Date: Saturday, April 29, 2017
Session Time: 5:30pm-7:30pm
Presentation Time: 5:30pm-7:30pm
Location: Hall D1
Purpose: TGFβ signaling is an integral pathway in hepatocellular carcinoma (HCC) metastasis. In this study, we monitored TGFβ levels and imaging response in HCC patients undergoing chemoembolization (DEB-TACE) as a bridge to liver transplantation.
Methods: Liver transplant candidate HCC patients undergoing DEB-TACE were prospectively enrolled. Blood was collected before/after DEB-TACE (100-300[micro]m LC Beads with 50-75mg doxorubicin) and at 30 day follow-up. Plasma cytokine levels were quantified by Multiplex assays. Tumor response to DEB-TACE was determined using mRECIST imaging criteria.
Results: Patients consisted of 85% Hepatitis C, 55% male, with average MELD at DEB-TACE of 10.25 points. Analysis was performed on 37 patients, including 18 de novo, 16 previously embolized, and 3 patients monitored through consecutive DEB-TACE cycles. Treatment responses were: disease progression (DP) – 10%, stable disease (SD) – 35%, partial response (PR) – 5%, complete response (CR) – 50%. Embolization history and mRECIST response dramatically influenced follow-up TGFβ levels. TGFβ was decreased in de novo compared to prior DEB-TACE history (899 vs. 1674 pg/mL). CR/PR tumor response also associated with lower TGFβ levels compared to SD/DP (884 vs. 1799 pg/mL). No significant changes in TGFβ levels were present prior to DEB-TACE. Decreases in TGFβ mirrored reductions in several metastasis-linked factors, including IL-6 (4.3 vs. 17.8 pg/mL), MMP2 (82 vs. 152 ng/mL) and MMP3 (10.6 vs. 25.5 ng/mL). Pre-treatment lymphocyte counts were lower in patients with SD or DP compared to CR or PR (1.1 vs. 1.8 k/[mu]L) and in prior DEB-TACE vs. de novo patients (1.15 vs. 1.8 k/[mu]L). Finally, in patients monitored through consecutive DEB-TACE cycles, elevated TGFβ levels mirrored elevated CD33+CD14+HLA-DRNEG myeloid-derived suppressor cells.
Conclusions: Embolization history and unfavorable mRECIST scoring identified patients with elevated TGFβ after DEB-TACE. TGFβ levels are linked with HCC progression and metastasis as well as decreased anti-tumor immune responses. A biomarker panel capturing DEB-TACE response, immunoregulatory cell populations and mediators linked to HCC metastasis could help identify patients at high recurrence risk following liver transplantation.
CITATION INFORMATION: Thevenot P, Núñez K, Gonzalez-Rosario J, Sandow T, Alharbi A, Bokhari A, Wyczechowska D, Ochoa A, Cohen A. Effect of Embolization History and Tumor Treatment Response on Plasma TGFβ in HCC Patients Listed for Liver Transplantation. Am J Transplant. 2017;17 (suppl 3).
To cite this abstract in AMA style:Thevenot P, Núñez K, Gonzalez-Rosario J, Sandow T, Alharbi A, Bokhari A, Wyczechowska D, Ochoa A, Cohen A. Effect of Embolization History and Tumor Treatment Response on Plasma TGFβ in HCC Patients Listed for Liver Transplantation. [abstract]. Am J Transplant. 2017; 17 (suppl 3). https://atcmeetingabstracts.com/abstract/effect-of-embolization-history-and-tumor-treatment-response-on-plasma-tgf-in-hcc-patients-listed-for-liver-transplantation/. Accessed May 22, 2019.
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