Hepatic disease control in patients with intrahepatic cholangiocarcinoma correlates with overall survival

Kevin C Soares; Joshua S Jolissaint; Sarah M McIntyre; Kenneth P Seier; Mithat Gönen; Carlie Sigel; Naaz Nasar; Andrea Cercek; James J Harding; Nancy E Kemeny; Louise C Connell; Bas Groot Koerkamp; Vinod P Balachandran; Michael I D'Angelica; Jeffrey A Drebin; T Peter Kingham; Alice C Wei; William R Jarnagin

doi:10.1002/cam4.5925

Hepatic disease control in patients with intrahepatic cholangiocarcinoma correlates with overall survival

Kevin C Soares, Joshua S Jolissaint, Sarah M McIntyre, Kenneth P Seier, Mithat Gönen, Carlie Sigel, Naaz Nasar, Andrea Cercek, James J Harding, Nancy E Kemeny, Louise C Connell, Bas Groot Koerkamp, Vinod P Balachandran, Michael I D'Angelica, Jeffrey A Drebin, T Peter Kingham, Alice C Wei, William R Jarnagin^*

^*Corresponding author for this work

Surgery

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Abstract

Purpose: The role of locoregional therapy compared to systemic chemotherapy (SYS) for unresectable intrahepatic cholangiocarcinoma (IHC) remains controversial. The importance of hepatic disease control, either as initial or salvage therapy, is also unclear. We compared overall survival (OS) in patients treated with resection, hepatic arterial infusion pump (HAIP) chemotherapy, or SYS as it relates to hepatic recurrence or progression. We also evaluated recurrence after resection to determine the efficacy of locoregional salvage therapy. Patients and Methods: In this single-institution retrospective analysis, patients with biopsy-proven IHC treated with either curative-intent resection, HAIP (with or without SYS), or SYS alone were analyzed. Propensity score matching (PSM) was used to compare patients with liver-limited, advanced disease treated with HAIP versus SYS. The impact of locoregional salvage therapies in patients with liver-limited recurrence was analyzed in the resection cohort. Results: From 2000 to 2017, 714 patients with IHC were treated, 219 (30.7%) with resectable disease, 316 (44.3%) with locally advanced disease, and 179 (25.1%) with metastatic disease. Resected patients were less likely to recur or progress in the liver (hazard ratio [HR] 0.41, 95% CI 0.34–0.45) versus those that received HAIP or SYS (HR 0.58, 95% CI 0.50–0.65 vs. HR 0.63, 95% CI 0.57–0.69, respectively). In resected patients, 161 (64.4%) recurred, with 65 liver-only recurrences. Thirty of these patients received subsequent locoregional therapy. On multivariable analysis, locoregional therapy was associated with improved OS after isolated liver recurrence (HR 0.46, 95% CI 0.29–0.75; p = 0.002). In patients with locally advanced unresectable or multifocal liver disease (with or without distant organ metastases), PSM demonstrated improved hepatic progression-free survival in patients treated with HAIP versus SYS (HR 0.65; 95% CI 0.46–0.91; p = 0.01), which correlated with improved OS (HR 0.59, 95% CI 0.43–0.80; p < 0.001). Conclusion: In patients with liver-limited IHC, hepatic disease control is associated with improved OS, emphasizing the potential importance of liver-directed therapy.

Original language	English
Pages (from-to)	12272-12284
Number of pages	13
Journal	Cancer Medicine
Volume	12
Issue number	11
Early online date	16 Apr 2023
DOIs	https://doi.org/10.1002/cam4.5925
Publication status	Published - Jun 2023

Bibliographical note

Funding Information:
We gratefully acknowledge Erin Patterson, PhD (Memorial Sloan Kettering Cancer Center [MSKCC]) and Jessica Massler, LSW (MSKCC) for editorial assistance. The authors would also like to thank the following for fundraising support: Cycle for Survival Teams, Here Comes the Sun, Notorious HPB, Team Dany Testa, and The Jersey Girls.

