Age and Tumor Stage Interplay in Intrahepatic Cholangiocarcinoma: Prognostic Factors, Mortality Trends, and Therapeutic Implications from a SEER-Based Analysis

Background: Intrahepatic cholangiocarcinoma (ICC), a malignancy originating from the epithelial cells of bile ducts, has shown a notable rise in its incidence over the years. It ranks as the second most frequent primary liver cancer after hepatocellular carcinoma. This study investigates how indepen...

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Main Authors: Ayrton Bangolo, Vignesh K. Nagesh, Hadrian Hoang-Vu Tran, Brooke Sens, Daniel Elias, Behzad Amoozgar, Chase Tomasino, Izage Kianifar Aguilar, Charlene Mansour, Elizabeth Gagen, Lili Zhang, Sarvarinder Gill, Nisrene Jebara, Emma Madigan, Christin Candela, Dohaa Amin, Peter Giunta, Shubhangi Singh, Aman Siddiqui, Auda Auda, Paul Peej, Timophyll Y. H. Fong, Simcha Weissman, Printhia Matshi Lihau, John Bukasa-Kakamba
Format: Article
Language:English
Published: MDPI AG 2025-01-01
Series:Diseases
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Online Access:https://www.mdpi.com/2079-9721/13/2/31
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author Ayrton Bangolo
Vignesh K. Nagesh
Hadrian Hoang-Vu Tran
Brooke Sens
Daniel Elias
Behzad Amoozgar
Chase Tomasino
Izage Kianifar Aguilar
Charlene Mansour
Elizabeth Gagen
Lili Zhang
Sarvarinder Gill
Nisrene Jebara
Emma Madigan
Christin Candela
Dohaa Amin
Peter Giunta
Shubhangi Singh
Aman Siddiqui
Auda Auda
Paul Peej
Timophyll Y. H. Fong
Simcha Weissman
Printhia Matshi Lihau
John Bukasa-Kakamba
author_facet Ayrton Bangolo
Vignesh K. Nagesh
Hadrian Hoang-Vu Tran
Brooke Sens
Daniel Elias
Behzad Amoozgar
Chase Tomasino
Izage Kianifar Aguilar
Charlene Mansour
Elizabeth Gagen
Lili Zhang
Sarvarinder Gill
Nisrene Jebara
Emma Madigan
Christin Candela
Dohaa Amin
Peter Giunta
Shubhangi Singh
Aman Siddiqui
Auda Auda
Paul Peej
Timophyll Y. H. Fong
Simcha Weissman
Printhia Matshi Lihau
John Bukasa-Kakamba
author_sort Ayrton Bangolo
collection DOAJ
description Background: Intrahepatic cholangiocarcinoma (ICC), a malignancy originating from the epithelial cells of bile ducts, has shown a notable rise in its incidence over the years. It ranks as the second most frequent primary liver cancer after hepatocellular carcinoma. This study investigates how independent prognostic factors, specifically, age and tumor stage, interact to impact mortality in ICC patients. Furthermore, it examines the clinical features, survival rates, and prognostic indicators of ICC cases diagnosed between 2010 and 2017. Methods: Using data from 5083 patients obtained from the Surveillance, Epidemiology, and End Results (SEER) database, this study evaluated demographic and clinical factors alongside overall mortality (OM) and cancer-specific mortality (CSM). Variables achieving a <i>p</i>-value below 0.1 in univariate Cox regression analysis were incorporated into multivariate Cox regression models to identify independent prognostic factors. Hazard ratios (HRs) exceeding 1 were interpreted as markers of poor prognosis. Additionally, this study explored the interaction between age and tumor stage in shaping survival outcomes. Results: The multivariate Cox proportional hazards analysis indicated higher OM in males (HR = 1.19, 95% CI: 1.12–1.26, <i>p</i> < 0.01) and residents of metropolitan counties with populations exceeding 250,000 (HR = 1.15, 95% CI: 1.01–1.31, <i>p</i> < 0.05). Conversely, lower OM was observed in individuals aged 40–59 years (HR = 0.58, 95% CI: 0.38–0.89, <i>p</i> < 0.05), those aged 60–79 years (HR = 0.65, 95% CI: 0.43–0.98, <i>p</i> < 0.05), and patients who received radiation therapy (HR = 0.78, 95% CI: 0.72–0.85, <i>p</i> < 0.01), chemotherapy (HR = 0.54, 95% CI: 0.51–0.58, <i>p</i> < 0.01), or surgery (HR = 0.29, 