  Citation: Lo, Y.T.; Lim, V.Y.; Ng, M.; Tan,Y.H.; Chiang, J.; Chang, E.W.Y.; Chan, J.Y.; Poon, E.Y.L.; Somasundaram, N.; Bin Harunal Rashid, M.F.; et al. A Prognostic Model Using Post-Steroid Neutrophil-Lymphocyte Ratio Predicts Overall Survival in Primary Central Nervous System Lymphoma. Cancers 2022, 14, 1818. https:// doi.org/10.3390/cancers14071818 Academic Editor: Pier Luigi Zinzani Received: 23 February 2022 Accepted: 1 April 2022 Published: 3 April 2022 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). cancers Article A Prognostic Model Using Post-Steroid Neutrophil-Lymphocyte Ratio Predicts Overall Survival in Primary Central Nervous System Lymphoma Yu Tung Lo 1,2 , Vivian Yujing Lim 3 , Melissa Ng 4 , Ya Hwee Tan 5 , Jianbang Chiang 5 , Esther Wei Yin Chang 5 , Jason Yongsheng Chan 5,6 , Eileen Yi Ling Poon 5 , Nagavalli Somasundaram 5,6 , Mohamad Farid Bin Harunal Rashid 5,6 , Miriam Tao 5,6 , Soon Thye Lim 5,6 and Valerie Shiwen Yang 3,5,6, * 1 Department of Neurosurgery, National Neuroscience Institute, 11 Jalan Tan Tock Seng, Singapore 308433, Singapore; yutung.lo@mohh.com.sg 2 Department of Neurosurgery, Singapore General Hospital, Outram Road, Singapore 169608, Singapore 3 Translational Precision Oncology Lab, Institute of Molecular and Cell Biology (IMCB), A*STAR, 61 Biopolis Dr, Proteos, Singapore 138673, Singapore; limvyj@imcb.a-star.edu.sg 4 Singapore Immunology Network (SIgN), A*STAR, 8A Biomedical Grove, Immunos, Singapore 138648, Singapore; melissa_ng@immunol.a-star.edu.sg 5 Division of Medical Oncology, National Cancer Centre Singapore, 11 Hospital Crescent, Singapore 169610, Singapore; tan.ya.hwee@singhealth.com.sg (Y.H.T.); chiang.jianbang@singhealth.com.sg (J.C.); esther.chang.w.y@singhealth.com.sg (E.W.Y.C.); jason.chan.y.s@singhealth.com.sg (J.Y.C.); eileen.poon.y.l@singhealth.com.sg (E.Y.L.P.); nagavalli.somasundaram@singhealth.com.sg (N.S.); mohamad.farid@singhealth.com.sg (M.F.B.H.R.); miriam.tao@singhealth.com.sg (M.T.); lim.soon.thye@singhealth.com.sg (S.T.L.) 6 Oncology Academic Clinical Program, Duke-NUS Medical School, 8 College Road, Singapore 169857, Singapore * Correspondence: valerie.yang.s.w@singhealth.com.sg Simple Summary: Hematological indices such as neutrophil-lymphocyte ratio (NLR) have been found to be prognostic for survival outcomes, with higher NLR portending a worse prognosis in primary central nervous system lymphomas (PCNSLs) and other cancers. However, corticosteroids, commonly used for reducing cerebral edema, as well as being a part of systemic treatment, subse- quently alter the balance of neutrophil and lymphocyte composition in the peripheral circulation. We hypothesized that the response to corticosteroids may correlate with the response of PCNSL to systemic treatment and survival. We, therefore, investigated the NLR before and after steroids, and found that higher post-steroid NLR was paradoxically correlated with better survival. We thus developed a new decision-tree-based prognostic score using age, post-steroid NLR and pre-steroid NLR, and showed that it stratified patients into three risk profiles that predicted overall survival with good discrimination and calibration in patient cohorts across two different centers. Abstract: Background: Ratios of differential blood counts (hematological indices, HIs) had been identified as prognostic variables in various cancers. In primary central nervous system lymphomas (PCNSLs), higher baseline neutrophil-lymphocyte ratio (NLR) in particular was found to portend a worse overall survival. However, it was often observed that differential counts shift drastically following steroid administration. Moreover, steroids are an important part of the arsenal against PCNSL due to its potent lymphotoxic effects. We showed that the effect of steroids on differential blood cell counts and HIs could be an early biomarker for subsequent progression-free (PFS) and overall survival (OS). Methods: This study retrospectively identified all adult patients who received a brain biopsy from 2008 to 2019 and had histologically confirmed PCNSL, and included only those who received chemoimmunotherapy, with documented use of corticosteroids prior to treatment induction. Different blood cell counts and HIs were calculated at three time-points: baseline (pre steroid), pre chemoimmunotherapy (post steroid) and post chemoimmunotherapy. Tumor progression and survival data were collected and analyzed through Kaplan–Meier estimates and Cox regression. We then utilized selected variables found to be significant on Kaplan–Meier analysis to generate a Cancers 2022, 14, 1818. https://doi.org/10.3390/cancers14071818 https://www.mdpi.com/journal/cancers