibility criteria. The cut-off point for BMI was 23.0 kg/m2 based on previous studies which focused on Asian populations. Results: A total of 177 patients met our eligibility criteria. The overall median BMI of patients was 24.5 kg/m2 (range 15.82-39.26). About 62 patients who had a BMI less than the cut-off value were assigned to the “lower BMI” group, while 115 patients who had a BMI greater than the cut-off value were assigned to the “higher BMI” group. In Kaplan-Meier survival analysis, the median OS of the higher BMI group was longer than that of the lower BMI group (21.3 months vs 15.3 months, P = .002). In multivariate Cox regression analysis for OS, lower BMI was associated with inferior OS (HR 1.48 CI 1.06-2.08, P = .002). Conclusion: Our findings suggest that elevated BMI may be associated with better survival in patients with newly diagnosed GBM. Additional larger prospective studies could help validate our findings to confirm the effect of body composition and survival outcomes in GBM patients.

Download Full-text

The Role of Chemotherapy in the Survival Benefits of Patients Aged Older Than 40 Years With Osteosarcoma

Technology in Cancer Research & Treatment ◽

10.1177/15330338211066195 ◽

2021 ◽

Vol 20 ◽

pp. 153303382110661

Author(s):

Zhiyou Cao ◽

Yuelin Zhang ◽

Qiang Xu ◽

Xiaolong Yu ◽

Xuqiang Liu ◽

...

Keyword(s):

Regression Analysis ◽

Survival Benefit ◽

Cox Regression ◽

Rank Test ◽

Cancer Specific Survival ◽

Cox Regression Analysis ◽

Kaplan Meier ◽

Stratified Analysis ◽

The Impact ◽

Grade Iii

Objectives: The value of chemotherapy in the survival benefits of patients aged > 40 years with osteosarcoma is controversial. We aimed to explore the impact of chemotherapy on the survival benefits of patients aged >40 years with osteosarcoma. Methods: The Surveillance, Epidemiology, and End Results database was used to select eligible patients. The selected patients were divided into the chemotherapy and non-chemotherapy groups. Logistic regression analysis was performed to investigate the potential factors contributing to the selection of chemotherapy. The overall survival (OS) and cancer-specific survival (CSS) of the two groups were compared using the Kaplan–Meier method with a log-rank test. Cox proportional risk models were used to determine the prognostic factors for OS and CSS. Stratified analysis was performed according to tumour grade and stage. Results: A total of 1032 eligible patients were included in our analysis. Of these, 586 and 446 patients were in the chemotherapy and nonchemotherapy groups, respectively. Multivariate logistic analysis indicated that grade III/IV and distant stage were associated with chemotherapy. Kaplan–Meier plots showed that patients did not achieve an improved OS or CSS after receiving chemotherapy. Cox regression analysis indicated that age > 60 years, axial, grade III/IV, and regional and distant stage were independent risk factors for poor prognosis in both OS and CSS. Stratified analysis revealed a survival benefit from chemotherapy in patients with grade III/IV and distant stage. Conclusions: Chemotherapy did not significantly improve OS and CSS in patients aged > 40 years with osteosarcoma. In this age group, survival benefit from chemotherapy was observed in patients with high-grade tumours (grade III/IV) and metastasis (distant stage).

Download Full-text

NLRP3 is a Novel Prognostic Biomarker and Correlates With Immune Infiltrates in Lung Adenocarcinoma and Skin Cutaneous Melanoma

10.21203/rs.3.rs-880002/v1 ◽

2021 ◽

Author(s):

Chenxi Yuan ◽

Qingwei Wang ◽

Xueting Dai ◽

Yipeng Song ◽

Jinming Yu

Keyword(s):

