1. The Systemic Inflammatory Response Identifies Patients with Adverse Clinical Outcome from Immunotherapy in Hepatocellular Carcinoma
- Author
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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, and David J. Pinato
- Subjects
Cancer Research ,Oncology ,Hepatology ,platelet-lymphocyte ratio ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,hepatocellular carcinoma ,prognostic nutritional index ,neutrophil-lymphocyte ratio ,inflammatory biomarkers ,Article ,RC254-282 - Abstract
Simple Summary The investigation of predictive and prognostic markers is pivotal in patients affected by hepatocellular carcinoma treated with immune-checkpoint-inhibitors. Inflammation has a central role in hepatocellular carcinoma development and progression; however, its role in influencing outcomes in the context of immunotherapy has not been fully elucidated yet. In the following study, we investigated the prognostic role of bloods derived inflammatory markers and we found that they predict survival and response of patients treated with immunotherapy for advanced 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 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 < 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.
- Published
- 2022