{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T00:00:43Z","timestamp":1790899243130,"version":"4.1.0"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,7,6]],"date-time":"2023-07-06T00:00:00Z","timestamp":1688601600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec><jats:title>Introduction and aim<\/jats:title><jats:p>Intrahepatic cholangiocarcinoma (iCCA) is a disease characterized by rarity, heterogeneity, and high mortality, where surgical resection is often not possible. Nowadays, due to the recent introduction of new therapeutic options such as trans-arterial radioembolization (TARE), it is increasingly important to define the role of morphofunctional imaging methods for the prognostic stratification of patients affected by iCCA. The aim of the study was to verify the prognostic value of morphofunctional imaging methods at the baseline in patients with inoperable iCCA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In total, 45 patients with iCCA were sent to our center between January 2016 and March 2021 for being evaluated to be treated with TARE. All of them underwent both [18F]-FDG-PET\/CT and contrast-enhanced CT (ceCT) in a single procedure and were included in our study. The inclusion criteria were as follows: a diagnosis of inoperable iCCA; both [18F]-FDG-PET\/CT and ceCT scans; and washout from therapy for at least 2 months before baseline [18F]-FDG-PET\/CT and ceCT scans. Both clinical and laboratory data and baseline imaging data (ceCT and [18F]-FDG-PET\/CT) were collected. In particular, regarding clinical and laboratory data, we collected overall survival (OS), gender, age, prior therapies, liver function indices, and tumor markers. Regarding ceCT, we collected TNM staging, lesion diameter, volume, vascularization, and presence of intravascular necrosis. Regarding [18F]-FDG-PET\/CT, we collected TNM staging, Standard-Uptake-Value max (SUVmax), Metabolic-Tumor-Volume (MTV), and Total-Lesion-Glycolysis (TLG=MTV<jats:sup>*<\/jats:sup>lesions SUVmean). Philips-Vue-PACS software was used, setting hepatic SUVmean as TLG threshold.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A statistically significant correlation was found between some examined parameters at morphofunctional investigations at the baseline and OS. [18F]-FDG-PET\/CT parameters statistically correlated with OS were the stage of disease greater than M0 (<jats:italic>p<\/jats:italic> = 0.037), major lesion SUVmax (<jats:italic>p<\/jats:italic> = 0.010), MTV (<jats:italic>p<\/jats:italic> \u2264 0.001), and TLG (<jats:italic>p<\/jats:italic> &amp;lt; 0.001). Other parameters at ceCT correlated with OS were the stage of disease greater than T2 (<jats:italic>p<\/jats:italic> = 0.038), maximum lesion diameter (<jats:italic>p<\/jats:italic> = 0.07), volume of the major lesion (<jats:italic>p<\/jats:italic> = 0.016), and total volume of lesions (<jats:italic>p<\/jats:italic> = 0. 009). Biochemical parameters correlated with OS were gamma glutamyl transferase (GGT, <jats:italic>p<\/jats:italic> = 0.014), alkaline phosphatase (ALP, <jats:italic>p<\/jats:italic> = 0.019), carcinoembryonic antigen (CEA, <jats:italic>p<\/jats:italic> = 0.004), and carbohydrate antigen 19-9 (CA 19-9, <jats:italic>p<\/jats:italic> &amp;lt; 0.001). From the parameters estimated by the multivariate model, we derived a four-variable score for OS combining nodal involvement and SUVmax at [18F]-FDG-PET\/CT, GGT, and CA 19-9 levels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Considering our data, performing integrated pre-therapy imaging is critical for the prognostic stratification of patients with iCCA.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmed.2023.1204717","type":"journal-article","created":{"date-parts":[[2023,7,6]],"date-time":"2023-07-06T17:01:43Z","timestamp":1688662903000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Prognostic value of integrated morphofunctional imaging methods in inoperable intrahepatic cholangiocarcinoma"],"prefix":"10.3389","volume":"10","author":[{"given":"Cristina","family":"Nanni","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Mosconi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentino","family":"Dragonetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Barakat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Fraccascia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Adriana","family":"Cocozza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Brocchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Palloni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandro","family":"Paccapelo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Brandi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Fanti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,7,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"873","DOI":"10.1093\/jnci\/djj234","article-title":"Impact of classification of hilar cholangiocarcinomas (Klatskin tumors) on the incidence of intra- and extrahepatic cholangiocarcinoma in the United States","volume":"98","author":"Welzel","year":"2006","journal-title":"J Natl Cancer Inst."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1215","DOI":"10.1053\/j.gastro.2013.10.013","article-title":"Pathogenesis, diagnosis, and management of cholangiocarcinoma","volume":"145","author":"Rizvi","year":"2013","journal-title":"Gastroenterology."