Funding Information:
This work was supported in part by the Marie‐Josée and Henry R. Kravis Center for Molecular Oncology, the National Cancer Institute (P30‐CA008748; U01CA238444 to W.J.); and the National Center for Advancing Translational Sciences/Weill Cornell Medical College Clinical Translational Science Center (UL1‐TR002318444).

Publisher Copyright:
© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

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Hepatic disease control in patients with intrahepatic cholangiocarcinoma correlates with overall survivalFinal published version, 1.67 MBLicence: CC BY

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Soares, K. C., Jolissaint, J. S., McIntyre, S. M., Seier, K. P., Gönen, M., Sigel, C., Nasar, N., Cercek, A., Harding, J. J., Kemeny, N. E., Connell, L. C., Koerkamp, B. G., Balachandran, V. P., D'Angelica, M. I., Drebin, J. A., Kingham, T. P., Wei, A. C., & Jarnagin, W. R. (2023). Hepatic disease control in patients with intrahepatic cholangiocarcinoma correlates with overall survival. Cancer Medicine, 12(11), 12272-12284. https://doi.org/10.1002/cam4.5925

@article{44f8fe84714c4e709e2d015893fb6fe6,

title = "Hepatic disease control in patients with intrahepatic cholangiocarcinoma correlates with overall survival",

abstract = "Purpose: The role of locoregional therapy compared to systemic chemotherapy (SYS) for unresectable intrahepatic cholangiocarcinoma (IHC) remains controversial. The importance of hepatic disease control, either as initial or salvage therapy, is also unclear. We compared overall survival (OS) in patients treated with resection, hepatic arterial infusion pump (HAIP) chemotherapy, or SYS as it relates to hepatic recurrence or progression. We also evaluated recurrence after resection to determine the efficacy of locoregional salvage therapy. Patients and Methods: In this single-institution retrospective analysis, patients with biopsy-proven IHC treated with either curative-intent resection, HAIP (with or without SYS), or SYS alone were analyzed. Propensity score matching (PSM) was used to compare patients with liver-limited, advanced disease treated with HAIP versus SYS. The impact of locoregional salvage therapies in patients with liver-limited recurrence was analyzed in the resection cohort. Results: From 2000 to 2017, 714 patients with IHC were treated, 219 (30.7%) with resectable disease, 316 (44.3%) with locally advanced disease, and 179 (25.1%) with metastatic disease. Resected patients were less likely to recur or progress in the liver (hazard ratio [HR] 0.41, 95% CI 0.34–0.45) versus those that received HAIP or SYS (HR 0.58, 95% CI 0.50–0.65 vs. HR 0.63, 95% CI 0.57–0.69, respectively). In resected patients, 161 (64.4%) recurred, with 65 liver-only recurrences. Thirty of these patients received subsequent locoregional therapy. On multivariable analysis, locoregional therapy was associated with improved OS after isolated liver recurrence (HR 0.46, 95% CI 0.29–0.75; p = 0.002). In patients with locally advanced unresectable or multifocal liver disease (with or without distant organ metastases), PSM demonstrated improved hepatic progression-free survival in patients treated with HAIP versus SYS (HR 0.65; 95% CI 0.46–0.91; p = 0.01), which correlated with improved OS (HR 0.59, 95% CI 0.43–0.80; p < 0.001). Conclusion: In patients with liver-limited IHC, hepatic disease control is associated with improved OS, emphasizing the potential importance of liver-directed therapy.",

author = "Soares, {Kevin C} and Jolissaint, {Joshua S} and McIntyre, {Sarah M} and Seier, {Kenneth P} and Mithat G{\"o}nen and Carlie Sigel and Naaz Nasar and Andrea Cercek and Harding, {James J} and Kemeny, {Nancy E} and Connell, {Louise C} and Koerkamp, {Bas Groot} and Balachandran, {Vinod P} and D'Angelica, {Michael I} and Drebin, {Jeffrey A} and Kingham, {T Peter} and Wei, {Alice C} and Jarnagin, {William R}",

