Skip to main content
Top
Published in: Targeted Oncology 6/2020

01-12-2020 | Portal Vein Thrombosis | Original Research Article

Prognostic Role of Blood Eosinophil Count in Patients with Sorafenib-Treated Hepatocellular Carcinoma

Authors: Giulia Orsi, Francesco Tovoli, Vincenzo Dadduzio, Caterina Vivaldi, Oronzo Brunetti, Luca Ielasi, Fabio Conti, Giulia Rovesti, Laura Gramantieri, Mario Domenico Rizzato, Irene Pecora, Antonella Argentiero, Federica Teglia, Sara Lonardi, Francesca Salani, Alessandro Granito, Vittorina Zagonel, Giorgia Marisi, Giuseppe Cabibbo, Francesco Giuseppe Foschi, Francesca Benevento, Alessandro Cucchetti, Fabio Piscaglia, Stefano Cascinu, Mario Scartozzi, Andrea Casadei-Gardini

Published in: Targeted Oncology | Issue 6/2020

Login to get access

Abstract

Background

Inflammation is a long-established hallmark of liver fibrosis and carcinogenesis. Eosinophils are emerging as crucial components of the inflammatory process influencing cancer development. The role of blood eosinophils in patients with hepatocellular carcinoma receiving systemic treatment is an unexplored field.

Objective

The objective of this study was to analyse the prognostic role of the baseline eosinophil count in patients with sorafenib-treated hepatocellular carcinoma.

Patients and Methods

A training cohort of 92 patients with advanced- or intermediate-stage sorafenib-treated hepatocellular carcinoma and two validation cohorts of 65 and 180 patients were analysed. Overall survival and progression-free survival in relation to baseline eosinophil counts were estimated by the Kaplan–Meier method. Univariate and multivariate analyses were performed.

Results

A negative prognostic impact of low baseline eosinophil counts (< 50*109/L) was demonstrated in all cohorts (training cohort: hazard ratio = 50.1, 95% confidence interval 11.6–216.5, p < 0.0001 for low vs high eosinophil counts; first validation cohort: hazard ratio = 4.55, 95% confidence interval 1.24–16.65, p = 0.022; second validation cohort: hazard ratio = 3.21, 95% confidence interval 1.83–5.64, p < 0.0001). Moreover, low eosinophil counts had a negative prognostic role in patients progressing on or intolerant to sorafenib who received second-line regorafenib, but not capecitabine or best supportive care.

