Prognostic Factors Change Over Time After Hepatectomy for Colorectal Liver Metastases: A Multi-institutional, International Analysis of 1099 Patients

Georgios Antonios Margonis, Stefan Buettner, Nikolaos Andreatos, Doris Wagner, Kazunari Sasaki, Carlotta Barbon, Andrea Beer, Carsten Kamphues, Inger Marie Løes, Jin He, Timothy M. Pawlik, Klaus Kaczirek, George Poultsides, Per Eystein Lønning, John L Cameron, Hans Joerg Mischinger, Federico N. Aucejo, Martin E. Kreis, Christopher Wolfgang, Matthew J Weiss

Research output: Contribution to journalArticle

Abstract

OBJECTIVE: To evaluate the changing impact of genetic and clinicopathologic factors on conditional overall survival (CS) over time in patients with resectable colorectal liver metastasis. BACKGROUND: CS estimates account for the changing likelihood of survival over time and may reveal the changing impact of prognostic factors as time accrues from the date of surgery. METHODS: CS analysis was performed in 1099 patients of an international, multi-institutional cohort. Three-year CS (CS3) estimates at the "xth" year after surgery were calculated as follows: CS3 = CS (x + 3)/CS (x). The standardized difference (d) between CS3 rates was used to estimate the changing prognostic power of selected variables over time. A d < 0.1 indicated very small differences between groups, 0.1 ≤ d < 0.3 indicated small differences, 0.3 ≤ d < 0.5 indicated moderate differences, and d ≥ 0.5 indicated strong differences. RESULTS: According to OS estimates calculated at the time of surgery, the presence of BRAF and KRAS mutations, R1 margin status, resected extrahepatic disease, patient age, primary tumor lymph node metastasis, tumor number, and carcinoembryonic antigen levels independently predicted worse survival. However, when temporal changes in the prognostic impact of these variables were considered using CS3 estimates, BRAF mutation dominated prognosis during the first year (d = 0.48), whereas surgeon-related variables (ie, surgical margin and resected extrahepatic disease) determined prognosis thereafter (d ≥ 0.5). Traditional clinicopathologic factors affected survival constantly, but only to a moderate degree (0.3 ≤ d < 0.5). CONCLUSIONS: The impact of genetic, surgery-related, and clinicopathologic factors on OS and CS3 changed dramatically over time. Specifically, BRAF mutation status dominated prognosis in the first year, whereas positive surgical margins and resected extrahepatic disease determined prognosis thereafter.

Original languageEnglish (US)
Pages (from-to)1129-1137
Number of pages9
JournalAnnals of surgery
Volume269
Issue number6
DOIs
StatePublished - Jun 1 2019

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Hepatectomy
Neoplasm Metastasis
Survival
Liver
Mutation
Carcinoembryonic Antigen
Neoplasm Antigens
Survival Analysis
Lymph Nodes

ASJC Scopus subject areas

  • Surgery

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Prognostic Factors Change Over Time After Hepatectomy for Colorectal Liver Metastases : A Multi-institutional, International Analysis of 1099 Patients. / Margonis, Georgios Antonios; Buettner, Stefan; Andreatos, Nikolaos; Wagner, Doris; Sasaki, Kazunari; Barbon, Carlotta; Beer, Andrea; Kamphues, Carsten; Løes, Inger Marie; He, Jin; Pawlik, Timothy M.; Kaczirek, Klaus; Poultsides, George; Lønning, Per Eystein; Cameron, John L; Mischinger, Hans Joerg; Aucejo, Federico N.; Kreis, Martin E.; Wolfgang, Christopher; Weiss, Matthew J.

In: Annals of surgery, Vol. 269, No. 6, 01.06.2019, p. 1129-1137.

Research output: Contribution to journalArticle

Margonis, GA, Buettner, S, Andreatos, N, Wagner, D, Sasaki, K, Barbon, C, Beer, A, Kamphues, C, Løes, IM, He, J, Pawlik, TM, Kaczirek, K, Poultsides, G, Lønning, PE, Cameron, JL, Mischinger, HJ, Aucejo, FN, Kreis, ME, Wolfgang, C & Weiss, MJ 2019, 'Prognostic Factors Change Over Time After Hepatectomy for Colorectal Liver Metastases: A Multi-institutional, International Analysis of 1099 Patients', Annals of surgery, vol. 269, no. 6, pp. 1129-1137. https://doi.org/10.1097/SLA.0000000000002664
Margonis, Georgios Antonios ; Buettner, Stefan ; Andreatos, Nikolaos ; Wagner, Doris ; Sasaki, Kazunari ; Barbon, Carlotta ; Beer, Andrea ; Kamphues, Carsten ; Løes, Inger Marie ; He, Jin ; Pawlik, Timothy M. ; Kaczirek, Klaus ; Poultsides, George ; Lønning, Per Eystein ; Cameron, John L ; Mischinger, Hans Joerg ; Aucejo, Federico N. ; Kreis, Martin E. ; Wolfgang, Christopher ; Weiss, Matthew J. / Prognostic Factors Change Over Time After Hepatectomy for Colorectal Liver Metastases : A Multi-institutional, International Analysis of 1099 Patients. In: Annals of surgery. 2019 ; Vol. 269, No. 6. pp. 1129-1137.
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TY - JOUR