95% CI: 0.26–0.31, <i>p</i> < 0.01). For CSM, males exhibited higher risks (HR = 1.17, 95% CI: 1.10–1.25, <i>p</i> < 0.01), as did individuals in metropolitan counties with populations over 250,000 (HR = 1.18, 95% CI: 1.03–1.35, <i>p</i> < 0.05). Reduced CSM was observed in patients aged 40–59 years (HR = 0.52, 95% CI: 0.34–0.79, <i>p</i> < 0.01), those aged 60–79 years (HR = 0.57, 95% CI: 0.38–0.86, <i>p</i> < 0.01), and those undergoing radiation therapy (HR = 0.76, 95% CI: 0.70–0.83, <i>p</i> < 0.01), chemotherapy (HR = 0.55, 95% CI: 0.51–0.59, <i>p</i> < 0.01), or surgery (HR = 0.27, 95% CI: 0.25–0.30, <i>p</i> < 0.01). When examining the interaction between age and tumor stage, higher OM was observed in patients aged 40–59 with tumors involving lymph nodes (HR = 1.26, 95% CI: 1.14–2.67, <i>p</i> < 0.05). Similarly, CSM was elevated in patients aged 40–59 with lymph node involvement alone (HR = 2.60, 95% CI: 1.26–5.36, <i>p</i> < 0.05) or with direct spread (HR = 2.81, 95% CI: 1.04–7.61, <i>p</i> < 0.05). Among those aged 60–79, higher CSM was noted in cases with lymph node involvement only (HR = 2.24, 95% CI: 1.11–4.50, <i>p</i> < 0.05) or lymph node involvement accompanied by direct extension (HR = 2.93, 95% CI: 1.10–7.82, <i>p</i> < 0.05). Conclusions: This retrospective analysis, utilizing data from the SEER database, provides new insights into mortality patterns in intrahepatic cholangiocarcinoma (ICC). This study identifies a significant interplay between two key prognostic factors, emphasizing their collective role in influencing mortality outcomes. Despite the predominance of advanced-stage diagnoses, our analysis underscores the substantial survival benefits associated with treatment interventions, with surgical procedures demonstrating the most pronounced impact. These findings highlight the importance of recognizing patients who may benefit from timely and intensive therapeutic strategies. Furthermore, the results underscore the need for future prospective randomized studies to deepen our understanding of these interactions in ICC, particularly as advancements in precision oncology continue to refine patient care.
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spelling doaj-art-cdf045d399af411b8066cf812643d67c2025-08-20T03:12:11ZengMDPI AGDiseases2079-97212025-01-011323110.3390/diseases13020031Age and Tumor Stage Interplay in Intrahepatic Cholangiocarcinoma: Prognostic Factors, Mortality Trends, and Therapeutic Implications from a SEER-Based AnalysisAyrton Bangolo0Vignesh K. Nagesh1Hadrian Hoang-Vu Tran2Brooke Sens3Daniel Elias4Behzad Amoozgar5Chase Tomasino6Izage Kianifar Aguilar7Charlene Mansour8Elizabeth Gagen9Lili Zhang10Sarvarinder Gill11Nisrene Jebara12Emma Madigan13Christin Candela14Dohaa Amin15Peter Giunta16Shubhangi Singh17Aman Siddiqui18Auda Auda19Paul Peej20Timophyll Y. H. Fong21Simcha Weissman22Printhia Matshi Lihau23John Bukasa-Kakamba24Department of Hematology and Oncology, John Theurer Cancer Center, Hackensack University Medical Center, Hackensack, NJ 07601, USADepartment of Internal Medicine, Hackensack Palisades Medical Center, North Bergen, NJ 07047, USADepartment of Internal Medicine, Hackensack Palisades Medical Center, North Bergen, NJ 07047, USADepartment of Internal Medicine, Hackensack Palisades Medical Center, North Bergen, NJ 07047, USARutgers New Jersey Medical School, Newark, NJ 07103, USADepartment of Hematology and Oncology, John Theurer Cancer Center, Hackensack University Medical Center, Hackensack, NJ 07601, USADepartment of Hematology and Oncology, John Theurer Cancer Center, Hackensack University Medical Center, Hackensack, NJ 07601, USADepartment of Internal Medicine, Hackensack Palisades Medical Center, North Bergen, NJ 07047, USARutgers New Jersey Medical School, Newark, NJ 07103, USADepartment of Internal