A Novel Prognostic Marker for Primary CNS Lymphoma: Lactate Dehydrogenase-to-Lymphocyte Ratio Improves Stratification of Patients Within the Low and Intermediate MSKCC Risk Groups

Yuting Gao; Li Wei; Seok Jin Kim; Liang Wang; Yingzhi He; Yanfang Zheng; Luca Bertero; Alessia Pellerino; Paola Cassoni; Luca Tamagnone; Prochazka Katharina Theresa; Alexander Deutsch; Huien Zhan; Jing Lai; Yao Wang; Hua You

doi:10.3389/fonc.2021.696147

A Novel Prognostic Marker for Primary CNS Lymphoma: Lactate Dehydrogenase-to-Lymphocyte Ratio Improves Stratification of Patients Within the Low and Intermediate MSKCC Risk Groups

Front Oncol. 2021 Aug 3:11:696147. doi: 10.3389/fonc.2021.696147. eCollection 2021.

Authors

Yuting Gao¹, Li Wei^{1

2}, Seok Jin Kim³, Liang Wang⁴, Yingzhi He⁵, Yanfang Zheng^{1

6}, Luca Bertero⁷, Alessia Pellerino⁸, Paola Cassoni⁷, Luca Tamagnone^{9

10}, Prochazka Katharina Theresa¹¹, Alexander Deutsch¹¹, Huien Zhan¹², Jing Lai¹², Yao Wang¹, Hua You¹

Affiliations

¹ Department of Oncology, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, China.
² NHC Key Laboratory of Birth Defects and Reproductive Health, Chongqing Population and Family Planning Science and Technology Research Institute, Chongqing, China.
³ Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
⁴ Department of Hematology, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
⁵ Department of Hematology, ZhuJiang Hospital of Southern Medical University, Guangzhou, China.
⁶ Department of Oncology, ZhuJiang Hospital of Southern Medical University, Guangzhou, China.
⁷ Pathology Unit, Department of Medical Sciences, University of Turin, Torino, Italy.
⁸ Department of Neuro-Oncology, University and City of Health and Science Hospital, Torino, Italy.
⁹ Università Cattolica del Sacro Cuore, Department of Life Sciences and Public Health, Rome, Italy.
¹⁰ Fondazione Policlinico Universitario "A. Gemelli"- IRCCS, Rome, Italy.
¹¹ Clinical Department of Hematology, Medical University of Graz, Graz, Austria.
¹² Department of Hematology, The First Affiliated Hospital of Jinan University, Guangzhou, China.

Abstract

Background: Primary central nervous system lymphoma (PCNSL) is a highly aggressive and rare extranodal non-Hodgkin lymphoma (NHL). The MSKCC and the IELSG scores represent the most widely used prognostic models, but many changes have occurred in therapeutic protocols since their development. Moreover, many PCNSL patients cannot be classified using the IELSG score. We thus aimed to create a novel, effective and feasible prognostic model for PCNSL.

Methods: We included 248 PCNSL patients diagnosed with PCNSL. Our primary endpoint was the overall survival (OS) and we used the receiver operating characteristic (ROC) analysis to determine the optimal prognostic cut-off value for LLR (lactate dehydrogenase-to-lymphocyte ratio), neutrophil-to-lymphocyte ratio (NLR) and derived neutrophil-to-lymphocyte ratio (dNLR). Variable associated with OS were evaluated by univariate and multivariate analyses. 124 out of 248 patients were randomly selected as the internal validation cohort.

Results: By univariate analysis, an age >60 years, Eastern Cooperative Oncology Group performance status (ECOG PS) >1, treatment with radiotherapy alone, high-risk groups of Memorial Sloan Kettering Cancer Center (MSKCC) score, NLR >4.74, dNLR >3.29, and LLR >166.8 were significantly associated with a worse OS. By multivariate analysis, the MSKCC score and LLR were confirmed as independent prognostic parameters for poorer OS. OS, however, was not significantly different between low- and intermediate-risk groups according to the MSKCC score, while LLR proved to be prognostically relevant and was thus used to develop a novel, effective three-tier PCNSL scoring system. Of 124 patients, 84 patients with survival data and LLR data were successfully validated by newly established PCNSL LLR scoring system.

Conclusions: In the present study, we demonstrate that a high LLR represents an independent unfavorable prognostic parameter in PCNSL patients which can be integrated into an effective prognostic model.

Keywords: Memorial Sloan Kettering Cancer Center (MSKCC) score; lactate dehydrogenase-to-lymphocyte ratio; neutrophil-to-lymphocyte ratio; primary central nervous system lymphoma; prognostic parameter.