T1 - Prognostic Factors Change Over Time After Hepatectomy for Colorectal Liver Metastases

T2 - A Multi-institutional, International Analysis of 1099 Patients

AU - Margonis, Georgios Antonios

AU - Buettner, Stefan

AU - Andreatos, Nikolaos

AU - Wagner, Doris

AU - Sasaki, Kazunari

AU - Barbon, Carlotta

AU - Beer, Andrea

AU - Kamphues, Carsten

AU - Løes, Inger Marie

AU - He, Jin

AU - Pawlik, Timothy M.

AU - Kaczirek, Klaus

AU - Poultsides, George

AU - Lønning, Per Eystein

AU - Cameron, John L

AU - Mischinger, Hans Joerg

AU - Aucejo, Federico N.

AU - Kreis, Martin E.

AU - Wolfgang, Christopher

AU - Weiss, Matthew J

PY - 2019/6/1

Y1 - 2019/6/1

N2 - OBJECTIVE: To evaluate the changing impact of genetic and clinicopathologic factors on conditional overall survival (CS) over time in patients with resectable colorectal liver metastasis. BACKGROUND: CS estimates account for the changing likelihood of survival over time and may reveal the changing impact of prognostic factors as time accrues from the date of surgery. METHODS: CS analysis was performed in 1099 patients of an international, multi-institutional cohort. Three-year CS (CS3) estimates at the "xth" year after surgery were calculated as follows: CS3 = CS (x + 3)/CS (x). The standardized difference (d) between CS3 rates was used to estimate the changing prognostic power of selected variables over time. A d < 0.1 indicated very small differences between groups, 0.1 ≤ d < 0.3 indicated small differences, 0.3 ≤ d < 0.5 indicated moderate differences, and d ≥ 0.5 indicated strong differences. RESULTS: According to OS estimates calculated at the time of surgery, the presence of BRAF and KRAS mutations, R1 margin status, resected extrahepatic disease, patient age, primary tumor lymph node metastasis, tumor number, and carcinoembryonic antigen levels independently predicted worse survival. However, when temporal changes in the prognostic impact of these variables were considered using CS3 estimates, BRAF mutation dominated prognosis during the first year (d = 0.48), whereas surgeon-related variables (ie, surgical margin and resected extrahepatic disease) determined prognosis thereafter (d ≥ 0.5). Traditional clinicopathologic factors affected survival constantly, but only to a moderate degree (0.3 ≤ d < 0.5). CONCLUSIONS: The impact of genetic, surgery-related, and clinicopathologic factors on OS and CS3 changed dramatically over time. Specifically, BRAF mutation status dominated prognosis in the first year, whereas positive surgical margins and resected extrahepatic disease determined prognosis thereafter.

AB - OBJECTIVE: To evaluate the changing impact of genetic and clinicopathologic factors on conditional overall survival (CS) over time in patients with resectable colorectal liver metastasis. BACKGROUND: CS estimates account for the changing likelihood of survival over time and may reveal the changing impact of prognostic factors as time accrues from the date of surgery. METHODS: CS analysis was performed in 1099 patients of an international, multi-institutional cohort. Three-year CS (CS3) estimates at the "xth" year after surgery were calculated as follows: CS3 = CS (x + 3)/CS (x). The standardized difference (d) between CS3 rates was used to estimate the changing prognostic power of selected variables over time. A d < 0.1 indicated very small differences between groups, 0.1 ≤ d < 0.3 indicated small differences, 0.3 ≤ d < 0.5 indicated moderate differences, and d ≥ 0.5 indicated strong differences. RESULTS: According to OS estimates calculated at the time of surgery, the presence of BRAF and KRAS mutations, R1 margin status, resected extrahepatic disease, patient age, primary tumor lymph node metastasis, tumor number, and carcinoembryonic antigen levels independently predicted worse survival. However, when temporal changes in the prognostic impact of these variables were considered using CS3 estimates, BRAF mutation dominated prognosis during the first year (d = 0.48), whereas surgeon-related variables (ie, surgical margin and resected extrahepatic disease) determined prognosis thereafter (d ≥ 0.5). Traditional clinicopathologic factors affected survival constantly, but only to a moderate degree (0.3 ≤ d < 0.5). CONCLUSIONS: The impact of genetic, surgery-related, and clinicopathologic factors on OS and CS3 changed dramatically over time. Specifically, BRAF mutation status dominated prognosis in the first year, whereas positive surgical margins and resected extrahepatic disease determined prognosis thereafter.

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