The systemic inflammatory response identifies patients with adverse clinical outcome from immunotherapy in hepatocellular carcinoma

Ambreen Muhammed; Claudia Angela Maria Fulgenzi; Sirish Dharmapuri; Matthias Pinter; Lorenz Balcar; Bernhard Scheiner; Thomas U. Marron; Tomi Jun; Anwaar Saeed; Hannah Hildebrand; Mahvish Muzaffar; Musharraf Navaid; Abdul Rafeh Naqash; Anuhya Gampa; Umut Ozbek; Junk Yi Lin; Ylenia Perone; Bruno Vincenzi; Marianna Silletta; Anjana Pillai; Yinghong Wang; Uqba Khan; Yi Hsiang Huang; Dominik Bettinger; Yehia I. Abugabal; Ahmed Kaseb; Tiziana Pressiani; Nicola Personeni; Lorenza Rimassa; Naoshi Nishida; Luca Di Tommaso; Masatoshi Kudo; Arndt Vogel; Francesco A. Mauri; Alessio Cortellini; Rohini Sharma; Antonio D’alessio; Celina Ang; David J. Pinato

doi:10.3390/cancers14010186

The systemic inflammatory response identifies patients with adverse clinical outcome from immunotherapy in hepatocellular carcinoma

Ambreen Muhammed
, Claudia Angela Maria Fulgenzi
, Sirish Dharmapuri
, Matthias Pinter
, Lorenz Balcar
, Bernhard Scheiner
, Thomas U. Marron
, Tomi Jun
, Anwaar Saeed
, Hannah Hildebrand
, Mahvish Muzaffar
, Musharraf Navaid
, Abdul Rafeh Naqash
, Anuhya Gampa
, Umut Ozbek
, Junk Yi Lin
, Ylenia Perone
, Bruno Vincenzi
, Marianna Silletta
, Anjana Pillai

Yinghong Wang, Uqba Khan, Yi Hsiang Huang, Dominik Bettinger, Yehia I. Abugabal, Ahmed Kaseb, Tiziana Pressiani, Nicola Personeni, Lorenza Rimassa, Naoshi Nishida, Luca Di Tommaso, Masatoshi Kudo, Arndt Vogel, Francesco A. Mauri, Alessio Cortellini, Rohini Sharma, Antonio D’alessio, Celina Ang, David J. Pinato

Risultato della ricerca: Contributo su rivista › Articolo in rivista › peer review

Abstract

Systemic inflammation is a hallmark of cancer, and it has a pivotal role in hepatocellular carcinoma (HCC) development and progression. We conducted a retrospective study including 362 patients receiving immune check-point inhibitors (ICIs) across three continents, evaluating the influence of neutrophiles to lymphocytes ratio (NLR), platelets to lymphocytes ratio (PLR), and prognostic nutritional index (PNI) on overall (OS), progression free survival (PFS), and radiologic re-sponses. In our 362 patients treated with immunotherapy, median OS and PFS were 9 and 3.5 months, respectively. Amongst tested inflammatory biomarkers, patients with NLR ≥ 5 had shorter OS (7.7 vs. 17.6 months, p < 0.0001), PFS (2.1 vs. 3.8 months, p = 0.025), and lower objective response rate (ORR) (12% vs. 22%, p = 0.034); similarly, patients with PLR ≥ 300 reported shorter OS (6.4 vs. 16.5 months, p < 0.0001) and PFS (1.8 vs. 3.7 months, p = 0.0006). NLR emerged as independent prognostic factors for OS in univariate and multivariate analysis (HR 1.95, 95%CI 1.45–2.64, p < 0.001; HR 1.73, 95%CI 1.23–2.42, p = 0.002) and PLR remained an independent prognostic factor for both OS and PFS in multivariate analysis (HR 1.60, 95%CI 1.6–2.40, p = 0.020; HR 1.99, 95%CI 1.11–3.49, p = 0.021). Systemic inflammation measured by NLR and PLR is an independent negative prognostic factor in HCC patients undergoing ICI therapy. Further studies are required to understand the biological mechanisms underlying this association and to investigate the predictive significance of circulating inflammatory biomarkers in HCC patients treated with ICIs.

Lingua originale	Inglese
Numero di articolo	186
Rivista	Cancers
Volume	14
Numero di pubblicazione	1
DOI	https://doi.org/10.3390/cancers14010186
Stato di pubblicazione	Pubblicato - 1 gen 2022
Pubblicato esternamente	Sì

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Muhammed, A., Fulgenzi, C. A. M., Dharmapuri, S., Pinter, M., Balcar, L., Scheiner, B., Marron, T. U., Jun, T., Saeed, A., Hildebrand, H., Muzaffar, M., Navaid, M., Naqash, A. R., Gampa, A., Ozbek, U., Lin, J. Y., Perone, Y., Vincenzi, B., Silletta, M., ... Pinato, D. J. (2022). The systemic inflammatory response identifies patients with adverse clinical outcome from immunotherapy in hepatocellular carcinoma. Cancers, 14(1), Articolo 186. https://doi.org/10.3390/cancers14010186