Conclusions

Our analysis identified baseline blood eosinophil counts as a new prognostic factor in patients with sorafenib-treated hepatocellular carcinoma. Concerning second-line therapies, eosinophil counts were associated with survival outcomes only in regorafenib-treated patients, suggesting a possible predictive role in this setting.
Literature
2.
go back to reference Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424.PubMedCrossRef Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424.PubMedCrossRef
3.
go back to reference Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc J-F, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008;359(4):378–90.PubMedCrossRef Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc J-F, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008;359(4):378–90.PubMedCrossRef
4.
go back to reference Cheng AL, Kang Y-K, Chen Z, Tsao C-J, Qin S, Kim JS, et al. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2009;10(1):25–34.PubMedCrossRef Cheng AL, Kang Y-K, Chen Z, Tsao C-J, Qin S, Kim JS, et al. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2009;10(1):25–34.PubMedCrossRef
5.
go back to reference European Association for the Study of the Liver. EASL clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol. 2018;69:182–236.CrossRef European Association for the Study of the Liver. EASL clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol. 2018;69:182–236.CrossRef
6.
go back to reference Heimbach JK, Kulik LM, Finn RS, Sirlin CB, Abecassis MM, Roberts LR, et al. AASLD guidelines for the treatment of hepatocellular carcinoma. Hepatology. 2018;67:358–80.PubMedCrossRef Heimbach JK, Kulik LM, Finn RS, Sirlin CB, Abecassis MM, Roberts LR, et al. AASLD guidelines for the treatment of hepatocellular carcinoma. Hepatology. 2018;67:358–80.PubMedCrossRef
7.
go back to reference Kudo M, Finn RS, Qin S, Han K-H, Ikeda K, Piscaglia F, et al. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial. Lancet. 2018;391(10126):1163–73.PubMedCrossRef Kudo M, Finn RS, Qin S, Han K-H, Ikeda K, Piscaglia F, et al. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial. Lancet. 2018;391(10126):1163–73.PubMedCrossRef
8.
go back to reference Bruix J, Qin S, Merle P, Granito A, Huang Y-H, Bodoky G, et al. Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo controlled, phase 3 trial. Lancet. 2017;389(10064):56–66.PubMedCrossRef Bruix J, Qin S, Merle P, Granito A, Huang Y-H, Bodoky G, et al. Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo controlled, phase 3 trial. Lancet. 2017;389(10064):56–66.PubMedCrossRef
9.
go back to reference Zhu AX, Kang Y-K, Yen C-J, Finn RS, Galle PR, Llovet JM, et al. Ramucirumab after sorafenib in patients with advanced hepatocellular carcinoma and increased α-fetoprotein concentrations (REACH-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2019;20(2):282–96.PubMedCrossRef Zhu AX, Kang Y-K, Yen C-J, Finn RS, Galle PR, Llovet JM, et al. Ramucirumab after sorafenib in patients with advanced hepatocellular carcinoma and increased α-fetoprotein concentrations (REACH-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2019;20(2):282–96.PubMedCrossRef
10.
go back to reference Abou-Alfa GK, Meyer T, Cheng A-L, El-Khoueiry AB, Rimassa L, Ryooet B-Y, et al. Cabozantinib in patients with advanced and progressing hepatocellular carcinoma. N Engl J Med. 2018;379(1):54–63.PubMedPubMedCentralCrossRef Abou-Alfa GK, Meyer T, Cheng A-L, El-Khoueiry AB, Rimassa L, Ryooet B-Y, et al. Cabozantinib in patients with advanced and progressing hepatocellular carcinoma. N Engl J Med. 2018;379(1):54–63.PubMedPubMedCentralCrossRef
