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Preoperative metabolic tumor volume of intrahepatic cholangiocarcinoma measured by (18)F-FDG-PET is associated with the KRAS mutation status and prognosis

BACKGROUND: Surgical resection remains the mainstay of curative treatment for intrahepatic cholangiocarcinoma (ICC). Prognosis after surgery is unsatisfactory despite improvements in treatment and post-operative clinical management. Despite developments in the molecular profiling of ICC, the preoper...

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Autores principales: Ikeno, Yoshinobu, Seo, Satoru, Iwaisako, Keiko, Yoh, Tomoaki, Nakamoto, Yuji, Fuji, Hiroaki, Taura, Kojiro, Okajima, Hideaki, Kaido, Toshimi, Sakaguchi, Shimon, Uemoto, Shinji
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5896043/
https://www.ncbi.nlm.nih.gov/pubmed/29642912
http://dx.doi.org/10.1186/s12967-018-1475-x
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author Ikeno, Yoshinobu
Seo, Satoru
Iwaisako, Keiko
Yoh, Tomoaki
Nakamoto, Yuji
Fuji, Hiroaki
Taura, Kojiro
Okajima, Hideaki
Kaido, Toshimi
Sakaguchi, Shimon
Uemoto, Shinji
author_facet Ikeno, Yoshinobu
Seo, Satoru
Iwaisako, Keiko
Yoh, Tomoaki
Nakamoto, Yuji
Fuji, Hiroaki
Taura, Kojiro
Okajima, Hideaki
Kaido, Toshimi
Sakaguchi, Shimon
Uemoto, Shinji
author_sort Ikeno, Yoshinobu
collection PubMed
description BACKGROUND: Surgical resection remains the mainstay of curative treatment for intrahepatic cholangiocarcinoma (ICC). Prognosis after surgery is unsatisfactory despite improvements in treatment and post-operative clinical management. Despite developments in the molecular profiling of ICC, the preoperative prediction of prognosis remains a challenge. This study aimed to identify clinical prognostic indicators by investigating the molecular profiles of ICC and evaluating the preoperative imaging data of (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG-PET). METHODS: A retrospective analysis was performed on 50 consecutive patients with ICC who underwent curative hepatectomy after (18)F-FDG-PET examination. To evaluate the molecular profiles of ICC, KRAS mutation status was assessed in resected specimens. For the assessment of glucose uptake, we observed the expression of glucose transporter-1 (GLUT-1) by immunohistochemistry. The data of (18)F-FDG-PET were re-evaluated as follows: maximum standardized uptake value, metabolic tumor volume (MTV), and total lesion glycolysis (TLG). Cut-off values were determined using receiver operating characteristic (ROC) curve analysis. Cumulative overall survival (OS) was analyzed using the Kaplan–Meier analysis. RESULTS: Overall, 16 (32.0%) patients had mutations in KRAS. Patients with mutated KRAS exhibited shorter OS than those with wild-type KRAS (5-year OS, 0% vs. 35.1%, P < 0.001). GLUT-1 expression was significantly higher in tumors with mutated KRAS than in tumors with wild-type KRAS (median, 4.0 vs. 1.0, P < 0.001). Survival was significantly different when stratified by expression of GLUT-1 (5-year OS, 0% vs. 46.5%, P <0.001). Among the (18)F-FDG-PET parameters, the MTV and TLG were significantly higher in the mutated KRAS group than in the wild-type KRAS group (P = 0.013 and P = 0.026, respectively). ROC curve analysis revealed a cut-off value of 38 for the MTV, with the highest accuracy (area under the curve = 0.789; 95% confidence interval, 0.581–0.902) for predicting KRAS mutation. This cut-off value permitted stratification of OS (high vs. low: 5-year OS, 13.1% vs. 36.7%, P = 0.008). CONCLUSIONS: High MTV is associated with KRAS mutation and poor postoperative outcomes in patients with ICC, suggesting that the MTV of ICC measured by (18)F-FDG-PET may provide useful information for tumor molecular profiles and prognosis. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12967-018-1475-x) contains supplementary material, which is available to authorized users.