@article{cc138b5476d742afa4112e15a1c581dd,

title = "The systemic inflammatory response identifies patients with adverse clinical outcome from immunotherapy in hepatocellular carcinoma",

abstract = "Systemic inflammation is a hallmark of cancer, and it has a pivotal role in hepatocellular carcinoma (HCC) development and progression. We conducted a retrospective study including 362 patients receiving immune check-point inhibitors (ICIs) across three continents, evaluating the influence of neutrophiles to lymphocytes ratio (NLR), platelets to lymphocytes ratio (PLR), and prognostic nutritional index (PNI) on overall (OS), progression free survival (PFS), and radiologic re-sponses. In our 362 patients treated with immunotherapy, median OS and PFS were 9 and 3.5 months, respectively. Amongst tested inflammatory biomarkers, patients with NLR ≥ 5 had shorter OS (7.7 vs. 17.6 months, p < 0.0001), PFS (2.1 vs. 3.8 months, p = 0.025), and lower objective response rate (ORR) (12\% vs. 22\%, p = 0.034); similarly, patients with PLR ≥ 300 reported shorter OS (6.4 vs. 16.5 months, p < 0.0001) and PFS (1.8 vs. 3.7 months, p = 0.0006). NLR emerged as independent prognostic factors for OS in univariate and multivariate analysis (HR 1.95, 95\%CI 1.45–2.64, p < 0.001; HR 1.73, 95\%CI 1.23–2.42, p = 0.002) and PLR remained an independent prognostic factor for both OS and PFS in multivariate analysis (HR 1.60, 95\%CI 1.6–2.40, p = 0.020; HR 1.99, 95\%CI 1.11–3.49, p = 0.021). Systemic inflammation measured by NLR and PLR is an independent negative prognostic factor in HCC patients undergoing ICI therapy. Further studies are required to understand the biological mechanisms underlying this association and to investigate the predictive significance of circulating inflammatory biomarkers in HCC patients treated with ICIs.",

keywords = "Hepatocellular carcinoma, Inflammatory biomarkers, Neutrophil-lymphocyte ratio, Platelet-lymphocyte ratio, Prognostic nutritional index",

author = "Ambreen Muhammed and Fulgenzi, \{Claudia Angela Maria\} and Sirish Dharmapuri and Matthias Pinter and Lorenz Balcar and Bernhard Scheiner and Marron, \{Thomas U.\} and Tomi Jun and Anwaar Saeed and Hannah Hildebrand and Mahvish Muzaffar and Musharraf Navaid and Naqash, \{Abdul Rafeh\} and Anuhya Gampa and Umut Ozbek and Lin, \{Junk Yi\} and Ylenia Perone and Bruno Vincenzi and Marianna Silletta and Anjana Pillai and Yinghong Wang and Uqba Khan and Huang, \{Yi Hsiang\} and Dominik Bettinger and Abugabal, \{Yehia I.\} and Ahmed Kaseb and Tiziana Pressiani and Nicola Personeni and Lorenza Rimassa and Naoshi Nishida and Tommaso, \{Luca Di\} and Masatoshi Kudo and Arndt Vogel and Mauri, \{Francesco A.\} and Alessio Cortellini and Rohini Sharma and Antonio D{\textquoteright}alessio and Celina Ang and Pinato, \{David J.\}",

note = "Publisher Copyright: {\textcopyright} 2021 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2022",

month = jan,

day = "1",

doi = "10.3390/cancers14010186",

language = "English",

volume = "14",

journal = "Cancers",

issn = "2072-6694",

publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

number = "1",

}

Muhammed, A, Fulgenzi, CAM, Dharmapuri, S, Pinter, M, Balcar, L, Scheiner, B, Marron, TU, Jun, T, Saeed, A, Hildebrand, H, Muzaffar, M, Navaid, M, Naqash, AR, Gampa, A, Ozbek, U, Lin, JY, Perone, Y, Vincenzi, B, Silletta, M, Pillai, A, Wang, Y, Khan, U, Huang, YH, Bettinger, D, Abugabal, YI, Kaseb, A, Pressiani, T, Personeni, N, Rimassa, L, Nishida, N, Tommaso, LD, Kudo, M, Vogel, A, Mauri, FA, Cortellini, A, Sharma, R, D’alessio, A, Ang, C & Pinato, DJ 2022, 'The systemic inflammatory response identifies patients with adverse clinical outcome from immunotherapy in hepatocellular carcinoma', Cancers, vol. 14, n. 1, 186. https://doi.org/10.3390/cancers14010186

TY - JOUR

T1 - The systemic inflammatory response identifies patients with adverse clinical outcome from immunotherapy in hepatocellular carcinoma

AU - Muhammed, Ambreen

AU - Fulgenzi, Claudia Angela Maria

AU - Dharmapuri, Sirish

AU - Pinter, Matthias

AU - Balcar, Lorenz

AU - Scheiner, Bernhard

AU - Marron, Thomas U.