Medicine, Hackensack Palisades Medical Center, North Bergen, NJ 07047, USADepartment of Hematology and Oncology, John Theurer Cancer Center, Hackensack University Medical Center, Hackensack, NJ 07601, USADepartment of Hematology and Oncology, John Theurer Cancer Center, Hackensack University Medical Center, Hackensack, NJ 07601, USAColumbia University School of Nursing, New York, NY 10032, USADepartment of Internal Medicine, Hackensack Palisades Medical Center, North Bergen, NJ 07047, USADepartment of Internal Medicine, Hackensack Palisades Medical Center, North Bergen, NJ 07047, USADepartment of Internal Medicine, Hackensack Palisades Medical Center, North Bergen, NJ 07047, USADepartment of Internal Medicine, Hackensack Palisades Medical Center, North Bergen, NJ 07047, USADepartment of Internal Medicine, Hackensack Palisades Medical Center, North Bergen, NJ 07047, USADepartment of Family Medicine, Hackensack Palisades Medical Center, North Bergen, NJ 07047, USADepartment of Family Medicine, Hackensack Palisades Medical Center, North Bergen, NJ 07047, USADepartment of Internal Medicine, Hackensack Palisades Medical Center, North Bergen, NJ 07047, USADepartment of Internal Medicine, Hackensack Palisades Medical Center, North Bergen, NJ 07047, USADepartment of Internal Medicine, Hackensack Palisades Medical Center, North Bergen, NJ 07047, USADepartment of Research and Innovation, Congolese National Cancer Control Center, Kinshasa, Democratic Republic of the CongoDepartment of Endocrinology and Nuclear Medicine, Kinshasa University Clinics, Kinshasa, Democratic Republic of the CongoBackground: Intrahepatic cholangiocarcinoma (ICC), a malignancy originating from the epithelial cells of bile ducts, has shown a notable rise in its incidence over the years. It ranks as the second most frequent primary liver cancer after hepatocellular carcinoma. This study investigates how independent prognostic factors, specifically, age and tumor stage, interact to impact mortality in ICC patients. Furthermore, it examines the clinical features, survival rates, and prognostic indicators of ICC cases diagnosed between 2010 and 2017. Methods: Using data from 5083 patients obtained from the Surveillance, Epidemiology, and End Results (SEER) database, this study evaluated demographic and clinical factors alongside overall mortality (OM) and cancer-specific mortality (CSM). Variables achieving a <i>p</i>-value below 0.1 in univariate Cox regression analysis were incorporated into multivariate Cox regression models to identify independent prognostic factors. Hazard ratios (HRs) exceeding 1 were interpreted as markers of poor prognosis. Additionally, this study explored the interaction between age and tumor stage in shaping survival outcomes. Results: The multivariate Cox proportional hazards analysis indicated higher OM in males (HR = 1.19, 95% CI: 1.12–1.26, <i>p</i> < 0.01) and residents of metropolitan counties with populations exceeding 250,000 (HR = 1.15, 95% CI: 1.01–1.31, <i>p</i> < 0.05). Conversely, lower OM was observed in individuals aged 40–59 years (HR = 0.58, 95% CI: 0.38–0.89, <i>p</i> < 0.05), those aged 60–79 years (HR = 0.65, 95% CI: 0.43–0.98, <i>p</i> < 0.05), and patients who received radiation therapy (HR = 0.78, 95% CI: 0.72–0.85, <i>p</i> < 0.01), chemotherapy (HR = 0.54, 95% CI: 0.51–0.58, <i>p</i> < 0.01), or surgery (HR = 0.29, 95% CI: 0.26–0.31, <i>p</i> < 0.01). For CSM, males exhibited higher risks (HR = 1.17, 95% CI: 1.10–1.25, <i>p</i> < 0.01), as did individuals in metropolitan counties with populations over 250,000 (HR = 1.18, 95% CI: 1.03–1.35, <i>p</i> < 0.05). Reduced CSM was observed in patients aged 40–59 years (HR = 0.52, 95% CI: 0.34–0.79, <i>p</i> < 0.01), those aged 60–79 years (HR = 0.57, 95% CI: 0.38–0.86, <i>p</i> < 0.01), and those undergoing