Savic, Lynn J., Chapiro, Julius, Funai, Eliot, Bousabarah, Khaled, Schobert, Isabel T., Isufi, Edvin, Geschwind, Jean-Francois H., Stark, Sophie, He, Ping, Rudek, Michelle A., Lozada, Juan Carlos Perez, Ayyagari, Rajasekhara, Pollak, Jeffrey and Schlachter, Todd . Prospective study of Lipiodol distribution as an imaging marker for doxorubicin pharmacokinetics during conventional transarterial chemoembolization of liver malignancies. Eur. Radiol.. NEW YORK: SPRINGER. ISSN 1432-1084

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Abstract

Objectives To evaluate the prognostic potential of Lipiodol distribution for the pharmacokinetic (PK) profiles of doxorubicin (DOX) and doxorubicinol (DOXOL) after conventional transarterial chemoembolization (cTACE). Methods This prospective clinical trial (: NCT02753881) included 30 consecutive participants with liver malignancies treated with cTACE (5/2016-10/2018) using 50 mg DOX/10 mg mitomycin C emulsified 1:2 with ethiodized oil (Lipiodol). Peripheral blood was sampled at 10 timepoints for standard non-compartmental analysis of peak concentrations (C-max) and area under the curve (AUC) with dose normalization (DN). Imaging markers included Lipiodol distribution on post-cTACE CT for patient stratification into 1 segment (n = 10), >= 2 segments (n = 10), and lobar cTACE (n = 10), and baseline enhancing tumor volume (ETV). Adverse events (AEs) and tumor response on MRI were recorded 3-4 weeks post-cTACE. Statistics included repeated measurement ANOVA (RM-ANOVA), Mann-Whitney, Kruskal-Wallis, Fisher's exact test, and Pearson correlation. Results Hepatocellular (n = 26), cholangiocarcinoma (n = 1), and neuroendocrine metastases (n = 3) were included. Stratified according to Lipiodol distribution, DOX-C(max)increased from 1 segment (DOX-C-max, 83.94 +/- 75.09 ng/mL; DN-DOX-C-max, 2.67 +/- 2.02 ng/mL/mg) to >= 2 segments (DOX-C-max, 139.66 +/- 117.73 ng/mL; DN-DOX-C-max, 3.68 +/- 4.20 ng/mL/mg) to lobar distribution (DOX-C-max, 334.35 +/- 215.18 ng/mL; DN-DOX-C-max, 7.11 +/- 4.24 ng/mL/mg;p = 0.036). While differences in DN-DOX-AUC remained insignificant, RM-ANOVA revealed significant separation of time concentration curves for DOX (p = 0.023) and DOXOL (p = 0.041) comparing 1, >= 2 segments, and lobar cTACE. Additional indicators of higher DN-DOX-C(max)were high ETV (p = 0.047) and Child-Pugh B (p = 0.009). High ETV and tumoral Lipiodol coverage also correlated with tumor response. AE occurred less frequently after segmental cTACE. Conclusions This prospective clinical trial provides updated PK data revealing Lipiodol distribution as an imaging marker predictive of DOX-C(max)and tumor response after cTACE in liver cancer.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Savic, Lynn J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chapiro, JuliusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Funai, EliotUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bousabarah, KhaledUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schobert, Isabel T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Isufi, EdvinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Geschwind, Jean-Francois H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stark, SophieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
He, PingUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rudek, Michelle A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lozada, Juan Carlos PerezUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ayyagari, RajasekharaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pollak, JeffreyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schlachter, ToddUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-314872
DOI: 10.1007/s00330-020-07380-w
Journal or Publication Title: Eur. Radiol.
Publisher: SPRINGER
Place of Publication: NEW YORK
ISSN: 1432-1084
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
TRANSCATHETER ARTERIAL CHEMOEMBOLIZATION; UNRESECTABLE HEPATOCELLULAR-CARCINOMA; BEAM COMPUTED-TOMOGRAPHY; DRUG-ELUTING BEADS; EFFICACY; SAFETY; EMBOLIZATION; CHEMOTHERAPY; METABOLITE; DEPOSITIONMultiple languages
Radiology, Nuclear Medicine & Medical ImagingMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/31487

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