Regional chemotherapy for unresectable primary liver cancer: results of a phase II clinical trial and assessment of DCE-MRI as a biomarker of survival.
BACKGROUND
This study reports the results of hepatic arterial infusion (HAI) with floxuridine (FUDR) and dexamethasone (dex) in patients with unresectable intrahepatic cholangiocarcinoma (ICC) or hepatocellular carcinoma (HCC) and investigates dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) assessment of tumor vascularity as a biomarker of outcome.


METHODS
Thirty-four unresectable patients (26 ICC and eight HCC) were treated with HAI FUDR/dex. Radiologic dynamic and pharmacokinetic parameters related to tumor perfusion were analyzed and correlated with response and survival.


RESULTS
Partial responses were seen in 16 patients (47.1%); time to progression and response duration were 7.4 and 11.9 months, respectively. Median follow-up and median survival were 35 and 29.5 months, respectively; 2-year survival was 67%. DCE-MRI data showed that patients with pretreatment integrated area under the concentration curve of gadolinium contrast over 180 s (AUC 180) >34.2 mM.s had a longer median survival than those with AUC 180 <34 mM.s (35.1 versus 19.1 months, P = 0.002). Decreased volume transfer exchange between the vascular space and extracellular extravascular space (-DeltaK(trans)) and the corresponding rate constant (-Deltak(ep)) on the first post-treatment scan both predicted survival.


CONCLUSIONS
In patients with unresectable primary liver cancer, HAI therapy can be effective and safe. Pretreatment and early post-treatment changes in tumor perfusion characteristics may predict treatment outcome.
Jarnagin
W R
WR
Department of Surgery. Electronic address: jarnagiw@mskcc.org.
Schwartz
L H
LH
Department of Radiology.
Gultekin
D H
DH
Department of Radiology.
Gönen
M
M
Department of Epidemiology and Biostatistics.
Haviland
D
D
Department of Medical Oncology.
Shia
J
J
Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
D'Angelica
M
M
Department of Surgery.
Fong
Y
Y
Department of Surgery.
DeMatteo
R
R
Department of Surgery.
Tse
A
A
Department of Medical Oncology.
Blumgart
L H
LH
Department of Surgery.
Kemeny
N
N
Department of Medical Oncology.
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D019540:Area Under Curve; D001650:Bile Duct Neoplasms / Q000188:drug therapy; D001653:Bile Ducts, Intrahepatic / Q000473:pathology; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy; D010478:Chemotherapy, Cancer, Regional Perfusion; D018281:Cholangiocarcinoma / Q000188:drug therapy; D003907:Dexamethasone / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D005467:Floxuridine / Q000008:administration & dosage; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000401:mortality*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D016019:Survival Analysis; D016896:Treatment Outcome
D005467:Floxuridine; D003907:Dexamethasone