Chemotherapy predictors and a time-dependent chemotherapy effect in metastatic esophageal cancer

BACKGROUND Chemotherapy has long been shown to confer a survival benefit in patients with metastatic esophageal cancer.However,not all patients with metastatic disease receive chemotherapy.AIM To evaluate a large cancer database of metastatic esophageal cancer cases to identify predictors of receipt to chemotherapy and survival.METHODS We interrogated the National Cancer Database(NCDB)between 2004-2015 and included patients with M1 disease who had received or did not receive chemotherapy.A logistic regression model was used to examine the associations between chemotherapy and potential confounders and a Cox proportional hazards model was employed to examine the effect of chemotherapy on overall survival(OS).Propensity score analyses were further performed to balance measurable confounders between patients treated with and without chemotherapy.RESULTS A total of 29182 patients met criteria for inclusion in this analysis,with 21911(75%)receiving chemotherapy and 7271(25%)not receiving chemotherapy.The median follow-up was 69.45 mo.The median OS for patients receiving chemotherapy was 9.53 mo(9.33-9.72)vs 2.43 mo(2.27-2.60)with no chemotherapy.Year of diagnosis 2010-2014[odds ratio(OR):1.29,95%confidence interval(CI):1.17-1.43,P value<0.001],median income>$46000(OR:1.49,95%CI:1.27-1.75,P value<0.001),and node-positivity(OR:1.35,95%CI:1.20-1.52,P<0.001)were independent predictors of receiving chemotherapy,while female gender(OR:0.86,95%CI:0.76-0.98,P=0.019),black race(OR:0.76,95%CI:0.67-0.93,P=0.005),uninsured status(OR:0.41,95%CI:0.33-0.52,P<0.001),and high Charlson Comorbidity Index(CCI)(OR for CCI≥2:0.61,95%CI:0.50-0.74,P<0.001)predicted for lower odds of receiving chemotherapy.Modeling the effect of chemotherapy on OS using a time-dependent coefficient showed that chemotherapy was associated with improved OS up to 10 mo,after which there is no significant effect on OS.Moreover,uninsured status[hazard ratio(HR):1.20,95%CI:1.09-1.31,P<0.001],being from the geographic Midwest(HR:1.07,95%CI:1.01-1.14,P=0.032),high CCI(HR for CCI≥2:1.16,95%CI:1.07-1.26,P<0.001),and higher tumor grade(HR for grade 3 vs grade 1:1.28,95%CI:1.14-1.44,P<0.001)and higher T stage(HR for T1 vs T4:0.89,95%CI:0.84-0.95,P<0.001)were independent predictors of worse OS on multivariable analyses.CONCLUSION In this large,retrospective NCDB analysis,we identified several socioeconomic and clinicopathologic predictors for receiving chemotherapy and OS in patients with metastatic esophageal cancer.The benefit of chemotherapy on OS is timedependent and favors early initiation.Focused outreach in lower income and underinsured patients is critical as receipt of chemotherapy is associated with improved OS.

Impact of palliative therapies in metastatic esophageal cancer patients not receiving chemotherapy

BACKGROUND Palliative therapy has been associated with improved overall survival(OS)in several tumor types.Not all patients with metastatic esophageal cancer receive palliative chemotherapy,and the roles of other palliative therapies in these patients are limited.AIM To investigate the impact of other palliative therapies in patients with metastatic esophageal cancer not receiving chemotherapy.METHODS The National Cancer Database was used to identify patients between 2004-2015.Patients with M1 disease who declined chemotherapy and had known palliative therapy status[palliative therapies were defined as surgery,radiotherapy(RT),pain management,or any combination thereof]were included.Cases with unknown chemotherapy,RT,or nonprimary surgery status were excluded.Kaplan-Meier estimates of OS were calculated.Cox proportional hazards regression models were employed to examine factors influencing survival.RESULTS Among 140234 esophageal cancer cases,we identified 1493 patients who did not receive chemotherapy and had complete data.Median age was 70 years,most(66.3%)had a Charlson Comorbidity Index(CCI)of 0,and 37.1%were treated at an academic center.The majority(72.7%)did not receive other palliative therapies.On both univariate and multivariable analyses,there was no difference in OS between those receiving other palliative therapy(median 2.83 mo,95%CI:2.53-3.12)vs no palliative therapy(2.37 no,95%CI:2.2-2.56;multivariable P=0.290).On univariate,but not multivariable analysis,treatment at an academic center was predictive of improved OS[Hazard ratio(HR)0.90,95%CI:0.80-1.00;P=0.047].On multivariable analysis,female sex(HR 0.81,95%CI:0.71-0.92)and non-black,other race compared to white race(HR 0.72,95%CI:0.56-0.93)were associated with reduced mortality,while South geographic region relative to West region(HR 1.23,95%CI:1.04-1.46)and CCI of 1 relative to CCI of 0(HR 1.17,95%CI:1.03-1.32)were associated with increased mortality.Higher histologic grade and T-stage were also associated with worse OS(P<0.05).CONCLUSION Palliative therapies other than chemotherapy conferred a numerically higher,but not statistically significant difference in OS among patients with metastatic esophageal cancer not receiving chemotherapy.Quality of life metrics,inpatient status,and subgroup analyses are important for examining the role of palliative therapies other than chemotherapy in metastatic esophageal cancer and future studies are warranted.