11.
go back to reference Tovoli F, Casadei-Gardini A, Benevento F, Piscaglia F. Immunotherapy for hepatocellular carcinoma: a review of potential new drugs based on ongoing clinical studies as of 2019. Dig Liver Dis. 2019;51(8):1067–73.PubMedCrossRef Tovoli F, Casadei-Gardini A, Benevento F, Piscaglia F. Immunotherapy for hepatocellular carcinoma: a review of potential new drugs based on ongoing clinical studies as of 2019. Dig Liver Dis. 2019;51(8):1067–73.PubMedCrossRef
12.
go back to reference El-Khoueiry AB, Sangro B, Yau T, Crocenzi TS, Kudo M, Hsuet C, et al. Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase 1/2 dose escalation and expansion trial. Lancet. 2017;389(10088):2492–502.PubMedPubMedCentralCrossRef El-Khoueiry AB, Sangro B, Yau T, Crocenzi TS, Kudo M, Hsuet C, et al. Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase 1/2 dose escalation and expansion trial. Lancet. 2017;389(10088):2492–502.PubMedPubMedCentralCrossRef
13.
go back to reference Zhu AX, Finn RS, Edeline J, Cattan S, Ogasawara S, Palmeret D, et al. Pembrolizumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib (KEYNOTE-224): a non-randomised, open-label phase 2 trial. Lancet Oncol. 2018;19(7):940–52.PubMedCrossRef Zhu AX, Finn RS, Edeline J, Cattan S, Ogasawara S, Palmeret D, et al. Pembrolizumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib (KEYNOTE-224): a non-randomised, open-label phase 2 trial. Lancet Oncol. 2018;19(7):940–52.PubMedCrossRef
14.
go back to reference Finn RS, Ryoo B-Y, Merle P, Kudo M, Bouattour M, Lim H-Y, et al. Results of KEYNOTE-240: phase 3 study of pembrolizumab (Pembro) vs. best supportive care (BSC) for second line therapy in advanced hepatocellular carcinoma (HCC). J Clin Oncol. 2019;37(15_Suppl.):4004. Finn RS, Ryoo B-Y, Merle P, Kudo M, Bouattour M, Lim H-Y, et al. Results of KEYNOTE-240: phase 3 study of pembrolizumab (Pembro) vs. best supportive care (BSC) for second line therapy in advanced hepatocellular carcinoma (HCC). J Clin Oncol. 2019;37(15_Suppl.):4004.
15.
go back to reference Yau T, Park JW, Finn RS, Cheng A-L, Mathurin P, Edeline J, et al. CheckMate 459: a randomized, multi-center phase III study of nivolumab (NIVO) vs sorafenib (SOR) as first-line (1L) treatment in patients (pts) with advanced hepatocellular carcinoma (aHCC). Ann Oncol. 2019;30(5_Suppl.):v874–5. Yau T, Park JW, Finn RS, Cheng A-L, Mathurin P, Edeline J, et al. CheckMate 459: a randomized, multi-center phase III study of nivolumab (NIVO) vs sorafenib (SOR) as first-line (1L) treatment in patients (pts) with advanced hepatocellular carcinoma (aHCC). Ann Oncol. 2019;30(5_Suppl.):v874–5.
16.
go back to reference Finn RS, Qin S, Ikeda M, Galle PR, Ducreux M, Kim T-Y, et al. Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma. N Engl J Med. 2020;382(20):1894–905.PubMedCrossRef Finn RS, Qin S, Ikeda M, Galle PR, Ducreux M, Kim T-Y, et al. Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma. N Engl J Med. 2020;382(20):1894–905.PubMedCrossRef
18.
go back to reference Sanghera C, Teh JJ, Pinato DJ. The systemic inflammatory response as a source of biomarkers and therapeutic targets in hepatocellular carcinoma. Liver Int. 2019;39(11):2008–233.PubMedCrossRef Sanghera C, Teh JJ, Pinato DJ. The systemic inflammatory response as a source of biomarkers and therapeutic targets in hepatocellular carcinoma. Liver Int. 2019;39(11):2008–233.PubMedCrossRef
19.
