Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratios as Prognostic Biomarkers in Unresectable Hepatocellular Carcinoma Treated with Atezolizumab plus Bevacizumab

Yue Linda Wu; Claudia Angela Maria Fulgenzi; Antonio D’Alessio; Jaekyung Cheon; Naoshi Nishida; Anwaar Saeed; Brooke Wietharn; Antonella Cammarota; Tiziana Pressiani; Nicola Personeni; Matthias Pinter; Bernhard Scheiner; Lorenz Balcar; Yi Hsiang Huang; Samuel Phen; Abdul Rafeh Naqash; Caterina Vivaldi; Francesca Salani; Gianluca Masi; Dominik Bettinger; Arndt Vogel; Martin Schönlein; Johann von Felden; Kornelius Schulze; Henning Wege; Peter R. Galle; Masatoshi Kudo; Lorenza Rimassa; Amit G. Singal; Rohini Sharma; Alessio Cortellini; Vincent E. Gaillard; Hong Jae Chon; David J. Pinato; Celina Ang

doi:10.3390/cancers14235834

Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratios as Prognostic Biomarkers in Unresectable Hepatocellular Carcinoma Treated with Atezolizumab plus Bevacizumab

Yue Linda Wu, Claudia Angela Maria Fulgenzi, Antonio D’Alessio, Jaekyung Cheon, Naoshi Nishida, Anwaar Saeed, Brooke Wietharn, Antonella Cammarota, Tiziana Pressiani, Nicola Personeni, Matthias Pinter, Bernhard Scheiner, Lorenz Balcar, Yi Hsiang Huang, Samuel Phen, Abdul Rafeh Naqash, Caterina Vivaldi, Francesca Salani, Gianluca Masi, Dominik BettingerArndt Vogel, Martin Schönlein, Johann von Felden, Kornelius Schulze, Henning Wege, Peter R. Galle, Masatoshi Kudo, Lorenza Rimassa, Amit G. Singal, Rohini Sharma, Alessio Cortellini, Vincent E. Gaillard, Hong Jae Chon, David J. Pinato, Celina Ang

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

24 Scopus citations

Abstract

Systemic inflammation is a key risk factor for hepatocellular carcinoma (HCC) progression and poor outcomes. Inflammatory markers such as the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) may have prognostic value in HCC treated with standard of care atezolizumab plus bevacizumab (Atezo-Bev). We conducted a multicenter, international retrospective cohort study of patients with unresectable HCC treated with Atezo-Bev to assess the association of NLR and PLR with overall survival (OS), progression-free survival (PFS), and objective response rates. Patients with NLR ≥ 5 had a significantly shorter OS (9.38 vs. 16.79 months, p < 0.001) and PFS (4.90 vs. 7.58 months, p = 0.03) compared to patients with NLR < 5. NLR ≥ 5 was an independent prognosticator of worse OS (HR 2.01, 95% CI 1.22–3.56, p = 0.007) but not PFS. PLR ≥ 300 was also significantly associated with decreased OS (9.38 vs. 15.72 months, p = 0.007) and PFS (3.45 vs. 7.11 months, p = 0.04) compared to PLR < 300, but it was not an independent prognosticator of OS or PFS. NLR and PLR were not associated with objective response or disease control rates. NLR ≥ 5 independently prognosticated worse survival outcomes and is worthy of further study and validation.

Original language	English (US)
Article number	5834
Journal	Cancers
Volume	14
Issue number	23
DOIs	https://doi.org/10.3390/cancers14235834
State	Published - Dec 2022

Keywords

NLR
PLR
atezolizumab plus bevacizumab
hepatocellular carcinoma
immunotherapy
inflammatory markers

ASJC Scopus subject areas

Oncology
Cancer Research

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10.3390/cancers14235834

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Wu, Y. L., Fulgenzi, C. A. M., D’Alessio, A., Cheon, J., Nishida, N., Saeed, A., Wietharn, B., Cammarota, A., Pressiani, T., Personeni, N., Pinter, M., Scheiner, B., Balcar, L., Huang, Y. H., Phen, S., Naqash, A. R., Vivaldi, C., Salani, F., Masi, G., ... Ang, C. (2022). Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratios as Prognostic Biomarkers in Unresectable Hepatocellular Carcinoma Treated with Atezolizumab plus Bevacizumab. Cancers, 14(23), Article 5834. https://doi.org/10.3390/cancers14235834