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spelling pubmed-58960432018-04-12 Preoperative metabolic tumor volume of intrahepatic cholangiocarcinoma measured by (18)F-FDG-PET is associated with the KRAS mutation status and prognosis Ikeno, Yoshinobu Seo, Satoru Iwaisako, Keiko Yoh, Tomoaki Nakamoto, Yuji Fuji, Hiroaki Taura, Kojiro Okajima, Hideaki Kaido, Toshimi Sakaguchi, Shimon Uemoto, Shinji J Transl Med Research BACKGROUND: Surgical resection remains the mainstay of curative treatment for intrahepatic cholangiocarcinoma (ICC). Prognosis after surgery is unsatisfactory despite improvements in treatment and post-operative clinical management. Despite developments in the molecular profiling of ICC, the preoperative prediction of prognosis remains a challenge. This study aimed to identify clinical prognostic indicators by investigating the molecular profiles of ICC and evaluating the preoperative imaging data of (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG-PET). METHODS: A retrospective analysis was performed on 50 consecutive patients with ICC who underwent curative hepatectomy after (18)F-FDG-PET examination. To evaluate the molecular profiles of ICC, KRAS mutation status was assessed in resected specimens. For the assessment of glucose uptake, we observed the expression of glucose transporter-1 (GLUT-1) by immunohistochemistry. The data of (18)F-FDG-PET were re-evaluated as follows: maximum standardized uptake value, metabolic tumor volume (MTV), and total lesion glycolysis (TLG). Cut-off values were determined using receiver operating characteristic (ROC) curve analysis. Cumulative overall survival (OS) was analyzed using the Kaplan–Meier analysis. RESULTS: Overall, 16 (32.0%) patients had mutations in KRAS. Patients with mutated KRAS exhibited shorter OS than those with wild-type KRAS (5-year OS, 0% vs. 35.1%, P < 0.001). GLUT-1 expression was significantly higher in tumors with mutated KRAS than in tumors with wild-type KRAS (median, 4.0 vs. 1.0, P < 0.001). Survival was significantly different when stratified by expression of GLUT-1 (5-year OS, 0% vs. 46.5%, P <0.001). Among the (18)F-FDG-PET parameters, the MTV and TLG were significantly higher in the mutated KRAS group than in the wild-type KRAS group (P = 0.013 and P = 0.026, respectively). ROC curve analysis revealed a cut-off value of 38 for the MTV, with the highest accuracy (area under the curve = 0.789; 95% confidence interval, 0.581–0.902) for predicting KRAS mutation. This cut-off value permitted stratification of OS (high vs. low: 5-year OS, 13.1% vs. 36.7%, P = 0.008). CONCLUSIONS: High MTV is associated with KRAS mutation and poor postoperative outcomes in patients with ICC, suggesting that the MTV of ICC measured by (18)F-FDG-PET may provide useful information for tumor molecular profiles and prognosis. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12967-018-1475-x) contains supplementary material, which is available to authorized users. BioMed Central 2018-04-11 /pmc/articles/PMC5896043/ /pubmed/29642912 http://dx.doi.org/10.1186/s12967-018-1475-x Text en © The Author(s) 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Ikeno, Yoshinobu
Seo, Satoru
Iwaisako, Keiko
Yoh, Tomoaki
Nakamoto, Yuji
Fuji, Hiroaki
Taura, Kojiro
Okajima, Hideaki
Kaido, Toshimi
Sakaguchi, Shimon
Uemoto, Shinji
Preoperative metabolic tumor volume of intrahepatic cholangiocarcinoma measured by (18)F-FDG-PET is associated with the KRAS mutation status and prognosis
title Preoperative metabolic tumor volume of intrahepatic cholangiocarcinoma measured by (18)F-FDG-PET is associated with the KRAS mutation status and prognosis
title_full Preoperative metabolic tumor volume of intrahepatic cholangiocarcinoma measured by (18)F-FDG-PET is associated with the KRAS mutation status and prognosis
title_fullStr Preoperative metabolic tumor volume of intrahepatic cholangiocarcinoma measured by (18)F-FDG-PET is associated with the KRAS mutation status and prognosis
title_full_unstemmed Preoperative metabolic tumor volume of intrahepatic cholangiocarcinoma measured by (18)F-FDG-PET is associated with the KRAS mutation status and prognosis
title_short Preoperative metabolic tumor volume of intrahepatic cholangiocarcinoma measured by (18)F-FDG-PET is associated with the KRAS mutation status and prognosis
title_sort preoperative metabolic tumor volume of intrahepatic cholangiocarcinoma measured by (18)f-fdg-pet is associated with the kras mutation status and prognosis
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5896043/
https://www.ncbi.nlm.nih.gov/pubmed/29642912
http://dx.doi.org/10.1186/s12967-018-1475-x
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