go back to reference Ogunwobi OO, Harricharran T, Huaman J, Galuza A, Odumuwagun O, Tanet Y, et al. Mechanisms of hepatocellular carcinoma progression. World J Gastroenterol. 2019;25(19):2279–93.PubMedPubMedCentralCrossRef Ogunwobi OO, Harricharran T, Huaman J, Galuza A, Odumuwagun O, Tanet Y, et al. Mechanisms of hepatocellular carcinoma progression. World J Gastroenterol. 2019;25(19):2279–93.PubMedPubMedCentralCrossRef
20.
go back to reference Hernandez-Gea V, Toffanin S, Friedman SL, Llovet JM. Role of the microenvironment in the pathogenesis and treatment of hepatocellular carcinoma. Gastroenterology. 2013;144(3):512–27.PubMedCrossRef Hernandez-Gea V, Toffanin S, Friedman SL, Llovet JM. Role of the microenvironment in the pathogenesis and treatment of hepatocellular carcinoma. Gastroenterology. 2013;144(3):512–27.PubMedCrossRef
21.
go back to reference Budhu A, Wang XW. The role of cytokines in hepatocellular carcinoma. J Leukocyte Biol. 2006;80(6):1197–213.PubMedCrossRef Budhu A, Wang XW. The role of cytokines in hepatocellular carcinoma. J Leukocyte Biol. 2006;80(6):1197–213.PubMedCrossRef
22.
go back to reference Budhu A, Forgues M, Ye Q-H, Jia H-L, He P, Zanetti KA, et al. Prediction of venous metastases, recurrence, and prognosis in hepatocellular carcinoma based on a unique immune response signature of the liver microenvironment. Cancer Cell. 2006;10(2):99–111.PubMedCrossRef Budhu A, Forgues M, Ye Q-H, Jia H-L, He P, Zanetti KA, et al. Prediction of venous metastases, recurrence, and prognosis in hepatocellular carcinoma based on a unique immune response signature of the liver microenvironment. Cancer Cell. 2006;10(2):99–111.PubMedCrossRef
23.
go back to reference Zhou H, Huang H, Shi J, Zhao Y, Dong Q, Jia H, et al. Prognostic value of interleukin 2 and interleukin 15 in peritumoral hepatic tissues for patients with hepatitis B-related hepatocellular carcinoma after curative resection. Gut. 2010;59(12):1699–708.PubMedCrossRef Zhou H, Huang H, Shi J, Zhao Y, Dong Q, Jia H, et al. Prognostic value of interleukin 2 and interleukin 15 in peritumoral hepatic tissues for patients with hepatitis B-related hepatocellular carcinoma after curative resection. Gut. 2010;59(12):1699–708.PubMedCrossRef
24.
go back to reference Bruix J, Cheng AL, Meinhardt G, Nakajima K, De Sanctis Y, Llove L. Prognostic factors and predictors of Sorafenib benefit in patients with hepatocellular carcinoma: analysis of two phase III studies. J Hepatol. 2017;67(5):999–1008.PubMedCrossRef Bruix J, Cheng AL, Meinhardt G, Nakajima K, De Sanctis Y, Llove L. Prognostic factors and predictors of Sorafenib benefit in patients with hepatocellular carcinoma: analysis of two phase III studies. J Hepatol. 2017;67(5):999–1008.PubMedCrossRef
25.
go back to reference Da Fonseca LG, Barroso-Sousa R, Bento Ada S, Blanco BP, Valente GL, Pfiffer TE, et al. Pre-treatment neutrophil-to-lymphocyte ratio affects survival in patients with advanced hepatocellular carcinoma treated with sorafenib. Med Oncol. 2014;31:264.PubMedCrossRef Da Fonseca LG, Barroso-Sousa R, Bento Ada S, Blanco BP, Valente GL, Pfiffer TE, et al. Pre-treatment neutrophil-to-lymphocyte ratio affects survival in patients with advanced hepatocellular carcinoma treated with sorafenib. Med Oncol. 2014;31:264.PubMedCrossRef
26.
go back to reference Howell J, Pinato DJ, Ramaswami R, Arizumi T, Ferrari C, Gibbin A, et al. Integration of the cancer-related inflammatory response as a stratifying biomarker of survival in hepatocellular carcinoma treated with sorafenib. Oncotarget. 2017;8:36161–700.PubMedPubMedCentralCrossRef Howell J, Pinato DJ, Ramaswami R, Arizumi T, Ferrari C, Gibbin A, et al. Integration of the cancer-related inflammatory response as a stratifying biomarker of survival in hepatocellular carcinoma treated with sorafenib. Oncotarget. 2017;8:36161–700.PubMedPubMedCentralCrossRef