Wu, YL, Fulgenzi, CAM, D’Alessio, A, Cheon, J, Nishida, N, Saeed, A, Wietharn, B, Cammarota, A, Pressiani, T, Personeni, N, Pinter, M, Scheiner, B, Balcar, L, Huang, YH, Phen, S, Naqash, AR, Vivaldi, C, Salani, F, Masi, G, Bettinger, D, Vogel, A, Schönlein, M, von Felden, J, Schulze, K, Wege, H, Galle, PR, Kudo, M, Rimassa, L, Singal, AG, Sharma, R, Cortellini, A, Gaillard, VE, Chon, HJ, Pinato, DJ & Ang, C 2022, 'Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratios as Prognostic Biomarkers in Unresectable Hepatocellular Carcinoma Treated with Atezolizumab plus Bevacizumab', Cancers, vol. 14, no. 23, 5834. https://doi.org/10.3390/cancers14235834

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title = "Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratios as Prognostic Biomarkers in Unresectable Hepatocellular Carcinoma Treated with Atezolizumab plus Bevacizumab",

abstract = "Systemic inflammation is a key risk factor for hepatocellular carcinoma (HCC) progression and poor outcomes. Inflammatory markers such as the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) may have prognostic value in HCC treated with standard of care atezolizumab plus bevacizumab (Atezo-Bev). We conducted a multicenter, international retrospective cohort study of patients with unresectable HCC treated with Atezo-Bev to assess the association of NLR and PLR with overall survival (OS), progression-free survival (PFS), and objective response rates. Patients with NLR ≥ 5 had a significantly shorter OS (9.38 vs. 16.79 months, p < 0.001) and PFS (4.90 vs. 7.58 months, p = 0.03) compared to patients with NLR < 5. NLR ≥ 5 was an independent prognosticator of worse OS (HR 2.01, 95% CI 1.22–3.56, p = 0.007) but not PFS. PLR ≥ 300 was also significantly associated with decreased OS (9.38 vs. 15.72 months, p = 0.007) and PFS (3.45 vs. 7.11 months, p = 0.04) compared to PLR < 300, but it was not an independent prognosticator of OS or PFS. NLR and PLR were not associated with objective response or disease control rates. NLR ≥ 5 independently prognosticated worse survival outcomes and is worthy of further study and validation.",

keywords = "NLR, PLR, atezolizumab plus bevacizumab, hepatocellular carcinoma, immunotherapy, inflammatory markers",

author = "Wu, {Yue Linda} and Fulgenzi, {Claudia Angela Maria} and Antonio D{\textquoteright}Alessio and Jaekyung Cheon and Naoshi Nishida and Anwaar Saeed and Brooke Wietharn and Antonella Cammarota and Tiziana Pressiani and Nicola Personeni and Matthias Pinter and Bernhard Scheiner and Lorenz Balcar and Huang, {Yi Hsiang} and Samuel Phen and Naqash, {Abdul Rafeh} and Caterina Vivaldi and Francesca Salani and Gianluca Masi and Dominik Bettinger and Arndt Vogel and Martin Sch{\"o}nlein and {von Felden}, Johann and Kornelius Schulze and Henning Wege and Galle, {Peter R.} and Masatoshi Kudo and Lorenza Rimassa and Singal, {Amit G.} and Rohini Sharma and Alessio Cortellini and Gaillard, {Vincent E.} and Chon, {Hong Jae} and Pinato, {David J.} and Celina Ang",

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month = dec,

doi = "10.3390/cancers14235834",

language = "English (US)",

volume = "14",

journal = "Cancers",

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T1 - Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratios as Prognostic Biomarkers in Unresectable Hepatocellular Carcinoma Treated with Atezolizumab plus Bevacizumab