note = "Funding Information: We gratefully acknowledge Erin Patterson, PhD (Memorial Sloan Kettering Cancer Center [MSKCC]) and Jessica Massler, LSW (MSKCC) for editorial assistance. The authors would also like to thank the following for fundraising support: Cycle for Survival Teams, Here Comes the Sun, Notorious HPB, Team Dany Testa, and The Jersey Girls. Funding Information: This work was supported in part by the Marie‐Jos{\'e}e and Henry R. Kravis Center for Molecular Oncology, the National Cancer Institute (P30‐CA008748; U01CA238444 to W.J.); and the National Center for Advancing Translational Sciences/Weill Cornell Medical College Clinical Translational Science Center (UL1‐TR002318444). Publisher Copyright: {\textcopyright} 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.",

year = "2023",

month = jun,

doi = "10.1002/cam4.5925",

language = "English",

volume = "12",

pages = "12272--12284",

journal = "Cancer Medicine",

issn = "2045-7634",

publisher = "John Wiley & Sons Inc.",

number = "11",

}

Soares, KC, Jolissaint, JS, McIntyre, SM, Seier, KP, Gönen, M, Sigel, C, Nasar, N, Cercek, A, Harding, JJ, Kemeny, NE, Connell, LC, Koerkamp, BG, Balachandran, VP, D'Angelica, MI, Drebin, JA, Kingham, TP, Wei, AC & Jarnagin, WR 2023, 'Hepatic disease control in patients with intrahepatic cholangiocarcinoma correlates with overall survival', Cancer Medicine, vol. 12, no. 11, pp. 12272-12284. https://doi.org/10.1002/cam4.5925

TY - JOUR

T1 - Hepatic disease control in patients with intrahepatic cholangiocarcinoma correlates with overall survival

AU - Soares, Kevin C

AU - Jolissaint, Joshua S

AU - McIntyre, Sarah M

AU - Seier, Kenneth P

AU - Gönen, Mithat

AU - Sigel, Carlie

AU - Nasar, Naaz

AU - Cercek, Andrea

AU - Harding, James J

AU - Kemeny, Nancy E

AU - Connell, Louise C

AU - Koerkamp, Bas Groot

AU - Balachandran, Vinod P

AU - D'Angelica, Michael I

AU - Drebin, Jeffrey A

AU - Kingham, T Peter

AU - Wei, Alice C

AU - Jarnagin, William R

N1 - Funding Information: We gratefully acknowledge Erin Patterson, PhD (Memorial Sloan Kettering Cancer Center [MSKCC]) and Jessica Massler, LSW (MSKCC) for editorial assistance. The authors would also like to thank the following for fundraising support: Cycle for Survival Teams, Here Comes the Sun, Notorious HPB, Team Dany Testa, and The Jersey Girls. Funding Information: This work was supported in part by the Marie‐Josée and Henry R. Kravis Center for Molecular Oncology, the National Cancer Institute (P30‐CA008748; U01CA238444 to W.J.); and the National Center for Advancing Translational Sciences/Weill Cornell Medical College Clinical Translational Science Center (UL1‐TR002318444). Publisher Copyright: © 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

