Early Response to Anti-Tumoral Treatment in Hepatocellular Carcinoma – Can Quantitative Contrast-Enhanced Ultrasound Predict Outcome?

Abstract

Purpose: In order to detect an early response to anti-angiogenic therapy, this study aims at analyzing specific effects of a sorafenib-based regime on intra-tumoral D-CEUS flow parameters of patients with HCC.

Materials and Methods: Videos of the arterial phase were captured before initiation of a therapy with sorafenib and 1 and 3 months after (n = 9). Patients receiving a non-anti-angiogenic therapy (TACE, n = 10) served as a comparison group. Cross-sectional imaging was performed at the same time points and patients were followed up for 1 year.

Results: In the responder group (RE), the absolute (percentage) TTP was 11.28 s ± 2.03 s (1.00) before treatment, 13.60 s ± 1.52 s (1.53 ± 0.08) after one month (p = 0.0405), and 16.17 s ± 2.35 s (1.46 ± 0.07) after three months of treatment (p = 0.0071). The TTP increased significantly in the RE group as early as 1 month after initiation of sorafenib compared to the non-responder group. There were no significant differences in the non-responder group or between the NR and the TACE group at any time point. D-CEUS values from all sorafenib-treated patients showed good accordance with RECICL (response evaluation criteria in cancer of the liver) criteria (R² = 0.7154, p = 0.0001).

Conclusions: Quantitative CEUS reveals variations of dynamic parameters of blood flow during anti-tumoral therapy in liver cancer patients. Further investigations and clinical trails have to confirm that the TTP is a promising parameter in the prediction of early response to sorafenib-based therapy.

Zusammenfassung

Ziel: Diese Studie versucht, Hinweise für ein frühes Therapieansprechen zu erhalten, indem die Einflüsse der dynamischen Flussparameter von D-CEUS auf eine anti-angiogenetische Therapie mit Sorafenib bei HCC analysieren werden.

Material und Methoden: Es wurden die Videosequenzen der arteriellen Anflutungsphase jeweils vor und 1 bzw. 3 Monate nach Beginn der Therapie mit Sorafenib (n = 9) aufgezeichnet. Als Vergleich dienten Patienten, die eine nicht anti-angiogenetische Therapie (TACE, n = 10) erhielten. Schnittbildgebung und eine Beobachtung über ein Jahr erfolgten.

Ergebnisse: In der Responder-Gruppe (RE) ergab sich ein absoluter (prozentualer) Anstieg der TPP von 11,28 s ± 2,03 s (1,00) auf 13,60 s ± 1,52 s (1,53 ± 0,08) nach 1 Monat (p = 0,0405) und 16,17 s ± 2,35 s (1,46 ± 0,07) nach 3 Monaten Therapie (p = 0,0071). Die TTP stiegt in der RE-Gruppe, im Gegensatz zur Non-Responder(NR)-Gruppe, innerhalb eines Monats nach Start der Therapie mit Sorafenib signifikant an. Weiterhin ergaben sich keine signifikanten Unterschiede in der Non-Responder-Gruppe oder zwischen der NR- und der TACE-Gruppe zu den Beobachtungszeitpunkten. Die D-CEUS-Werte von allen Sorafenib-Patienten zeigten eine gute Übereinstimmung mit den RECICL(Response Evaluation Criteria in Cancer of the Liver)-Kriterien (R² = 0,7154, p = 0,0001).

Schlussfolgerung: Die quantitative CEUS zeigt Veränderungen der dynamischen Durchblutungsparameter während unterschiedlichen Therapieformen in Patienten mit hepatozellulären Karzinomen. Weitere Untersuchungen und klinische Studien müssen zeigen, ob die TTP ein vielversprechender Parameter für die Vorhersage des frühen Ansprechens auf eine Sorafenib-Therapie sein kann.

Key words

abdomen - angiogenesis - microbubbles - ultrasound - tumor

^* These authors contributed equally to the study.

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