Logistic Regression ◽

Regression Analysis ◽

Lung Adenocarcinoma ◽

Immune Cells ◽

Cutaneous Melanoma ◽

Cox Regression ◽

Cox Regression Analysis ◽

Potential Biomarker ◽

The Impact ◽

Nlrp3 Expression

Abstract Background: Lung adenocarcinoma (LUAD) and skin cutaneous melanoma (SKCM) are common tumors around the world. However, the prognosis in advanced patients is poor. Because NLRP3 was not extensively studied in cancers, so that we aimed to identify the impact of NLRP3 on LUAD and SKCM through bioinformatics analyses. Methods: TCGA and TIMER database were utilized in this study. We compared the expression of NLRP3 in different cancers and evaluated its influence on survival of LUAD and SKCM patients. The correlations between clinical information and NLRP3 expression were analyzed using logistic regression. Clinicopathologic characteristics associated with overall survival in were analyzed by Cox regression. In addition, we explored the correlation between NLRP3 and immune infiltrates. GSEA and co-expressed gene with NLRP3 were also done in this study. Results: NLRP3 expressed disparately in tumor tissues and normal tissues. Cox regression analysis indicated that up-regulated NLRP3 was an independent prognostic factor for good prognosis in LUAD and SKCM. Logistic regression analysis showed increased NLRP3 expression was significantly correlated with favorable clinicopathologic parameters such as no lymph node invasion and no distant metastasis. Specifically, a positive correlation between increased NLRP3 expression and immune infiltrating level of various immune cells was observed. Conclusion: Together with all these findings, increased NLRP3 expression correlates with favorable prognosis and increased proportion of immune cells in LUAD and SKCM. These conclusions indicate that NLRP3 can serve as a potential biomarker for evaluating prognosis and immune infiltration level.

Download Full-text

Identification and Analysis of Three Hub Prognostic Genes Related to Osteosarcoma Metastasis

Journal of Oncology ◽

10.1155/2021/6646459 ◽

2021 ◽

Vol 2021 ◽

pp. 1-16

Author(s):

Jianye Tan ◽

Haofeng Liang ◽

Bingsheng Yang ◽

Shuang Zhu ◽

Guofeng Wu ◽

...

Keyword(s):

Regression Analysis ◽

Cox Regression ◽

Survival Rates ◽

Prognostic Biomarkers ◽

Messenger Rnas ◽

Hub Genes ◽

Cox Regression Analysis ◽

Expression Levels ◽

Kaplan Meier ◽

Before And After

Osteosarcoma (OS) often occurs in children and often undergoes metastasis, resulting in lower survival rates. Information on the complexity and pathogenic mechanism of OS is limited, and thus, the development of treatments involving alternative molecular and genetic targets is hampered. We categorized transcriptome data into metastasis and nonmetastasis groups, and 400 differential RNAs (230 messenger RNAs (mRNAs) and 170 long noncoding RNAs (lncRNAs)) were obtained by the edgeR package. Prognostic genes were identified by performing univariate Cox regression analysis and the Kaplan–Meier (KM) survival analysis. We then examined the correlation between the expression level of prognostic lncRNAs and mRNAs. Furthermore, microRNAs (miRNAs) corresponding to the coexpression of lncRNA-mRNA was predicted, which was used to construct a competitive endogenous RNA (ceRNA) regulatory network. Finally, multivariate Cox proportional risk regression analysis was used to identify hub prognostic genes. Three hub prognostic genes (ABCG8, LOXL4, and PDE1B) were identified as potential prognostic biomarkers and therapeutic targets for OS. Furthermore, transcriptions factors (TFs) (DBP, ESX1, FOS, FOXI1, MEF2C, NFE2, and OTX2) and lncRNAs (RP11-357H14.16, RP11-284N8.3, and RP11-629G13.1) that were able to affect the expression levels of genes before and after transcription were found to regulate the prognostic hub genes. In addition, we identified drugs related to the prognostic hub genes, which may have potential clinical applications. Immunohistochemistry (IHC) and quantitative real-time polymerase chain reaction (qRT-PCR) confirmed that the expression levels of ABCG8, LOXL4, and PDE1B coincided with the results of bioinformatics analysis. Moreover, the relationship between the hub prognostic gene expression and patient prognosis was also validated. Our study elucidated the roles of three novel prognostic biomarkers in the pathogenesis of OS as well as presenting a potential clinical treatment for OS.

Download Full-text

Predictive Value of Atrial Electromechanical Delay on Long-Term Cardiovascular Outcomes in Hemodialysis Patients

American Journal of Nephrology ◽

10.1159/000441099 ◽

2015 ◽

Vol 42 (3) ◽

pp. 239-249 ◽

Cited By ~ 2

Author(s):

Kultigin Turkmen ◽

Levent Demirtas ◽

Ergun Topal ◽

Abduzhappar Gaipov ◽

Ismail Kocyigit ◽

...

