Retrospective Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Feb 15, 2022; 14(2): 511-524
Published online Feb 15, 2022. doi: 10.4251/wjgo.v14.i2.511
Chemotherapy predictors and a time-dependent chemotherapy effect in metastatic esophageal cancer
Lauren Midthun, Sungjin Kim, Andrew Hendifar, Arsen Osipov, Samuel J Klempner, Joseph Chao, May Cho, Michelle Guan, Veronica R Placencio-Hickok, Alexandra Gangi, Miguel Burch, De-Chen Lin, Kevin Waters, Katelyn Atkins, Mitchell Kamrava, Jun Gong
Lauren Midthun, Arsen Osipov, Michelle Guan, De-Chen Lin, Jun Gong, Department of Medicine, Division of Hematology and Oncology, Cedars-Sinai Medical Center, Los Angeles, CA 90048, United States
Sungjin Kim, Biostatistics and Bioinformatics Research Center, Cedars Sinai Medical Center, Los Angeles, CA 90048, United States
Andrew Hendifar, Samuel Oschin Cancer Center, Cedars-Sinai Medical Center, Los Angeles, CA 90048, United States
Samuel J Klempner, Department of Medicine, Beth Israel Deaconess Medical Center/Harvard Medical School, Brigham and Women's Hospital/Harvard Medical School, Boston, MA 02114, United States
Joseph Chao, Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, CA 91010, United States
May Cho, Division of Hematology and Oncology, Department of Medicine, University of California, Irvine, CA 92697, United States
Veronica R Placencio-Hickok, Department of Medicine, Cedars Sinai Medical Center, Los Angeles, CA 90048, United States
Alexandra Gangi, Miguel Burch, Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA 90048, United States
Kevin Waters, Department of Pathology and Laboratory Medicine, Cedars Sinai Medical Center, Los Angeles, CA 90048, United States
Katelyn Atkins, Department of Radiation Oncology, Cedars Sinai Medical Center, Los Angeles, CA 90048, United States
Mitchell Kamrava, Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, CA 90048, United States
Author contributions: Kim S and Gong J designed the research; Kim S, Guan M, Placencio-Hickok VR and Gong J collected and analyzed the data; Midthun L, Kim S and Gong J wrote the paper; all authors edited and approved the final paper.
Institutional review board statement: The data used in the study are derived from a de-identified National Cancer Database file. As all patient identification variables have been removed, no institutional review board review was needed.
Informed consent statement: The data used in the study are derived from a de-identified National Cancer Database file. As all subject identification variables have been removed, no informed consent was needed.
Conflict-of-interest statement: No conflict of interest.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Jun Gong, MD, Assistant Professor, Department of Medicine, Division of Hematology and Oncology, Cedars-Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, CA 90048, United States. jun.gong@cshs.org
Received: March 16, 2021
Peer-review started: March 16, 2021
First decision: May 7, 2021
Revised: July 1, 2021
Accepted: December 25, 2022
Article in press: December 25, 2021
Published online: February 15, 2022
Processing time: 331 Days and 13.1 Hours
Abstract
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 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.

Keywords: Esophageal cancer; Metastatic; Chemotherapy; Predictors; Survival

Core Tip: We evaluated a large cancer database of metastatic esophageal cancer cases to identify predictors of receipt to chemotherapy and survival. We confirmed that although palliative, receipt of chemotherapy in metastatic esophageal cancer conferred an overall survival (OS) benefit over no chemotherapy. However, the benefit of this OS benefit with chemotherapy is time-dependent and favors early initiation. Furthermore, several socioeconomic and clinicopathologic factors were predictive for receipt of chemotherapy and OS in this cohort.