},{"key":"B3","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1016\/j.bpg.2015.02.003","article-title":"Epidemiology of cholangiocarcinoma","volume":"29","author":"Bergquist","year":"2015","journal-title":"Best Pract Res Clin Gastroenterol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"512","DOI":"10.1038\/nrgastro.2011.131","article-title":"Clinical diagnosis and staging of cholangiocarcinoma","volume":"8","author":"Blechacz","year":"2011","journal-title":"Nat Rev Gastroenterol Hepatol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1055\/s-2004-828889","article-title":"The epidemiology of cholangiocarcinoma","volume":"24","author":"Shaib","year":"2004","journal-title":"Semin Liver Dis."},{"key":"B6","doi-asserted-by":"publisher","first-page":"472","DOI":"10.1016\/j.jhep.2003.11.030","article-title":"Rising incidence of intrahepatic cholangiocarcinoma in the United States: a true increase?","volume":"40","author":"Shaib","year":"2004","journal-title":"J Hepatol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1080\/13651820801992641","article-title":"Epidemiology, risk factors, and pathogenesis of cholangiocarcinoma","volume":"10","author":"Khan","year":"2008","journal-title":"HPB."},{"key":"B8","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1016\/j.cld.2007.11.003","article-title":"Cholangiocarcinoma","volume":"12","author":"Blechacz","year":"2008","journal-title":"Clin Liver Dis."},{"key":"B9","doi-asserted-by":"publisher","first-page":"669","DOI":"10.1111\/hpb.12441","article-title":"Intrahepatic cholangiocarcinoma: expert consensus statement","volume":"17","author":"Weber","year":"2015","journal-title":"HPB."},{"key":"B10","doi-asserted-by":"publisher","first-page":"3998","DOI":"10.1002\/cncr.29619","article-title":"Can hepatic resection provide a long-term cure for patients with intrahepatic cholangiocarcinoma?","volume":"121","author":"Spolverato","year":"2015","journal-title":"Cancer."},{"key":"B11","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/j.jhep.2006.03.009","article-title":"Impact of integrated positron emission tomography and computed tomography on staging and management of gallbladder cancer and cholangiocarcinoma","volume":"45","author":"Petrowsky","year":"2006","journal-title":"J Hepatol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1492","DOI":"10.1007\/s00261-015-0352-9","article-title":"Intratumoral artery on contrast-enhanced computed tomography imaging: differentiating intrahepatic cholangiocarcinoma from poorly differentiated hepatocellular carcinoma","volume":"40","author":"Tsunematsu","year":"2015","journal-title":"Abdom Imaging."},{"key":"B13","doi-asserted-by":"publisher","first-page":"670","DOI":"10.1097\/00004728-199909000-00004","article-title":"Intrahepatic peripheral cholangiocarcinoma: comparison of dynamic CT and dynamic MRI","volume":"23","author":"Zhang","year":"1999","journal-title":"J Comput Assist Tomogr."},{"key":"B14","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1080\/13651820801992617","article-title":"Staging cholangiocarcinoma by imaging studies","volume":"10","author":"Vilgrain","year":"2008","journal-title":"HPB."},{"key":"B15","doi-asserted-by":"publisher","first-page":"850","DOI":"10.1007\/s11605-003-0029-5","article-title":"Patterns of regional lymph node involvement in intrahepatic cholangiocarcinoma of the left lobe","volume":"7","author":"Okami","year":"2003","journal-title":"J Gastrointest Surg."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1193","DOI":"10.1007\/s00261-014-0167-0","article-title":"Correlation of CT patterns of primary intrahepatic cholangiocarcinoma at the time of presentation with the metastatic spread and clinical outcomes: retrospective study of 92 patients","volume":"39","author":"Baheti","year":"2014","journal-title":"Abdom Imaging."},{"key":"B17","doi-asserted-by":"publisher","first-page":"406","DOI":"10.1016\/j.crad.2018.12.016","article-title":"Differentiating between hepatocellular carcinoma and intrahepatic cholangiocarcinoma using contrast-enhanced MRI features: a systematic review and meta-analysis","volume":"74","author":"You","year":"2019","journal-title":"Clin Radiol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"247693","DOI":"10.1155\/2014\/247693","article-title":"Diagnostic accuracy of fluorine-18-fluorodeoxyglucose positron emission tomography in the evaluation of the primary tumor in patients with cholangiocarcinoma: a meta-analysis","volume":"2014","author":"Annunziata","year":"2014","journal-title":"Biomed Res Int."},{"key":"B19","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/j.jamcollsurg.2007.07.002","article-title":"18F-fluorodeoxyglucose positron emission tomography influences management decisions in patients with biliary cancer","volume":"206","author":"Corvera","year":"2008","journal-title":"J Am Coll Surg."},{"key":"B20","doi-asserted-by":"publisher","first-page":"759","DOI":"10.1111\/j.1440-1746.2007.05173.x","article-title":"Usefulness of 18F-fluorodeoxyglucose positron emission tomography in differential diagnosis and staging of cholangiocarcinomas","volume":"23","author":"Moon","year":"2008","journal-title":"J Gastroenterol Hepatol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"823","DOI":"10.1007\/s00268-017-4192-3","article-title":"Diagnostic and prognostic role of 18-FDG PET\/CT in the management of resectable biliary tract cancer","volume":"42","author":"Ma","year":"2018","journal-title":"World J Surg."