Meredith C Mason1, Nader N Massarweh2,3,4, Ching-Wei D Tzeng1, Yi-Ju Chiang1, Yun Shin Chun1, Thomas A Aloia1, Milind Javle5, Jean-Nicolas Vauthey1, Hop S Tran Cao6. 1. Hepato-Pancreato-Biliary Section, Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. 2. Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey VA Medical Center, Houston, TX, USA. 3. Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX, USA. 4. Section of Health Services Research, Department of Medicine, Baylor College of Medicine, Houston, TX, USA. 5. Department of GI Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. 6. Hepato-Pancreato-Biliary Section, Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. hstran@mdanderson.org.
Abstract
BACKGROUND: While surgery is a mainstay of curative-intent treatment for patients with intrahepatic cholangiocarcinoma (IHC), the role of neoadjuvant therapy (NT) has not been well-established. We sought to describe trends in NT utilization, characterize associated factors, and evaluate association with overall survival (OS). METHODS: Retrospective cohort study of 4456 surgically resected IHC patients within National Cancer Data Base (2006-2016). NT included chemotherapy alone and/or (chemo)radiation. Descriptive statistics used to describe the cohort. Multivariable hierarchical logistic regression models were used to examine factors associated with NT administration. Analyses conducted comparing OS among upfront surgery patients and NT patients using propensity matching using nearest-neighbor methodology and adjustment using inverse probability of treatment weighting (IPTW). Association between NT and risk of death evaluated using multivariable Cox shared frailty modeling. RESULTS: Utilization of NT did not significantly increase over time (11%-2006 to 16%-2016, trend test p = 0.07) but did increase among patients with clinical nodal involvement (cN+, 13% to 36%, p = 0.002). Factors associated with NT use include cN+ disease (odds ratio [OR] 1.68, 95% confidence interval [CI] 1.31-2.15) and advanced clinical T stage: T2 (OR 1.65, 95% CI 1.33-2.06); T3 (OR 1.51, 95% CI 1.13-2.02). After propensity matching, NT associated with a 23% decreased risk of death relative to upfront surgery (hazard ratio [HR] 0.77, 95% CI 0.61-0.97). Findings were similar after IPTW (HR 0.83, 95% CI 0.78-0.88). CONCLUSIONS: NT is increasingly used for the management of IHC patients with characteristics indicating aggressive tumor biology and is associated with decreased risk of death. These data suggest need for prospective studies of NT in management of patients with potentially resectable IHC.
BACKGROUND: While surgery is a mainstay of curative-intent treatment for patients with intrahepatic cholangiocarcinoma (IHC), the role of neoadjuvant therapy (NT) has not been well-established. We sought to describe trends in NT utilization, characterize associated factors, and evaluate association with overall survival (OS). METHODS: Retrospective cohort study of 4456 surgically resected IHC patients within National Cancer Data Base (2006-2016). NT included chemotherapy alone and/or (chemo)radiation. Descriptive statistics used to describe the cohort. Multivariable hierarchical logistic regression models were used to examine factors associated with NT administration. Analyses conducted comparing OS among upfront surgery patients and NT patients using propensity matching using nearest-neighbor methodology and adjustment using inverse probability of treatment weighting (IPTW). Association between NT and risk of death evaluated using multivariable Cox shared frailty modeling. RESULTS: Utilization of NT did not significantly increase over time (11%-2006 to 16%-2016, trend test p = 0.07) but did increase among patients with clinical nodal involvement (cN+, 13% to 36%, p = 0.002). Factors associated with NT use include cN+ disease (odds ratio [OR] 1.68, 95% confidence interval [CI] 1.31-2.15) and advanced clinical T stage: T2 (OR 1.65, 95% CI 1.33-2.06); T3 (OR 1.51, 95% CI 1.13-2.02). After propensity matching, NT associated with a 23% decreased risk of death relative to upfront surgery (hazard ratio [HR] 0.77, 95% CI 0.61-0.97). Findings were similar after IPTW (HR 0.83, 95% CI 0.78-0.88). CONCLUSIONS: NT is increasingly used for the management of IHC patients with characteristics indicating aggressive tumor biology and is associated with decreased risk of death. These data suggest need for prospective studies of NT in management of patients with potentially resectable IHC.