Skip to main content
Erschienen in: Targeted Oncology 6/2020

12.10.2020 | Original Research Article

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

verfasst von: 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

Erschienen in: Targeted Oncology | Ausgabe 6/2020

Einloggen, um Zugang zu erhalten

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.
Literatur
2.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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
49.
50.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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
Metadaten
Titel
Prognostic Role of Blood Eosinophil Count in Patients with Sorafenib-Treated Hepatocellular Carcinoma
verfasst von
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
Publikationsdatum
12.10.2020
Verlag
Springer International Publishing
Erschienen in
Targeted Oncology / Ausgabe 6/2020
Print ISSN: 1776-2596
Elektronische ISSN: 1776-260X
DOI
https://doi.org/10.1007/s11523-020-00757-3

Weitere Artikel der Ausgabe 6/2020

Targeted Oncology 6/2020 Zur Ausgabe

Acknowledgement to Referees

Acknowledgement to Referees

Labor, CT-Anthropometrie zeigen Risiko für Pankreaskrebs

13.05.2024 Pankreaskarzinom Nachrichten

Gerade bei aggressiven Malignomen wie dem duktalen Adenokarzinom des Pankreas könnte Früherkennung die Therapiechancen verbessern. Noch jedoch klafft hier eine Lücke. Ein Studienteam hat einen Weg gesucht, sie zu schließen.

Viel pflanzliche Nahrung, seltener Prostata-Ca.-Progression

12.05.2024 Prostatakarzinom Nachrichten

Ein hoher Anteil pflanzlicher Nahrung trägt möglicherweise dazu bei, das Progressionsrisiko von Männern mit Prostatakarzinomen zu senken. In einer US-Studie war das Risiko bei ausgeprägter pflanzlicher Ernährung in etwa halbiert.

Alter verschlechtert Prognose bei Endometriumkarzinom

11.05.2024 Endometriumkarzinom Nachrichten

Ein höheres Alter bei der Diagnose eines Endometriumkarzinoms ist mit aggressiveren Tumorcharakteristika assoziiert, scheint aber auch unabhängig von bekannten Risikofaktoren die Prognose der Erkrankung zu verschlimmern.

Darf man die Behandlung eines Neonazis ablehnen?

08.05.2024 Gesellschaft Nachrichten

In einer Leseranfrage in der Zeitschrift Journal of the American Academy of Dermatology möchte ein anonymer Dermatologe bzw. eine anonyme Dermatologin wissen, ob er oder sie einen Patienten behandeln muss, der eine rassistische Tätowierung trägt.

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.