Prediction of Protumorigenic Effects after Image-Guided Radiofrequency Ablation of Hepatocellular Carcinoma Using Biomarkers

Matthias Stechele; Moritz Wildgruber; Aurelia Markezana; Sophia Kästle; Elif Öcal; Melanie A. Kimm; Marianna Alunni-Fabbroni; Mor Paldor; Liao Haixing; Lukas Salvermoser; Maciej Pech; Maciej Powerski; Eithan Galun; Jens Ricke; Shraga Nahum Goldberg

doi:10.1016/j.jvir.2022.11.024

Prediction of Protumorigenic Effects after Image-Guided Radiofrequency Ablation of Hepatocellular Carcinoma Using Biomarkers

Matthias Stechele^*, Moritz Wildgruber, Aurelia Markezana, Sophia Kästle, Elif Öcal, Melanie A. Kimm, Marianna Alunni-Fabbroni, Mor Paldor, Liao Haixing, Lukas Salvermoser, Maciej Pech, Maciej Powerski, Eithan Galun, Jens Ricke, Shraga Nahum Goldberg

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

2 Scopus citations

Abstract

Purpose: To perform radiofrequency (RF) ablation of hepatocellular carcinoma (HCC) and to assess serological and histopathological markers of tumorigenesis in distant untreated tumors to determine whether these were associated with unfavorable outcomes such as early relapse and increased biological aggressiveness. Materials and Methods: The study cohort comprised 13 patients from a prospective single-arm study. All patients underwent 2 ablation sessions of multifocal HCC nodules 14 days apart. Core biopsy samples of untreated tumors were acquired at baseline and at the time of the second ablation session. Samples were stained immunohistochemically with Ki-67 (proliferation) and CD34 (microvasculature). Blood plasma was obtained at baseline and 2 days after the initial ablation session and analyzed for hepatocyte growth factor (HGF), vascular endothelial growth factor C, and angiopoietin-2 using an enzyme-linked immunosorbent assay. The clinical follow-up period ranged from 7 to 25 months. Patients were stratified as responders (complete remission or limited and delayed recurrence at >6 months; n = 6) or nonresponders (any recurrence within 6 months or >3 new tumors or any new tumor of >3 cm thereafter; n = 7). Results: In 3 of 7 nonresponders, the Ki-67 index markedly increased in untreated tumors, whereas Ki-67 was stable in all responders. Microvascular density strongly increased in a single nonresponder only. HGF and angiopoietin-2 increased by >30% in 3 of 7 and 4 of 7 nonresponders, respectively, whereas they were stable or decreased in responders. Overall, ≥2 biomarkers were elevated in 6 of 7 (85.7%) nonresponders, whereas 4 of 6 responders demonstrated no increased biomarker and 2 patients demonstrated increase in 1 biomarker only (P = .002). Conclusions: RF ablation of HCC can produce protumorigenic factors that induce effects in distant untreated tumors. These may potentially function as biomarkers of clinical outcome.

Original language	American English
Journal	Journal of Vascular and Interventional Radiology
DOIs	https://doi.org/10.1016/j.jvir.2022.11.024
State	Accepted/In press - 2023
Externally published	Yes

Bibliographical note

Funding Information:
M.S. reports a travel grant from Rolf W. Guenther Foundation. M.W. is on the advisory board for iThera Medical Munich and receives lecture fees from Bayer Consumer Health. L.S. received grants from Deutsche Forschungsgesellschaft and Walter-Benjamin Program. S.N.G. reports grant support to institution from the Israel Science Foundation (904-2020), receives consulting fees from Cambridge Interventional and Xact Medical (to institution), and reports a travel grant from Rolf W. Guenther Foundation. None of the other authors have identified a conflict of interest.

Publisher Copyright:
© 2022 SIR

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10.1016/j.jvir.2022.11.024

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Stechele, M., Wildgruber, M., Markezana, A., Kästle, S., Öcal, E., Kimm, M. A., Alunni-Fabbroni, M., Paldor, M., Haixing, L., Salvermoser, L., Pech, M., Powerski, M., Galun, E., Ricke, J., & Goldberg, S. N. (Accepted/In press). Prediction of Protumorigenic Effects after Image-Guided Radiofrequency Ablation of Hepatocellular Carcinoma Using Biomarkers. Journal of Vascular and Interventional Radiology. https://doi.org/10.1016/j.jvir.2022.11.024

