Blood flow changes in hepatocellular carcinoma after the administration of thalidomide assessed by reperfusion kinetics during microbubble infusion: preliminary results.
OBJECTIVE
We sought to investigate whether thalidomide is able to produce tumor vascular changes in patients with untreatable hepatocellular carcinoma (HCC) that can be detected using microbubble contrast agents.


METHODS
Eleven consecutive patients with untreatable HCC underwent contrast-enhanced ultrasound before and during thalidomide administration. Real-time destruction reperfusion kinetics was obtained from a representative HCC nodule and from the surrounding liver parenchyma during SonoVue infusion (Bracco, Milan, Italy) at a constant rate of 0.10 mL/s by using a syringe pump and modelized according to the mathematical function SI = A(1 - exp(-betat)) where the plateau signal intensity A reflects the percent blood volume, the time constant beta reflects the average speed of blood, and their product A*beta reflects the nutrient blood flow.


RESULTS
Size of the representative nodule reduced significantly 3 to 6 months after the start of thalidomide treatment. Before thalidomide administration A, beta, and A*beta of the index lesion were 44 +/- 60 LIU, 0.31 +/- 0.40 seconds and 8.1 +/- 11.8 LIU/s, respectively). A and A*beta reduced significantly after 15 days (26 +/- 50 LIU and 2.9 +/- 4.8 LIU/s, P < 0.01), 3 months (12 +/- 18 LIU, and 4.3 +/- 7.7 LIU/s, P < 0.01), and 6 months (13 +/- 23 LIU and 2.4 +/- 3.7 LIU/s, P < 0.05) of treatment. No statistically significant changes of the exponential time constant beta were observed, nor changes of A, beta and A*beta in the liver parenchyma.


CONCLUSIONS
Contrast-enhanced ultrasound can be used effectively to evaluate changes in perfusion parameters of HCC nodules during thalidomide administration.
Bertolotto
Michele
M
UCO di Radiologia, Università di Trieste, Ospedale di Cattinara, Italy. bertolot@units.it
Pozzato
Gabriele
G
Crocè
Lory Saveria
LS
Nascimben
Fabiana
F
Gasparini
Cristiana
C
Cova
Maria Assunta
MA
Tiribelli
Claudio
C
D000368:Aged; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000000981:diagnostic imaging / Q000188:drug therapy*; D003287:Contrast Media; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008113:Liver Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy*; D008297:Male; D045423:Microbubbles; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D010743:Phospholipids; D018709:Statistics, Nonparametric; D013459:Sulfur Hexafluoride; D016019:Survival Analysis; D013792:Thalidomide / Q000627:therapeutic use*; D016896:Treatment Outcome; D018084:Ultrasonography, Interventional
D020533:Angiogenesis Inhibitors; D003287:Contrast Media; D010743:Phospholipids; C420843:contrast agent BR1; D013792:Thalidomide; D013459:Sulfur Hexafluoride