27.
go back to reference Lué A, Serrano MT, Bustamante FJ, Iñarrairaegui M, Arenas JI, Testillano M, et al. Neutrophil-to-lymphocyte ratio predicts survival in European patients with hepatocellular carcinoma administered sorafenib. Oncotarget. 2017;8:103077–86.PubMedPubMedCentralCrossRef Lué A, Serrano MT, Bustamante FJ, Iñarrairaegui M, Arenas JI, Testillano M, et al. Neutrophil-to-lymphocyte ratio predicts survival in European patients with hepatocellular carcinoma administered sorafenib. Oncotarget. 2017;8:103077–86.PubMedPubMedCentralCrossRef
28.
go back to reference Casadei Gardini A, Scarpi E, Faloppi L, Scartozzi M, Silvestris N, Santini D, et al. Immune inflammation indicators and implication for immune modulation strategies in advanced hepatocellular carcinoma patients receiving sorafenib. Oncotarget. 2016;7(41):67142–9.PubMedCrossRef Casadei Gardini A, Scarpi E, Faloppi L, Scartozzi M, Silvestris N, Santini D, et al. Immune inflammation indicators and implication for immune modulation strategies in advanced hepatocellular carcinoma patients receiving sorafenib. Oncotarget. 2016;7(41):67142–9.PubMedCrossRef
29.
go back to reference Varricchi G, Galdiero MR, Loffredo S, Lucarini V, Marone G, Mattei F, et al. Eosinophils: the unsung heroes in cancer? Oncoimmunology. 2017;7(2):e1393134.PubMedPubMedCentralCrossRef Varricchi G, Galdiero MR, Loffredo S, Lucarini V, Marone G, Mattei F, et al. Eosinophils: the unsung heroes in cancer? Oncoimmunology. 2017;7(2):e1393134.PubMedPubMedCentralCrossRef
30.
go back to reference Zahoor H, Barata PC, Jia X, Martin A, Allman KD, Wood LS, et al. Patterns, predictors and subsequent outcomes of disease progression in metastatic renal cell carcinoma patients treated with nivolumab. J Immunother Cancer. 2018;6(1):107.PubMedPubMedCentralCrossRef Zahoor H, Barata PC, Jia X, Martin A, Allman KD, Wood LS, et al. Patterns, predictors and subsequent outcomes of disease progression in metastatic renal cell carcinoma patients treated with nivolumab. J Immunother Cancer. 2018;6(1):107.PubMedPubMedCentralCrossRef
31.
go back to reference Rosner S, Kwong E, Shoushtari AN, Friedman CF, Betof AS, Bradye MS, et al. Peripheral blood clinical laboratory variables associated with outcomes following combination nivolumab and ipilimumab immunotherapy in melanoma. Cancer Med. 2018;7(3):690–7.PubMedPubMedCentralCrossRef Rosner S, Kwong E, Shoushtari AN, Friedman CF, Betof AS, Bradye MS, et al. Peripheral blood clinical laboratory variables associated with outcomes following combination nivolumab and ipilimumab immunotherapy in melanoma. Cancer Med. 2018;7(3):690–7.PubMedPubMedCentralCrossRef
32.
go back to reference Wei Y, Zhang X, Wang G, Zhou Y, Luo M, Wang S, et al. The impacts of pretreatment circulating eosinophils and basophils on prognosis of stage I–III colorectal cancer. Asia Pac J Clin Oncol. 2018;14(5):e243–e251251.PubMedCrossRef Wei Y, Zhang X, Wang G, Zhou Y, Luo M, Wang S, et al. The impacts of pretreatment circulating eosinophils and basophils on prognosis of stage I–III colorectal cancer. Asia Pac J Clin Oncol. 2018;14(5):e243–e251251.PubMedCrossRef
33.