@article{b6490d6569f8437ea8b18216103927ca,

title = "Prediction of Protumorigenic Effects after Image-Guided Radiofrequency Ablation of Hepatocellular Carcinoma Using Biomarkers",

abstract = "Purpose: To perform radiofrequency (RF) ablation of hepatocellular carcinoma (HCC) and to assess serological and histopathological markers of tumorigenesis in distant untreated tumors to determine whether these were associated with unfavorable outcomes such as early relapse and increased biological aggressiveness. Materials and Methods: The study cohort comprised 13 patients from a prospective single-arm study. All patients underwent 2 ablation sessions of multifocal HCC nodules 14 days apart. Core biopsy samples of untreated tumors were acquired at baseline and at the time of the second ablation session. Samples were stained immunohistochemically with Ki-67 (proliferation) and CD34 (microvasculature). Blood plasma was obtained at baseline and 2 days after the initial ablation session and analyzed for hepatocyte growth factor (HGF), vascular endothelial growth factor C, and angiopoietin-2 using an enzyme-linked immunosorbent assay. The clinical follow-up period ranged from 7 to 25 months. Patients were stratified as responders (complete remission or limited and delayed recurrence at >6 months; n = 6) or nonresponders (any recurrence within 6 months or >3 new tumors or any new tumor of >3 cm thereafter; n = 7). Results: In 3 of 7 nonresponders, the Ki-67 index markedly increased in untreated tumors, whereas Ki-67 was stable in all responders. Microvascular density strongly increased in a single nonresponder only. HGF and angiopoietin-2 increased by >30% in 3 of 7 and 4 of 7 nonresponders, respectively, whereas they were stable or decreased in responders. Overall, ≥2 biomarkers were elevated in 6 of 7 (85.7%) nonresponders, whereas 4 of 6 responders demonstrated no increased biomarker and 2 patients demonstrated increase in 1 biomarker only (P = .002). Conclusions: RF ablation of HCC can produce protumorigenic factors that induce effects in distant untreated tumors. These may potentially function as biomarkers of clinical outcome.",

author = "Matthias Stechele and Moritz Wildgruber and Aurelia Markezana and Sophia K{\"a}stle and Elif {\"O}cal and Kimm, {Melanie A.} and Marianna Alunni-Fabbroni and Mor Paldor and Liao Haixing and Lukas Salvermoser and Maciej Pech and Maciej Powerski and Eithan Galun and Jens Ricke and Goldberg, {Shraga Nahum}",

note = "Funding Information: M.S. reports a travel grant from Rolf W. Guenther Foundation. M.W. is on the advisory board for iThera Medical Munich and receives lecture fees from Bayer Consumer Health. L.S. received grants from Deutsche Forschungsgesellschaft and Walter-Benjamin Program. S.N.G. reports grant support to institution from the Israel Science Foundation (904-2020), receives consulting fees from Cambridge Interventional and Xact Medical (to institution), and reports a travel grant from Rolf W. Guenther Foundation. None of the other authors have identified a conflict of interest. Publisher Copyright: {\textcopyright} 2022 SIR",

year = "2023",

doi = "10.1016/j.jvir.2022.11.024",

language = "American English",

journal = "Journal of Vascular and Interventional Radiology",

issn = "1051-0443",

publisher = "Elsevier Inc.",

}

Stechele, M, Wildgruber, M, Markezana, A, Kästle, S, Öcal, E, Kimm, MA, Alunni-Fabbroni, M, Paldor, M, Haixing, L, Salvermoser, L, Pech, M, Powerski, M, Galun, E, Ricke, J & Goldberg, SN 2023, 'Prediction of Protumorigenic Effects after Image-Guided Radiofrequency Ablation of Hepatocellular Carcinoma Using Biomarkers', Journal of Vascular and Interventional Radiology. https://doi.org/10.1016/j.jvir.2022.11.024

TY - JOUR

T1 - Prediction of Protumorigenic Effects after Image-Guided Radiofrequency Ablation of Hepatocellular Carcinoma Using Biomarkers

AU - Stechele, Matthias

AU - Wildgruber, Moritz

AU - Markezana, Aurelia

AU - Kästle, Sophia

AU - Öcal, Elif

AU - Kimm, Melanie A.