},{"key":"B22","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1186\/s12967-018-1475-x","article-title":"Preoperative metabolic tumor volume of intrahepatic cholangiocarcinoma measured by 18F-FDG-PET is associated with the KRAS mutation status and prognosis","volume":"16","author":"Ikeno","year":"2018","journal-title":"J Transl Med."},{"key":"B23","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1007\/s00259-014-2961-x","article-title":"FDG PET\/CT: EANM procedure guidelines for tumour imaging: version 20","volume":"42","author":"Boellaard","year":"2015","journal-title":"Eur J Nucl Med Mol Imaging."},{"key":"B24","doi-asserted-by":"publisher","first-page":"2493","DOI":"10.1109\/NSSMIC.2004.1462761","article-title":"A fully 3D iterative image reconstruction algorithm incorporating data corrections","volume":"4","author":"Iatrou","year":"2004","journal-title":"IEEE Symposium Conf. Rec. Nucl. Sci"},{"key":"B25","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1038\/bjc.2016.191","article-title":"Yttrium-90 radioembolization for unresectable\/recurrent intrahepatic cholangiocarcinoma: a survival, efficacy and safety study","volume":"115","author":"Mosconi","year":"2016","journal-title":"Br J Cancer."},{"key":"B26","doi-asserted-by":"publisher","first-page":"1036","DOI":"10.1111\/liv.12574","article-title":"Yttrium-90 radioembolization vs sorafenib for intermediate-locally advanced hepatocellular carcinoma: a cohort study with propensity score analysis","volume":"35","author":"Gramenzi","year":"2015","journal-title":"Liver Int."},{"key":"B27","doi-asserted-by":"publisher","first-page":"498","DOI":"10.1007\/s00330-016-4386-3","article-title":"Mass-forming intrahepatic cholangiocarcinoma: enhancement patterns in the arterial phase of dynamic hepatic CT - correlation with clinicopathological findings","volume":"27","author":"Fujita","year":"2017","journal-title":"Eur Radiol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1080\/14737140.2022.1999809","article-title":"Surgical management of intrahepatic cholangiocarcinoma","volume":"22","author":"Hewitt","year":"2022","journal-title":"Expert Rev Anticancer Ther."},{"key":"B29","doi-asserted-by":"publisher","first-page":"101696","DOI":"10.1016\/j.suronc.2021.101696","article-title":"Arterial enhancement pattern predicts survival in patients with resectable and unresectable intrahepatic cholangiocarcinoma","volume":"40","author":"Panettieri","year":"2022","journal-title":"Surg Oncol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1016\/j.hpb.2021.06.424","article-title":"Prognostic impact of tumor vascularity on CT in resectable intrahepatic cholangiocarcinoma","volume":"24","author":"Park","year":"2022","journal-title":"HPB."},{"key":"B31","doi-asserted-by":"publisher","first-page":"1341","DOI":"10.1016\/j.hpb.2022.02.004","article-title":"Machine learning radiomics can predict early liver recurrence after resection of intrahepatic cholangiocarcinoma","volume":"24","author":"Jolissaint","year":"2022","journal-title":"HPB."},{"key":"B32","doi-asserted-by":"publisher","first-page":"4534","DOI":"10.1007\/s00330-020-06795-9","article-title":"Radiomics of cholangiocarcinoma on pretreatment CT can identify patients who would best respond to radioembolisation","volume":"30","author":"Mosconi","year":"2020","journal-title":"Eur Radiol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"1029","DOI":"10.1053\/jhep.2001.23912","article-title":"Positron emission tomography with [(18)F]fluoro-2-deoxy-D-glucose for diagnosis and staging of bile duct cancer","volume":"33","author":"Kluge","year":"2001","journal-title":"Hepatology."},{"key":"B34","doi-asserted-by":"publisher","first-page":"1047","DOI":"10.1007\/s00259-002-0852-z","article-title":"Clinical role of (18)F-FDG PET for initial staging of patients with extrahepatic bile duct cancer","volume":"29","author":"Kato","year":"2002","journal-title":"Eur J Nucl Med Mol Imaging."},{"key":"B35","doi-asserted-by":"publisher","first-page":"1277","DOI":"10.1097\/00006231-200112000-00002","article-title":"in the diagnosis of hilar cholangiocarcinoma","volume":"22","author":"Fritscher-Ravens","year":"2001","journal-title":"Nucl Med Commun."},{"key":"B36","doi-asserted-by":"publisher","first-page":"v28","DOI":"10.1093\/annonc\/mdw324","article-title":"ESMO Guidelines Committee. Biliary cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up","volume":"27","author":"Valle","year":"2016","journal-title":"Ann Oncol."}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2023.1204717\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,6]],"date-time":"2023-07-06T17:01:45Z","timestamp":1688662905000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2023.1204717\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,6]]},"references-count":36,"alternative-id":["10.3389\/fmed.2023.1204717"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2023.1204717","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,6]]},"article-number":"1204717"}}