Keyword(s):

Regression Analysis ◽

Total Cholesterol ◽

Cox Regression ◽

Healthy Individuals ◽

Electromechanical Delay ◽

Cox Regression Analysis ◽

Atrial Electromechanical Delay ◽

Kaplan Meier ◽

All Cause Mortality ◽

Spearman Test

Background: Atrial electromechanical delay (AEMD) times were considered independent predictors of cardiovascular morbidity among the general population. We aimed at evaluating AEMD times and other risk factors associated with 2-year combined cardiovascular (CV) events in HD patients. Material and Methods: Sixty hemodialysis (HD) and 44 healthy individuals were enrolled in this prospective study. Echocardiography was performed before the mid-week dialysis session for HD patients. Data were expressed as mean ± SD. Spearman test was used to assess linear associations. Survival was examined with the Kaplan-Meier method. Multivariate Cox regression analysis was used to determine the predictors of combined CV events in this cohort. Results: At the beginning of the study, left intra-atrial-AEMD times were significantly longer in HD patients compared to the left intra-atrial-AEMD times in healthy individuals. After 24 months, 41 patients were still on HD treatment and 19 (31.6%) had died. Serum triglyceride, total cholesterol and albumin were found to be higher and C-reactive protein (CRP) levels, left intra-atrial EMD time (LIAT) and interatrial EMD times were found to be lower in survived HD patients. With the cut-off median values of 3.5 g/dl for albumin, 0.87 mg/dl for CRP, 157 mg/dl for total cholesterol and 151 mg/dl for triglyceride, the Kaplan-Meier curves demonstrated significant differences in terms of all-cause mortality. We also demonstrated the Kaplan-Meier survival curves of HD patients according to tertile values of LIAT. Cox regression analysis revealed that increased CRP and higher LIAT were found to be independent predictors of combined CV events. Conclusions: Increased LIAT and inflammation were found to be closely associated with 2 years combined CV events and all-cause mortality in HD patients.

Download Full-text

Association of masseter area and radiodensity with three-month survival after proximal anterior circulation occlusion

Journal of NeuroInterventional Surgery ◽

10.1136/neurintsurg-2020-015837 ◽

2020 ◽

Vol 13 (1) ◽

pp. 25-29 ◽

Cited By ~ 1

Author(s):

Iisa Lindström ◽

Sara Protto ◽

Niina Khan ◽

Jussi Hernesniemi ◽

Niko Sillanpää ◽

...

Keyword(s):

Regression Analysis ◽

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Cox Regression ◽

Multivariable Logistic Regression Analysis ◽

Anterior Circulation ◽

Term Survival ◽

Cox Regression Analysis ◽

Kaplan Meier

BackgroundMasseter area (MA), a surrogate for sarcopenia, appears to be useful when estimating postoperative survival, but there is lack of consensus regarding the potential predictive value of sarcopenia in acute ischemic stroke (AIS) patients. We hypothesized that MA and density (MD) evaluated from pre-interventional CT angiography scans predict postinterventional survival in patients undergoing mechanical thrombectomy (MT).Materials and methods312 patients treated with MT for acute occlusions of the internal carotid artery (ICA) or the M1 segment of the middle cerebral artery (M1-MCA) between 2013 and 2018. Median follow-up was 27.4 months (range 0–70.4). Binary logistic (alive at 3 months, OR <1) and Cox regression analyses were used to study the effect of MA and MD averages (MAavg and MDavg) on survival.ResultsIn Kaplan–Meier analysis, there was a significant inverse relationship with both MDavg and MAavg and mortality (MDavg P<0.001, MAavg P=0.002). Long-term mortality was 19.6% (n=61) and 3-month mortality 12.2% (n=38). In multivariable logistic regression analysis at 3 months, per 1-SD increase MDavg (OR 0.61, 95% CI 0.41 to 0.92, P=0.018:) and MAavg (OR 0.57, 95% CI 0.35 to 0.91, P=0.019) were the independent predictors associated with lower mortality. In Cox regression analysis, MDavg and MAavg were not associated with long-term survival.ConclusionsIn acute ischemic stroke patients, MDavg and MAavg are independent predictors of 3-month survival after MT of the ICA or M1-MCA. A 1-SD increase in MDavg and MAavg was associated with a 39%–43% decrease in the probability of death during the first 3 months after MT.