PY - 2023/6

Y1 - 2023/6

N2 - Purpose: The role of locoregional therapy compared to systemic chemotherapy (SYS) for unresectable intrahepatic cholangiocarcinoma (IHC) remains controversial. The importance of hepatic disease control, either as initial or salvage therapy, is also unclear. We compared overall survival (OS) in patients treated with resection, hepatic arterial infusion pump (HAIP) chemotherapy, or SYS as it relates to hepatic recurrence or progression. We also evaluated recurrence after resection to determine the efficacy of locoregional salvage therapy. Patients and Methods: In this single-institution retrospective analysis, patients with biopsy-proven IHC treated with either curative-intent resection, HAIP (with or without SYS), or SYS alone were analyzed. Propensity score matching (PSM) was used to compare patients with liver-limited, advanced disease treated with HAIP versus SYS. The impact of locoregional salvage therapies in patients with liver-limited recurrence was analyzed in the resection cohort. Results: From 2000 to 2017, 714 patients with IHC were treated, 219 (30.7%) with resectable disease, 316 (44.3%) with locally advanced disease, and 179 (25.1%) with metastatic disease. Resected patients were less likely to recur or progress in the liver (hazard ratio [HR] 0.41, 95% CI 0.34–0.45) versus those that received HAIP or SYS (HR 0.58, 95% CI 0.50–0.65 vs. HR 0.63, 95% CI 0.57–0.69, respectively). In resected patients, 161 (64.4%) recurred, with 65 liver-only recurrences. Thirty of these patients received subsequent locoregional therapy. On multivariable analysis, locoregional therapy was associated with improved OS after isolated liver recurrence (HR 0.46, 95% CI 0.29–0.75; p = 0.002). In patients with locally advanced unresectable or multifocal liver disease (with or without distant organ metastases), PSM demonstrated improved hepatic progression-free survival in patients treated with HAIP versus SYS (HR 0.65; 95% CI 0.46–0.91; p = 0.01), which correlated with improved OS (HR 0.59, 95% CI 0.43–0.80; p < 0.001). Conclusion: In patients with liver-limited IHC, hepatic disease control is associated with improved OS, emphasizing the potential importance of liver-directed therapy.

AB - Purpose: The role of locoregional therapy compared to systemic chemotherapy (SYS) for unresectable intrahepatic cholangiocarcinoma (IHC) remains controversial. The importance of hepatic disease control, either as initial or salvage therapy, is also unclear. We compared overall survival (OS) in patients treated with resection, hepatic arterial infusion pump (HAIP) chemotherapy, or SYS as it relates to hepatic recurrence or progression. We also evaluated recurrence after resection to determine the efficacy of locoregional salvage therapy. Patients and Methods: In this single-institution retrospective analysis, patients with biopsy-proven IHC treated with either curative-intent resection, HAIP (with or without SYS), or SYS alone were analyzed. Propensity score matching (PSM) was used to compare patients with liver-limited, advanced disease treated with HAIP versus SYS. The impact of locoregional salvage therapies in patients with liver-limited recurrence was analyzed in the resection cohort. Results: From 2000 to 2017, 714 patients with IHC were treated, 219 (30.7%) with resectable disease, 316 (44.3%) with locally advanced disease, and 179 (25.1%) with metastatic disease. Resected patients were less likely to recur or progress in the liver (hazard ratio [HR] 0.41, 95% CI 0.34–0.45) versus those that received HAIP or SYS (HR 0.58, 95% CI 0.50–0.65 vs. HR 0.63, 95% CI 0.57–0.69, respectively). In resected patients, 161 (64.4%) recurred, with 65 liver-only recurrences. Thirty of these patients received subsequent locoregional therapy. On multivariable analysis, locoregional therapy was associated with improved OS after isolated liver recurrence (HR 0.46, 95% CI 0.29–0.75; p = 0.002). In patients with locally advanced unresectable or multifocal liver disease (with or without distant organ metastases), PSM demonstrated improved hepatic progression-free survival in patients treated with HAIP versus SYS (HR 0.65; 95% CI 0.46–0.91; p = 0.01), which correlated with improved OS (HR 0.59, 95% CI 0.43–0.80; p < 0.001). Conclusion: In patients with liver-limited IHC, hepatic disease control is associated with improved OS, emphasizing the potential importance of liver-directed therapy.

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U2 - 10.1002/cam4.5925

DO - 10.1002/cam4.5925

M3 - Article

C2 - 37062071

SN - 2045-7634

VL - 12

SP - 12272

EP - 12284

JO - Cancer Medicine

JF - Cancer Medicine

IS - 11

ER -

Hepatic disease control in patients with intrahepatic cholangiocarcinoma correlates with overall survival

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