AU - Alunni-Fabbroni, Marianna

AU - Paldor, Mor

AU - Haixing, Liao

AU - Salvermoser, Lukas

AU - Pech, Maciej

AU - Powerski, Maciej

AU - Galun, Eithan

AU - Ricke, Jens

AU - Goldberg, Shraga Nahum

N1 - Funding Information: M.S. reports a travel grant from Rolf W. Guenther Foundation. M.W. is on the advisory board for iThera Medical Munich and receives lecture fees from Bayer Consumer Health. L.S. received grants from Deutsche Forschungsgesellschaft and Walter-Benjamin Program. S.N.G. reports grant support to institution from the Israel Science Foundation (904-2020), receives consulting fees from Cambridge Interventional and Xact Medical (to institution), and reports a travel grant from Rolf W. Guenther Foundation. None of the other authors have identified a conflict of interest. Publisher Copyright: © 2022 SIR

PY - 2023

Y1 - 2023

N2 - Purpose: To perform radiofrequency (RF) ablation of hepatocellular carcinoma (HCC) and to assess serological and histopathological markers of tumorigenesis in distant untreated tumors to determine whether these were associated with unfavorable outcomes such as early relapse and increased biological aggressiveness. Materials and Methods: The study cohort comprised 13 patients from a prospective single-arm study. All patients underwent 2 ablation sessions of multifocal HCC nodules 14 days apart. Core biopsy samples of untreated tumors were acquired at baseline and at the time of the second ablation session. Samples were stained immunohistochemically with Ki-67 (proliferation) and CD34 (microvasculature). Blood plasma was obtained at baseline and 2 days after the initial ablation session and analyzed for hepatocyte growth factor (HGF), vascular endothelial growth factor C, and angiopoietin-2 using an enzyme-linked immunosorbent assay. The clinical follow-up period ranged from 7 to 25 months. Patients were stratified as responders (complete remission or limited and delayed recurrence at >6 months; n = 6) or nonresponders (any recurrence within 6 months or >3 new tumors or any new tumor of >3 cm thereafter; n = 7). Results: In 3 of 7 nonresponders, the Ki-67 index markedly increased in untreated tumors, whereas Ki-67 was stable in all responders. Microvascular density strongly increased in a single nonresponder only. HGF and angiopoietin-2 increased by >30% in 3 of 7 and 4 of 7 nonresponders, respectively, whereas they were stable or decreased in responders. Overall, ≥2 biomarkers were elevated in 6 of 7 (85.7%) nonresponders, whereas 4 of 6 responders demonstrated no increased biomarker and 2 patients demonstrated increase in 1 biomarker only (P = .002). Conclusions: RF ablation of HCC can produce protumorigenic factors that induce effects in distant untreated tumors. These may potentially function as biomarkers of clinical outcome.

AB - Purpose: To perform radiofrequency (RF) ablation of hepatocellular carcinoma (HCC) and to assess serological and histopathological markers of tumorigenesis in distant untreated tumors to determine whether these were associated with unfavorable outcomes such as early relapse and increased biological aggressiveness. Materials and Methods: The study cohort comprised 13 patients from a prospective single-arm study. All patients underwent 2 ablation sessions of multifocal HCC nodules 14 days apart. Core biopsy samples of untreated tumors were acquired at baseline and at the time of the second ablation session. Samples were stained immunohistochemically with Ki-67 (proliferation) and CD34 (microvasculature). Blood plasma was obtained at baseline and 2 days after the initial ablation session and analyzed for hepatocyte growth factor (HGF), vascular endothelial growth factor C, and angiopoietin-2 using an enzyme-linked immunosorbent assay. The clinical follow-up period ranged from 7 to 25 months. Patients were stratified as responders (complete remission or limited and delayed recurrence at >6 months; n = 6) or nonresponders (any recurrence within 6 months or >3 new tumors or any new tumor of >3 cm thereafter; n = 7). Results: In 3 of 7 nonresponders, the Ki-67 index markedly increased in untreated tumors, whereas Ki-67 was stable in all responders. Microvascular density strongly increased in a single nonresponder only. HGF and angiopoietin-2 increased by >30% in 3 of 7 and 4 of 7 nonresponders, respectively, whereas they were stable or decreased in responders. Overall, ≥2 biomarkers were elevated in 6 of 7 (85.7%) nonresponders, whereas 4 of 6 responders demonstrated no increased biomarker and 2 patients demonstrated increase in 1 biomarker only (P = .002). Conclusions: RF ablation of HCC can produce protumorigenic factors that induce effects in distant untreated tumors. These may potentially function as biomarkers of clinical outcome.

UR - http://www.scopus.com/inward/record.url?scp=85163361533&partnerID=8YFLogxK

U2 - 10.1016/j.jvir.2022.11.024

DO - 10.1016/j.jvir.2022.11.024

M3 - Article

C2 - 36442741

AN - SCOPUS:85163361533

SN - 1051-0443

JO - Journal of Vascular and Interventional Radiology

JF - Journal of Vascular and Interventional Radiology

ER -

Prediction of Protumorigenic Effects after Image-Guided Radiofrequency Ablation of Hepatocellular Carcinoma Using Biomarkers

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