AU - Jun, Tomi

AU - Saeed, Anwaar

AU - Hildebrand, Hannah

AU - Muzaffar, Mahvish

AU - Navaid, Musharraf

AU - Naqash, Abdul Rafeh

AU - Gampa, Anuhya

AU - Ozbek, Umut

AU - Lin, Junk Yi

AU - Perone, Ylenia

AU - Vincenzi, Bruno

AU - Silletta, Marianna

AU - Pillai, Anjana

AU - Wang, Yinghong

AU - Khan, Uqba

AU - Huang, Yi Hsiang

AU - Bettinger, Dominik

AU - Abugabal, Yehia I.

AU - Kaseb, Ahmed

AU - Pressiani, Tiziana

AU - Personeni, Nicola

AU - Rimassa, Lorenza

AU - Nishida, Naoshi

AU - Tommaso, Luca Di

AU - Kudo, Masatoshi

AU - Vogel, Arndt

AU - Mauri, Francesco A.

AU - Cortellini, Alessio

AU - Sharma, Rohini

AU - D’alessio, Antonio

AU - Ang, Celina

AU - Pinato, David J.

PY - 2022/1/1

Y1 - 2022/1/1

N2 - Systemic inflammation is a hallmark of cancer, and it has a pivotal role in hepatocellular carcinoma (HCC) development and progression. We conducted a retrospective study including 362 patients receiving immune check-point inhibitors (ICIs) across three continents, evaluating the influence of neutrophiles to lymphocytes ratio (NLR), platelets to lymphocytes ratio (PLR), and prognostic nutritional index (PNI) on overall (OS), progression free survival (PFS), and radiologic re-sponses. In our 362 patients treated with immunotherapy, median OS and PFS were 9 and 3.5 months, respectively. Amongst tested inflammatory biomarkers, patients with NLR ≥ 5 had shorter OS (7.7 vs. 17.6 months, p < 0.0001), PFS (2.1 vs. 3.8 months, p = 0.025), and lower objective response rate (ORR) (12% vs. 22%, p = 0.034); similarly, patients with PLR ≥ 300 reported shorter OS (6.4 vs. 16.5 months, p < 0.0001) and PFS (1.8 vs. 3.7 months, p = 0.0006). NLR emerged as independent prognostic factors for OS in univariate and multivariate analysis (HR 1.95, 95%CI 1.45–2.64, p < 0.001; HR 1.73, 95%CI 1.23–2.42, p = 0.002) and PLR remained an independent prognostic factor for both OS and PFS in multivariate analysis (HR 1.60, 95%CI 1.6–2.40, p = 0.020; HR 1.99, 95%CI 1.11–3.49, p = 0.021). Systemic inflammation measured by NLR and PLR is an independent negative prognostic factor in HCC patients undergoing ICI therapy. Further studies are required to understand the biological mechanisms underlying this association and to investigate the predictive significance of circulating inflammatory biomarkers in HCC patients treated with ICIs.

AB - Systemic inflammation is a hallmark of cancer, and it has a pivotal role in hepatocellular carcinoma (HCC) development and progression. We conducted a retrospective study including 362 patients receiving immune check-point inhibitors (ICIs) across three continents, evaluating the influence of neutrophiles to lymphocytes ratio (NLR), platelets to lymphocytes ratio (PLR), and prognostic nutritional index (PNI) on overall (OS), progression free survival (PFS), and radiologic re-sponses. In our 362 patients treated with immunotherapy, median OS and PFS were 9 and 3.5 months, respectively. Amongst tested inflammatory biomarkers, patients with NLR ≥ 5 had shorter OS (7.7 vs. 17.6 months, p < 0.0001), PFS (2.1 vs. 3.8 months, p = 0.025), and lower objective response rate (ORR) (12% vs. 22%, p = 0.034); similarly, patients with PLR ≥ 300 reported shorter OS (6.4 vs. 16.5 months, p < 0.0001) and PFS (1.8 vs. 3.7 months, p = 0.0006). NLR emerged as independent prognostic factors for OS in univariate and multivariate analysis (HR 1.95, 95%CI 1.45–2.64, p < 0.001; HR 1.73, 95%CI 1.23–2.42, p = 0.002) and PLR remained an independent prognostic factor for both OS and PFS in multivariate analysis (HR 1.60, 95%CI 1.6–2.40, p = 0.020; HR 1.99, 95%CI 1.11–3.49, p = 0.021). Systemic inflammation measured by NLR and PLR is an independent negative prognostic factor in HCC patients undergoing ICI therapy. Further studies are required to understand the biological mechanisms underlying this association and to investigate the predictive significance of circulating inflammatory biomarkers in HCC patients treated with ICIs.

KW - Hepatocellular carcinoma

KW - Inflammatory biomarkers

KW - Neutrophil-lymphocyte ratio

KW - Platelet-lymphocyte ratio

KW - Prognostic nutritional index

UR - https://www.scopus.com/pages/publications/85122032421

U2 - 10.3390/cancers14010186

DO - 10.3390/cancers14010186

M3 - Article

SN - 2072-6694

VL - 14

JO - Cancers

JF - Cancers

IS - 1

M1 - 186

ER -

The systemic inflammatory response identifies patients with adverse clinical outcome from immunotherapy in hepatocellular carcinoma

Abstract

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