Download Full-text

Prognostic value of D-dimer/fibrinogen ratio in the adverse outcomes of patients hospitalized for heart failure

Biomarkers in Medicine ◽

10.2217/bmm-2020-0553 ◽

2020 ◽

Vol 14 (18) ◽

pp. 1733-1745

Author(s):

Tian-Jun Zhao ◽

Qian-Kun Yang ◽

Chun-Yu Tan ◽

Li-Dan Bi ◽

Jie Li ◽

...

Keyword(s):

Heart Failure ◽

Regression Analysis ◽

Cox Regression ◽

Prognostic Indicator ◽

Adverse Outcomes ◽

Rank Test ◽

Clinical Value ◽

Cox Regression Analysis ◽

Kaplan Meier ◽

D Dimer

Aim: To evaluate the clinical value of plasma D-dimer/fibrinogen ratio (DFR) in patients hospitalized for heart failure (HF). Methods: Clinical data of 235 patients were retrospectively analyzed. Kaplan–Meier method and Cox regression analysis were used to identify significant prognosticators. Results: The Kaplan–Meier analysis showed that a higher DFR level was significantly associated with an increase in the end point outcomes, including HF readmission, thrombotic events and death (log-rank test: p < 0.001). The multivariate Cox regression analysis showed that the high tertile of DFR was significantly associated with the study end points (HR: 2.18; 95% CI: 1.31–3.62; p = 0.003), compared with the low tertile. Conclusion: DFR is a reliable prognostic indicator for patients hospitalized for HF.

Download Full-text

Impact of Early C-Reactive Protein/Albumin Ratio on Intra-Hospital Mortality Among Patients with Spontaneous Intracerebral Hemorrhage

Journal of Clinical Medicine ◽

10.3390/jcm9041236 ◽

2020 ◽

Vol 9 (4) ◽

pp. 1236 ◽

Cited By ~ 2

Author(s):

Michael Bender ◽

Kristin Haferkorn ◽

Michaela Friedrich ◽

Eberhard Uhl ◽

Marco Stein

Keyword(s):

Regression Analysis ◽

Intracerebral Hemorrhage ◽

Hospital Mortality ◽

Cox Regression ◽

Spontaneous Intracerebral Hemorrhage ◽

C Reactive Protein ◽

Albumin Ratio ◽

Cox Regression Analysis ◽

Reactive Protein ◽

The Impact

Objective: The impact of increased C-reactive protein (CRP)/albumin ratio on intra-hospital mortality has been investigated among patients admitted to general intensive care units (ICU). However, it was not investigated among patients with spontaneous intracerebral hemorrhage (ICH). This study aimed to investigate the impact of CRP/albumin ratio on intra-hospital mortality in patients with ICH. Patients and Methods: This retrospective study was conducted on 379 ICH patients admitted between 02/2008 and 12/2017. Blood samples were drawn upon admission and the patients’ demographic, medical, and radiological data were collected. The identification of the independent prognostic factors for intra-hospital mortality was calculated using binary logistic regression and COX regression analysis. Results: Multivariate regression analysis shows that higher CRP/albumin ratio (odds ratio (OR) = 1.66, 95% confidence interval (CI) = 1.193–2.317, p = 0.003) upon admission is an independent predictor of intra-hospital mortality. Multivariate Cox regression analysis indicated that an increase of 1 in the CRP/albumin ratio was associated with a 15.3% increase in the risk of intra-hospital mortality (hazard ratio = 1.153, 95% CI = 1.005–1.322, p = 0.42). Furthermore, a CRP/albumin ratio cut-off value greater than 1.22 was associated with increased intra-hospital mortality (Youden’s Index = 0.19, sensitivity = 28.8, specificity = 89.9, p = 0.007). Conclusions: A CRP/albumin ratio greater than 1.22 upon admission was significantly associated with intra-hospital mortality in the ICH patients.

Download Full-text