go back to reference Tanizaki J, Haratani K, Hayashi H, Chiba Y, Nakamura Y, Yonesaka K, et al. Peripheral blood biomarkers associated with clinical outcome in non-small cell lung cancer patients treated with nivolumab. J Thorac Oncol. 2018;13(1):97–105.PubMedCrossRef Tanizaki J, Haratani K, Hayashi H, Chiba Y, Nakamura Y, Yonesaka K, et al. Peripheral blood biomarkers associated with clinical outcome in non-small cell lung cancer patients treated with nivolumab. J Thorac Oncol. 2018;13(1):97–105.PubMedCrossRef
34.
go back to reference Holub K, Biete A. Impact of systemic inflammation biomarkers on the survival outcomes of cervical cancer patients. Clin Transl Oncol. 2019;21(7):836–44.PubMedCrossRef Holub K, Biete A. Impact of systemic inflammation biomarkers on the survival outcomes of cervical cancer patients. Clin Transl Oncol. 2019;21(7):836–44.PubMedCrossRef
35.
go back to reference Holub K, Conill C. Unveiling the mechanisms of immune evasion in pancreatic cancer: may it be a systemic inflammation responsible for dismal survival? Clin Transl Oncol. 2020;22(1):81–90.PubMedCrossRef Holub K, Conill C. Unveiling the mechanisms of immune evasion in pancreatic cancer: may it be a systemic inflammation responsible for dismal survival? Clin Transl Oncol. 2020;22(1):81–90.PubMedCrossRef
36.
go back to reference Ownby HE, Roi LD, Isenberg RR, Brennan MJ. Peripheral lymphocyte and eosinophil counts as indicators of prognosis in primary breast cancer. Cancer. 1983;52(1):126–30.PubMedCrossRef Ownby HE, Roi LD, Isenberg RR, Brennan MJ. Peripheral lymphocyte and eosinophil counts as indicators of prognosis in primary breast cancer. Cancer. 1983;52(1):126–30.PubMedCrossRef
37.
go back to reference Utsunomiya A, Ishida T, Inagaki A, Ishii T, Yano H, Komatsu H, et al. Clinical significance of a blood eosinophilia in adult T-cell leukemia/lymphoma: a blood eosinophilia is a significant unfavorable prognostic factor. Leuk Res. 2007;31(7):915–20.PubMedCrossRef Utsunomiya A, Ishida T, Inagaki A, Ishii T, Yano H, Komatsu H, et al. Clinical significance of a blood eosinophilia in adult T-cell leukemia/lymphoma: a blood eosinophilia is a significant unfavorable prognostic factor. Leuk Res. 2007;31(7):915–20.PubMedCrossRef
38.
go back to reference Hude I, Sasse S, Bröckelmann PJ, von Tresckow B, Momotow J, Engert A, et al. Leucocyte and eosinophil counts predict progression-free survival in relapsed or refractory classical Hodgkin lymphoma patients treated with PD1 inhibition. Br J Haematol. 2018;181(6):837–40.PubMedCrossRef Hude I, Sasse S, Bröckelmann PJ, von Tresckow B, Momotow J, Engert A, et al. Leucocyte and eosinophil counts predict progression-free survival in relapsed or refractory classical Hodgkin lymphoma patients treated with PD1 inhibition. Br J Haematol. 2018;181(6):837–40.PubMedCrossRef
39.
go back to reference Steel JL, Kim KH, Dew MA, Unruh ML, Antoni MH, Olek MC, et al. Cancer-related symptom clusters, eosinophils, and survival in hepatobiliary cancer: an exploratory study. J Pain Symptom Manag. 2010;39(5):859–71.CrossRef Steel JL, Kim KH, Dew MA, Unruh ML, Antoni MH, Olek MC, et al. Cancer-related symptom clusters, eosinophils, and survival in hepatobiliary cancer: an exploratory study. J Pain Symptom Manag. 2010;39(5):859–71.CrossRef
40.
go back to reference Casadei Gardini A, Marisi G, Dadduzio V, Gramantieri L, Faloppi L, Ulivi P, et al. Association of NOS3 and ANGPT2 gene polymorphisms with survival in patients with hepatocellular carcinoma receiving sorafenib: results of the multicenter prospective INNOVATE study. Clin Cancer Res. 2020;26(17):4485–93.PubMedCrossRef Casadei Gardini A, Marisi G, Dadduzio V, Gramantieri L, Faloppi L, Ulivi P, et al. Association of NOS3 and ANGPT2 gene polymorphisms with survival in patients with hepatocellular carcinoma receiving sorafenib: results of the multicenter prospective INNOVATE study. Clin Cancer Res. 2020;26(17):4485–93.PubMedCrossRef
