Cancers (Dec 2021)
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
Affiliations
- Ambreen Muhammed
- Department of Surgery & Cancer, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0HS, UK
- Claudia Angela Maria Fulgenzi
- Department of Surgery & Cancer, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0HS, UK
- Sirish Dharmapuri
- Department of Medicine, Division of Hematology/Oncology, Tisch Cancer Institute, Mount Sinai Hospital, New York, NY 10029, USA
- Matthias Pinter
- Department of Internal Medicine III, Division of Gastroenterology & Hepatology, Medical University of Vienna, 1090 Vienna, Austria
- Lorenz Balcar
- Department of Internal Medicine III, Division of Gastroenterology & Hepatology, Medical University of Vienna, 1090 Vienna, Austria
- Bernhard Scheiner
- Department of Internal Medicine III, Division of Gastroenterology & Hepatology, Medical University of Vienna, 1090 Vienna, Austria
- Thomas U. Marron
- Department of Medicine, Division of Hematology/Oncology, Tisch Cancer Institute, Mount Sinai Hospital, New York, NY 10029, USA
- Tomi Jun
- Department of Medicine, Division of Hematology/Oncology, Tisch Cancer Institute, Mount Sinai Hospital, New York, NY 10029, USA
- Anwaar Saeed
- Division of Medical Oncology, Department of Medicine, Kansas University Cancer Center, Westwood, KS 66205, USA
- Hannah Hildebrand
- Division of Medical Oncology, Department of Medicine, Kansas University Cancer Center, Westwood, KS 66205, USA
- Mahvish Muzaffar
- Division of Hematology/Oncology, East Carolina University, 600 Moye Boulevard, Greenville, NC 27834, USA
- Musharraf Navaid
- Division of Hematology/Oncology, East Carolina University, 600 Moye Boulevard, Greenville, NC 27834, USA
- Abdul Rafeh Naqash
- Division of Hematology/Oncology, East Carolina University, 600 Moye Boulevard, Greenville, NC 27834, USA
- Anuhya Gampa
- Section of Gastroenterology, Hepatology & Nutrition, The University of Chicago Medicine, 5841 S. Maryland Ave, Chicago, IL 60637, USA
- Umut Ozbek
- Department of Population Health Science and Policy, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
- Junk-Yi Lin
- Department of Population Health Science and Policy, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
- Ylenia Perone
- Department of Surgery & Cancer, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0HS, UK
- Bruno Vincenzi
- Department of Medical Oncology, University Campus Bio-Medico, 00128 Rome, Italy
- Marianna Silletta
- Department of Medical Oncology, University Campus Bio-Medico, 00128 Rome, Italy
- Anjana Pillai
- Section of Gastroenterology, Hepatology & Nutrition, The University of Chicago Medicine, 5841 S. Maryland Ave, Chicago, IL 60637, USA
- Yinghong Wang
- Department of Gastroenterology, Hepatology & Nutrition, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
- Uqba Khan
- Division of Hematology and Oncology, Weill Cornell Medicine/New York Presbyterian Hospital, 1305 York Avenue, Room Y1247, New York, NY 10021, USA
- Yi-Hsiang Huang
- Division of Gastroenterology and Hepatology, Taipei Veterans General Hospital, Institute of Clinical Medicine, National Yang Ming Chiao Tung University School of Medicine, Taipei 11217, Taiwan
- Dominik Bettinger
- Department of Medicine II, Faculty of Medicine, Medical Center University of Freiburg, University of Freiburg, 79106 Freiburg, Germany
- Yehia I. Abugabal
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
- Ahmed Kaseb
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
- Tiziana Pressiani
- Medical Oncology and Hematology Unit, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089 Milan, Italy
- Nicola Personeni
- Medical Oncology and Hematology Unit, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089 Milan, Italy
- Lorenza Rimassa
- Medical Oncology and Hematology Unit, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089 Milan, Italy
- Naoshi Nishida
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka-Sayama, Osaka 589-8511, Japan
- Luca Di Tommaso
- Humanitas Clinical and Research Center IRCCS, Pathology Unit, 20089 Rozzano, Italy
- Masatoshi Kudo
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka-Sayama, Osaka 589-8511, Japan
- Arndt Vogel
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, 30625 Hannover, Germany
- Francesco A. Mauri
- Department of Surgery & Cancer, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0HS, UK
- Alessio Cortellini
- Department of Surgery & Cancer, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0HS, UK
- Rohini Sharma
- Department of Surgery & Cancer, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0HS, UK
- Antonio D’Alessio
- Department of Surgery & Cancer, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0HS, UK
- Celina Ang
- Department of Medicine, Division of Hematology/Oncology, Tisch Cancer Institute, Mount Sinai Hospital, New York, NY 10029, USA
- David J. Pinato
- Department of Surgery & Cancer, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0HS, UK
- DOI
- https://doi.org/10.3390/cancers14010186
- Journal volume & issue
-
Vol. 14,
no. 1
p. 186
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 responses. 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 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 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 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
