Midthun Lauren, Kim Sungjin, Hendifar Andrew, Osipov Arsen, Klempner Samuel J, Chao Joseph, Cho May, Guan Michelle, Placencio-Hickok Veronica R, Gangi Alexandra, Burch Miguel, Lin De-Chen, Waters Kevin, Atkins Katelyn, Kamrava Mitchell, Gong Jun
Department of Medicine, Division of Hematology and Oncology, Cedars-Sinai Medical Center, Los Angeles, CA 90048, United States.
Biostatistics and Bioinformatics Research Center, Cedars Sinai Medical Center, Los Angeles, CA 90048, United States.
World J Gastrointest Oncol. 2022 Feb 15;14(2):511-524. doi: 10.4251/wjgo.v14.i2.511.
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) 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, value < 0.001], median income > $46000 (OR: 1.49, 95%CI: 1.27-1.75, value < 0.001), and node-positivity (OR: 1.35, 95%CI: 1.20-1.52, < 0.001) were independent predictors of receiving chemotherapy, while female gender (OR: 0.86, 95%CI: 0.76-0.98, = 0.019), black race (OR: 0.76, 95%CI: 0.67-0.93, = 0.005), uninsured status (OR: 0.41, 95%CI: 0.33-0.52, < 0.001), and high Charlson Comorbidity Index (CCI) (OR for CCI ≥ 2: 0.61, 95%CI: 0.50-0.74, < 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, < 0.001], being from the geographic Midwest (HR: 1.07, 95%CI: 1.01-1.14, = 0.032), high CCI (HR for CCI ≥ 2: 1.16, 95%CI: 1.07-1.26, < 0.001), and higher tumor grade (HR for grade 3 grade 1: 1.28, 95%CI: 1.14-1.44, < 0.001) and higher T stage (HR for T1 T4: 0.89, 95%CI: 0.84-0.95, < 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 time-dependent and favors early initiation. Focused outreach in lower income and underinsured patients is critical as receipt of chemotherapy is associated with improved OS.
背景:长期以来,化疗已被证明能使转移性食管癌患者的生存期获益。然而,并非所有转移性疾病患者都接受化疗。 目的:评估一个大型转移性食管癌病例癌症数据库,以确定接受化疗及生存的预测因素。 方法:我们查询了2004年至2015年的国家癌症数据库(NCDB),纳入了患有M1期疾病且接受或未接受化疗的患者。使用逻辑回归模型来检验化疗与潜在混杂因素之间的关联,并采用Cox比例风险模型来检验化疗对总生存期(OS)的影响。进一步进行倾向评分分析以平衡接受化疗和未接受化疗患者之间的可测量混杂因素。 结果:共有29182例患者符合纳入本分析的标准,其中21911例(75%)接受化疗,7271例(25%)未接受化疗。中位随访时间为69.45个月。接受化疗患者的中位OS为9.53个月(9.33 - 9.72),未接受化疗患者的中位OS为2.43个月(2.27 - 2.60)。2010 - 2014年诊断(比值比[OR]:1.29,95%置信区间[CI]:1.17 - 1.43,P值<0.001)、中位收入>46000美元(OR:1.49,95%CI:1.27 - 1.75,P值<0.001)以及淋巴结阳性(OR:1.35,95%CI:1.20 - 1.52,P<0.001)是接受化疗的独立预测因素,而女性(OR:0.86,95%CI:0.76 - 0.98,P = 0.019)、黑人种族(OR:0.76,95%CI:0.67 - 0.93,P = 0.005)、未参保状态(OR:0.41,95%CI:0.33 - 0.52,P<0.001)以及高Charlson合并症指数(CCI)(CCI≥2时的OR:0.61,95%CI:0.50 - 0.74,P<0.001)预测接受化疗的几率较低。使用时间依赖系数对化疗对OS的影响进行建模显示,化疗与长达10个月的OS改善相关,之后对OS无显著影响。此外,在多变量分析中,未参保状态[风险比(HR):1.20,95%CI:1.09 - 1.31,P<0.001]、来自中西部地区(HR:1.07,95%CI:1.01 - 1.14,P = 0.032)、高CCI(CCI≥2时的HR:1.16,95%CI:1.07 - 1.26,P<0.001)以及更高的肿瘤分级(3级相对于1级的HR:1.28,95%CI:1.14 - 1.44,P<0.001)和更高的T分期(T1相对于T4的HR:0.89,95%CI:0.84 - 0.95,P<0.001)是OS较差的独立预测因素。 结论:在这项大型回顾性NCDB分析中,我们确定了转移性食管癌患者接受化疗及OS的若干社会经济和临床病理预测因素。化疗对OS的益处是时间依赖性的,且有利于早期开始。对低收入和未充分参保患者进行有针对性的宣传至关重要,因为接受化疗与OS改善相关。
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