41.
go back to reference Casadei Gardini A, Foca F, Scartozzi M, Silvestris N, Tamburini E, Faloppi L, et al. Metronomic capecitabine versus best supportive care as second-line treatment in hepatocellular carcinoma: a retrospective study. Sci Rep. 2017;7:42499.PubMedPubMedCentralCrossRef Casadei Gardini A, Foca F, Scartozzi M, Silvestris N, Tamburini E, Faloppi L, et al. Metronomic capecitabine versus best supportive care as second-line treatment in hepatocellular carcinoma: a retrospective study. Sci Rep. 2017;7:42499.PubMedPubMedCentralCrossRef
42.
go back to reference Pelizzaro F, Sammarco A, Dadduzio V, Pastorelli D, Giovanis P, Soldà C, et al. Capecitabine in advanced hepatocellular carcinoma: a multicenter experience. Dig Liver Dis. 2019;51(12):1713–9.PubMedCrossRef Pelizzaro F, Sammarco A, Dadduzio V, Pastorelli D, Giovanis P, Soldà C, et al. Capecitabine in advanced hepatocellular carcinoma: a multicenter experience. Dig Liver Dis. 2019;51(12):1713–9.PubMedCrossRef
43.
go back to reference McDonald JH. Fisher’s exact test of independence. In: Handbook of biological statistics. 3rd ed. Baltimore, Maryland: Sparky House Publishing; 2014. McDonald JH. Fisher’s exact test of independence. In: Handbook of biological statistics. 3rd ed. Baltimore, Maryland: Sparky House Publishing; 2014.
44.
go back to reference Gunduz S, Mutlu H, Uysal M, Coskun HS, Bozcuk H, et al. Prognostic value of hematologic parameters in patients with metastatic renal cell carcinoma using tyrosine kinase inhibitors. Asian Pac J Cancer Prev. 2014;15(8):3801–4.PubMedCrossRef Gunduz S, Mutlu H, Uysal M, Coskun HS, Bozcuk H, et al. Prognostic value of hematologic parameters in patients with metastatic renal cell carcinoma using tyrosine kinase inhibitors. Asian Pac J Cancer Prev. 2014;15(8):3801–4.PubMedCrossRef
45.
go back to reference Martens A, Wistuba-Hamprecht K, Geukes Foppen M, Yuan J, Postow MA, Wong P, et al. Baseline peripheral blood biomarkers associated with clinical outcome of advanced melanoma patients treated with ipilimumab. Clin Cancer Res. 2016;22(12):2908–18.PubMedPubMedCentralCrossRef Martens A, Wistuba-Hamprecht K, Geukes Foppen M, Yuan J, Postow MA, Wong P, et al. Baseline peripheral blood biomarkers associated with clinical outcome of advanced melanoma patients treated with ipilimumab. Clin Cancer Res. 2016;22(12):2908–18.PubMedPubMedCentralCrossRef
46.
go back to reference Weide B, Martens A, Hassel JC, Berking C, Postow MA, Bisschop K, et al. Baseline biomarkers for outcome of melanoma patients treated with pembrolizumab. Clin Cancer Res. 2016;22(22):5487–96.PubMedPubMedCentralCrossRef Weide B, Martens A, Hassel JC, Berking C, Postow MA, Bisschop K, et al. Baseline biomarkers for outcome of melanoma patients treated with pembrolizumab. Clin Cancer Res. 2016;22(22):5487–96.PubMedPubMedCentralCrossRef
47.
go back to reference Wang HK, Wan FN, Gu WJ, Zhu Y, Dai B, Shi G-H, et al. Eosinophil percentage elevation as a prognostic factor for overall survival in patients with metastatic renal cell carcinoma treated with tyrosine kinase inhibitor. Oncotarget. 2016;7(42):68943–53.PubMedPubMedCentralCrossRef Wang HK, Wan FN, Gu WJ, Zhu Y, Dai B, Shi G-H, et al. Eosinophil percentage elevation as a prognostic factor for overall survival in patients with metastatic renal cell carcinoma treated with tyrosine kinase inhibitor. Oncotarget. 2016;7(42):68943–53.PubMedPubMedCentralCrossRef