AU - Wu, Yue Linda

AU - Fulgenzi, Claudia Angela Maria

AU - D’Alessio, Antonio

AU - Cheon, Jaekyung

AU - Nishida, Naoshi

AU - Saeed, Anwaar

AU - Wietharn, Brooke

AU - Cammarota, Antonella

AU - Pressiani, Tiziana

AU - Personeni, Nicola

AU - Pinter, Matthias

AU - Scheiner, Bernhard

AU - Balcar, Lorenz

AU - Huang, Yi Hsiang

AU - Phen, Samuel

AU - Naqash, Abdul Rafeh

AU - Vivaldi, Caterina

AU - Salani, Francesca

AU - Masi, Gianluca

AU - Bettinger, Dominik

AU - Vogel, Arndt

AU - Schönlein, Martin

AU - von Felden, Johann

AU - Schulze, Kornelius

AU - Wege, Henning

AU - Galle, Peter R.

AU - Kudo, Masatoshi

AU - Rimassa, Lorenza

AU - Singal, Amit G.

AU - Sharma, Rohini

AU - Cortellini, Alessio

AU - Gaillard, Vincent E.

AU - Chon, Hong Jae

AU - Pinato, David J.

AU - Ang, Celina

PY - 2022/12

Y1 - 2022/12

N2 - Systemic inflammation is a key risk factor for hepatocellular carcinoma (HCC) progression and poor outcomes. Inflammatory markers such as the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) may have prognostic value in HCC treated with standard of care atezolizumab plus bevacizumab (Atezo-Bev). We conducted a multicenter, international retrospective cohort study of patients with unresectable HCC treated with Atezo-Bev to assess the association of NLR and PLR with overall survival (OS), progression-free survival (PFS), and objective response rates. Patients with NLR ≥ 5 had a significantly shorter OS (9.38 vs. 16.79 months, p < 0.001) and PFS (4.90 vs. 7.58 months, p = 0.03) compared to patients with NLR < 5. NLR ≥ 5 was an independent prognosticator of worse OS (HR 2.01, 95% CI 1.22–3.56, p = 0.007) but not PFS. PLR ≥ 300 was also significantly associated with decreased OS (9.38 vs. 15.72 months, p = 0.007) and PFS (3.45 vs. 7.11 months, p = 0.04) compared to PLR < 300, but it was not an independent prognosticator of OS or PFS. NLR and PLR were not associated with objective response or disease control rates. NLR ≥ 5 independently prognosticated worse survival outcomes and is worthy of further study and validation.

AB - Systemic inflammation is a key risk factor for hepatocellular carcinoma (HCC) progression and poor outcomes. Inflammatory markers such as the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) may have prognostic value in HCC treated with standard of care atezolizumab plus bevacizumab (Atezo-Bev). We conducted a multicenter, international retrospective cohort study of patients with unresectable HCC treated with Atezo-Bev to assess the association of NLR and PLR with overall survival (OS), progression-free survival (PFS), and objective response rates. Patients with NLR ≥ 5 had a significantly shorter OS (9.38 vs. 16.79 months, p < 0.001) and PFS (4.90 vs. 7.58 months, p = 0.03) compared to patients with NLR < 5. NLR ≥ 5 was an independent prognosticator of worse OS (HR 2.01, 95% CI 1.22–3.56, p = 0.007) but not PFS. PLR ≥ 300 was also significantly associated with decreased OS (9.38 vs. 15.72 months, p = 0.007) and PFS (3.45 vs. 7.11 months, p = 0.04) compared to PLR < 300, but it was not an independent prognosticator of OS or PFS. NLR and PLR were not associated with objective response or disease control rates. NLR ≥ 5 independently prognosticated worse survival outcomes and is worthy of further study and validation.

KW - NLR

KW - PLR

KW - atezolizumab plus bevacizumab

KW - hepatocellular carcinoma

KW - immunotherapy

KW - inflammatory markers

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DO - 10.3390/cancers14235834

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Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratios as Prognostic Biomarkers in Unresectable Hepatocellular Carcinoma Treated with Atezolizumab plus Bevacizumab

Abstract

Keywords

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