radiation therapy (HR = 0.76, 95% CI: 0.70–0.83, <i>p</i> < 0.01), chemotherapy (HR = 0.55, 95% CI: 0.51–0.59, <i>p</i> < 0.01), or surgery (HR = 0.27, 95% CI: 0.25–0.30, <i>p</i> < 0.01). When examining the interaction between age and tumor stage, higher OM was observed in patients aged 40–59 with tumors involving lymph nodes (HR = 1.26, 95% CI: 1.14–2.67, <i>p</i> < 0.05). Similarly, CSM was elevated in patients aged 40–59 with lymph node involvement alone (HR = 2.60, 95% CI: 1.26–5.36, <i>p</i> < 0.05) or with direct spread (HR = 2.81, 95% CI: 1.04–7.61, <i>p</i> < 0.05). Among those aged 60–79, higher CSM was noted in cases with lymph node involvement only (HR = 2.24, 95% CI: 1.11–4.50, <i>p</i> < 0.05) or lymph node involvement accompanied by direct extension (HR = 2.93, 95% CI: 1.10–7.82, <i>p</i> < 0.05). Conclusions: This retrospective analysis, utilizing data from the SEER database, provides new insights into mortality patterns in intrahepatic cholangiocarcinoma (ICC). This study identifies a significant interplay between two key prognostic factors, emphasizing their collective role in influencing mortality outcomes. Despite the predominance of advanced-stage diagnoses, our analysis underscores the substantial survival benefits associated with treatment interventions, with surgical procedures demonstrating the most pronounced impact. These findings highlight the importance of recognizing patients who may benefit from timely and intensive therapeutic strategies. Furthermore, the results underscore the need for future prospective randomized studies to deepen our understanding of these interactions in ICC, particularly as advancements in precision oncology continue to refine patient care.https://www.mdpi.com/2079-9721/13/2/31age-related prognosistumor stageintrahepatic cholangiocarcinomaSEER databasesurvival outcomestherapeutic interventions
spellingShingle Ayrton Bangolo
Vignesh K. Nagesh
Hadrian Hoang-Vu Tran
Brooke Sens
Daniel Elias
Behzad Amoozgar
Chase Tomasino
Izage Kianifar Aguilar
Charlene Mansour
Elizabeth Gagen
Lili Zhang
Sarvarinder Gill
Nisrene Jebara
Emma Madigan
Christin Candela
Dohaa Amin
Peter Giunta
Shubhangi Singh
Aman Siddiqui
Auda Auda
Paul Peej
Timophyll Y. H. Fong
Simcha Weissman
Printhia Matshi Lihau
John Bukasa-Kakamba
Age and Tumor Stage Interplay in Intrahepatic Cholangiocarcinoma: Prognostic Factors, Mortality Trends, and Therapeutic Implications from a SEER-Based Analysis
Diseases
age-related prognosis
tumor stage
intrahepatic cholangiocarcinoma
SEER database
survival outcomes
therapeutic interventions
title Age and Tumor Stage Interplay in Intrahepatic Cholangiocarcinoma: Prognostic Factors, Mortality Trends, and Therapeutic Implications from a SEER-Based Analysis
title_full Age and Tumor Stage Interplay in Intrahepatic Cholangiocarcinoma: Prognostic Factors, Mortality Trends, and Therapeutic Implications from a SEER-Based Analysis
title_fullStr Age and Tumor Stage Interplay in Intrahepatic Cholangiocarcinoma: Prognostic Factors, Mortality Trends, and Therapeutic Implications from a SEER-Based Analysis
title_full_unstemmed Age and Tumor Stage Interplay in Intrahepatic Cholangiocarcinoma: Prognostic Factors, Mortality Trends, and Therapeutic Implications from a SEER-Based Analysis
title_short Age and Tumor Stage Interplay in Intrahepatic Cholangiocarcinoma: Prognostic Factors, Mortality Trends, and Therapeutic Implications from a SEER-Based Analysis
title_sort age and tumor stage interplay in intrahepatic cholangiocarcinoma prognostic factors mortality trends and therapeutic implications from a seer based analysis
topic age-related prognosis
tumor stage
intrahepatic cholangiocarcinoma
SEER database
survival outcomes
therapeutic interventions
url https://www.mdpi.com/2079-9721/13/2/31
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