48.
go back to reference Gebhardt C, Sevko A, Jiang H, Lichtenberger R, Reith M, Tarnanidis K, et al. Myeloid cells and related chronic inflammatory factors as novel predictive markers in melanoma treatment with ipilimumab. Clin Cancer Res. 2015;21(24):5453–9.PubMedCrossRef Gebhardt C, Sevko A, Jiang H, Lichtenberger R, Reith M, Tarnanidis K, et al. Myeloid cells and related chronic inflammatory factors as novel predictive markers in melanoma treatment with ipilimumab. Clin Cancer Res. 2015;21(24):5453–9.PubMedCrossRef
50.
go back to reference Ramirez GA, Yacoub MR, Ripa M, Mannina D, Cariddi A, Saporiti N, et al. Eosinophils from physiology to disease: a comprehensive review. Biomed Res Int. 2018;2018:9095275.PubMedPubMedCentralCrossRef Ramirez GA, Yacoub MR, Ripa M, Mannina D, Cariddi A, Saporiti N, et al. Eosinophils from physiology to disease: a comprehensive review. Biomed Res Int. 2018;2018:9095275.PubMedPubMedCentralCrossRef
51.
go back to reference Carretero R, Sektioglu IM, Garbi N, Salgado OC, Beckhove P, Hämmerling GJ, et al. Eosinophils orchestrate cancer rejection by normalizing tumor vessels and enhancing infiltration of CD8(+) T cells. Nat Immunol. 2015;16(6):609–17.PubMedCrossRef Carretero R, Sektioglu IM, Garbi N, Salgado OC, Beckhove P, Hämmerling GJ, et al. Eosinophils orchestrate cancer rejection by normalizing tumor vessels and enhancing infiltration of CD8(+) T cells. Nat Immunol. 2015;16(6):609–17.PubMedCrossRef
52.
go back to reference Shomura M, Kagawa T, Shiraishi K, Hirose S, Arase Y, Koizumi J, et al. Skin toxicity predicts efficacy to sorafenib in patients with advanced hepatocellular carcinoma. World J Hepatol. 2014;6(9):670–6.PubMedPubMedCentralCrossRef Shomura M, Kagawa T, Shiraishi K, Hirose S, Arase Y, Koizumi J, et al. Skin toxicity predicts efficacy to sorafenib in patients with advanced hepatocellular carcinoma. World J Hepatol. 2014;6(9):670–6.PubMedPubMedCentralCrossRef
53.
go back to reference Wang P, Tan G, Zhu M, Li W, Zhai B, Sun X, et al. Hand-foot skin reaction is a beneficial indicator of sorafenib therapy for patients with hepatocellular carcinoma: a systemic review and meta-analysis. Expert Rev Gastroenterol Hepatol. 2018;12(1):1–8.PubMedCrossRef Wang P, Tan G, Zhu M, Li W, Zhai B, Sun X, et al. Hand-foot skin reaction is a beneficial indicator of sorafenib therapy for patients with hepatocellular carcinoma: a systemic review and meta-analysis. Expert Rev Gastroenterol Hepatol. 2018;12(1):1–8.PubMedCrossRef
Metadata
Title
Prognostic Role of Blood Eosinophil Count in Patients with Sorafenib-Treated Hepatocellular Carcinoma
Authors
Giulia Orsi
Francesco Tovoli
Vincenzo Dadduzio
Caterina Vivaldi
Oronzo Brunetti
Luca Ielasi
Fabio Conti
Giulia Rovesti
Laura Gramantieri
Mario Domenico Rizzato
Irene Pecora
Antonella Argentiero
Federica Teglia
Sara Lonardi
Francesca Salani
Alessandro Granito
Vittorina Zagonel
Giorgia Marisi
Giuseppe Cabibbo
Francesco Giuseppe Foschi
Francesca Benevento
Alessandro Cucchetti
Fabio Piscaglia
Stefano Cascinu
Mario Scartozzi
Andrea Casadei-Gardini
Publication date
01-12-2020
Publisher
Springer International Publishing
Published in
Targeted Oncology / Issue 6/2020
Print ISSN: 1776-2596
Electronic ISSN: 1776-260X
DOI
https://doi.org/10.1007/s11523-020-00757-3

Other articles of this Issue 6/2020

Targeted Oncology 6/2020 Go to the issue

Adis Biosimilar Brief

SB8: A Bevacizumab Biosimilar

Acknowledgement to Referees

Acknowledgement to Referees

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine