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Chernov AN, Skliar SS, Yatskou MM, Skakun VV, Pyurveev SS, Batotsyrenova EG, Zheregelya SN, Liu G, Kashuro VA, Ivanov DO, Ivanov SD. Glioblastoma and Blood Microenvironment Predictive Model for Life Expectancy of Patients. Biomedicines 2025; 13:1040. [PMID: 40426873 DOI: 10.3390/biomedicines13051040] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2025] [Revised: 04/19/2025] [Accepted: 04/22/2025] [Indexed: 05/29/2025] Open
Abstract
Background: Glioblastoma multiforme (GBM) is a very malignant brain tumor. GBM exhibits cellular and molecular heterogeneity that can be exploited to improve patient outcomes by individually tailoring chemotherapy regimens. Objective: Our objective was to develop a predictive model of the life expectancy of GBM patients using data on tumor cells' sensitivity to chemotherapy drugs, as well as the levels of blood cells and proteins forming the tumor microenvironment. Methods: The investigation included 31 GBM patients from the Almazov Medical Research Centre (Saint Petersburg, Russia). The cytotoxic effects of chemotherapy drugs on GBM cells were studied by an MTT test using a 50% inhibitory concentration (IC50). We analyzed the data with life expectancy by a one-way ANOVA, principal component analysis (PCA), ROC, and Kaplan-Meier survival tests using GraphPad Prism and Statistica 10 software. Results: We determined in vitro the IC50 of six chemotherapy drugs for GBM and 32 clinical and biochemical blood indicators for these patients. This model includes an assessment of only three parameters: IC50 of tumor cells to carboplatin (CARB) higher than 4.115 μg/mL, as well as levels of band neutrophils (NEUT-B) below 2.5% and total protein (TP) above 64.5 g/L in the blood analysis, which allows predicting with 83.3% probability (sensitivity) the life expectancy of patients for 15 months or more. In opposite, a change in these parameters-CARB above 4115 μg/mL, NEUT-B below 2.5%, and TP above 64.5 g/L-predict with 83.3% probability (specificity) no survival rate of GBM patients for more than 15 months. The relative risk for CARB was 6.41 (95 CI: 4.37-8.47, p = 0.01); for NEUT-B, the RR was 0.40 (95 CI: 0.26-0.87, p = 0.09); and for TP, it was 2.88 (95 CI: 1.57-4.19, p = 0.09). Overall, the model predicted the risk of developing a positive event (an outcome with a life expectancy more than 10 months) eight times (95 CI 6.34-9.66, p < 0.01). Cross k-means validation on three clusters (n = 10) of the model showed that its average accuracy (sensitivity and specificity) for cluster 1 was 74.98%; for cluster 2, it was 66.7%; and for cluster 3, it was 60.0%. At the same time, the differences between clusters 1, 2, and 3 were not significant. The results of the Sobel test show that there are no interactions between the components of the model, and each component is an independent factor influencing the event (life expectancy, survival) of GBM patients. Conclusions: A simple predictive model for GBM patients' life expectancy has been developed using statistical analysis methods.
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Affiliation(s)
- Alexander N Chernov
- Biological Chemistry Department, Federal State Budgetary Educational Institution of Higher Education Saint Petersburg State Pediatric Medical University of the Ministry of Health of Russia, 194100 Saint Petersburg, Russia
- Department of General Pathology and Pathophysiology, Federal State Budgetary Institution of Science "Institute of Experimental Medicine", 197022 Saint Petersburg, Russia
| | - Sofia S Skliar
- Laboratory of Neurooncology of Polenov Neurosurgical Institute, Almazov National Medical Research Centre, 197341 Saint Petersburg, Russia
| | - Mikalai M Yatskou
- Department of System Analysis and Computer Modeling, Belarussian State University, 220030 Minsk, Belarus
| | - Victor V Skakun
- Department of System Analysis and Computer Modeling, Belarussian State University, 220030 Minsk, Belarus
| | - Sarng S Pyurveev
- Biological Chemistry Department, Federal State Budgetary Educational Institution of Higher Education Saint Petersburg State Pediatric Medical University of the Ministry of Health of Russia, 194100 Saint Petersburg, Russia
- Department of General Pathology and Pathophysiology, Federal State Budgetary Institution of Science "Institute of Experimental Medicine", 197022 Saint Petersburg, Russia
| | - Ekaterina G Batotsyrenova
- Biological Chemistry Department, Federal State Budgetary Educational Institution of Higher Education Saint Petersburg State Pediatric Medical University of the Ministry of Health of Russia, 194100 Saint Petersburg, Russia
| | - Sergey N Zheregelya
- Biological Chemistry Department, Federal State Budgetary Educational Institution of Higher Education Saint Petersburg State Pediatric Medical University of the Ministry of Health of Russia, 194100 Saint Petersburg, Russia
| | - Guodong Liu
- Department of Neurosurgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
| | - Vadim A Kashuro
- Biological Chemistry Department, Federal State Budgetary Educational Institution of Higher Education Saint Petersburg State Pediatric Medical University of the Ministry of Health of Russia, 194100 Saint Petersburg, Russia
- Department of Maxillofacial Surgery and Surgical Dentistry, Medical Institute of Saint Petersburg State University, 199034 Saint Petersburg, Russia
- Department of Anatomy and Physiology of Humans and Animals, Herzen State Pedagogical University of Russia, 191186 Saint Petersburg, Russia
| | - Dmitry O Ivanov
- Biological Chemistry Department, Federal State Budgetary Educational Institution of Higher Education Saint Petersburg State Pediatric Medical University of the Ministry of Health of Russia, 194100 Saint Petersburg, Russia
| | - Sergey D Ivanov
- Federal State Budgetary Institution "National Medical Research Center of Oncology named after N.N. Petrov" of the Ministry of Health of the Russian Federation, 197758 Saint Petersburg, Russia
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Song K, Chen C, Xu H, Chen L, Xu H, Han X, Chen H, Qin Z. Prediction of Survival in the Elderly Patients with Glioblastoma using Cumulative Inflammatory Markers Score. J Neurol Surg B Skull Base 2025; 86:98-105. [PMID: 39881741 PMCID: PMC11774615 DOI: 10.1055/s-0044-1779050] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2023] [Accepted: 12/21/2023] [Indexed: 01/31/2025] Open
Abstract
Objectives This retrospective study aimed to explore the prognostic effect of cumulative score based on neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and fibrinogen in older adults diagnosed with glioblastoma (GBM). Design Retrospective study. Setting Huashan Hospital. Participants Patients aged over 60 years and diagnosed with GBM between 2010 and 2017. Main Outcome Measures Results of preoperative routine biochemistry and coagulation blood examinations were reviewed from medical records. Overall survival (OS) was considered a period from first resection surgery until death. Progression-free survival (PFS) was considered a period from initial operation until the date of tumor progression demonstrated in brain magnetic resonance imaging or death from any cause. If no event occurred, the last follow-up appointment was the end of the observation for OS or PFS. The Kaplan-Meier method was used to evaluate survival curves, and prognostic factors were analyzed by the Cox proportional hazards model. Results A total of 289 patients were included. Patients with higher levels of fibrinogen, NLR, and PLR had significantly shorter median OS ( p = 0.001, p = 0.016, and p = 0.002, respectively) and PFS ( p = 0.004, p = 0.022, and p = 0.009, respectively) compared with those with lower levels. Multivariate analyses showed a significant association between higher F-NLR-PLR score and reduced OS (adjusted hazard ratios [aHRs]: 1.356, 95% confidence interval [CI] 1.009-1.822 for scores 1-2 compared with 0; 5.974, 95% CI 2.811-12.698 for score 3 compared with 0). Similarly, a significant association between higher F-NLR-PLR score and reduced PFS was observed (aHR: 1.428, 95% CI 1.066-1.912 for scores 1-2 compared with 0; aHR: 2.860, 95% CI 1.315-6.223 for score 3 compared with 0). Conclusion Higher F-NLR-PLR score is associated with reduced OS and PFS in older adults with GBM, which helps identify patients at high risk and guide the individualized treatment in clinical practice.
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Affiliation(s)
- Kun Song
- Department of Neurosurgery, Huashan Hospital Shanghai Medical College, Fudan University, Shanghai, China
| | - Chunjui Chen
- Department of Neurosurgery, Huashan Hospital Shanghai Medical College, Fudan University, Shanghai, China
| | - Hao Xu
- Department of Neurosurgery, Huashan Hospital Shanghai Medical College, Fudan University, Shanghai, China
| | - Lingchao Chen
- Department of Neurosurgery, Huashan Hospital Shanghai Medical College, Fudan University, Shanghai, China
| | - Hongzhi Xu
- Department of Neurosurgery, Huashan Hospital Shanghai Medical College, Fudan University, Shanghai, China
| | - Xi Han
- Department of Neurosurgery, Huashan Hospital Shanghai Medical College, Fudan University, Shanghai, China
| | - Hong Chen
- Department of Neuropathology, Huashan Hospital Shanghai Medical College, Fudan University, Shanghai, China
| | - Zhiyong Qin
- Department of Neurosurgery, Huashan Hospital Shanghai Medical College, Fudan University, Shanghai, China
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Zhou J, Tan B, Gao F. Prognostic values of combined ratios of white blood cells in glioma: a systematic review and meta-analysis. Neurosurg Rev 2024; 47:831. [PMID: 39477886 DOI: 10.1007/s10143-024-03064-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2024] [Revised: 10/09/2024] [Accepted: 10/18/2024] [Indexed: 11/15/2024]
Abstract
Gliomas, the most prevalent type of neurological tumor, pose a challenging prognosis for patients. Recent studies have underscored the importance of inflammatory markers such as the neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and monocyte/lymphocyte ratio (MLR) in predicting the prognosis of gliomas. We undertook a thorough meta-analysis to elucidate the role of these inflammatory markers in forecasting the prognosis of glioma patients. We extracted hazard ratios (HR) and their corresponding 95% confidence intervals (95% CI) from each study for analysis. To assess heterogeneity and identify influential studies, we conducted sensitivity analysis. Subgroup analysis was performed to investigate sources of heterogeneity, and we employed Egger's test to evaluate publication bias in the meta-analysis. Higher NLR levels were associated with shorter overall survival (HR = 1.46, 95% CI: 1.33-1.60) and progression-free survival (HR = 1.24, 95% CI: 1.04-1.48). There was no significant correlation between PLR levels and overall survival (HR = 1.01, 95% CI: 1.00-1.01) or progression-free survival (HR = 1.00, 95% CI: 0.98-1.02) in glioma patients. Elevated MLR levels were associated with decreased overall survival in glioma patients (HR = 1.78, 95% CI: 1.36-2.34). SII levels did not show any significant association with overall or progression-free survival in glioma patients (HR = 1.00, 95% CI: 0.99-1.01).In the sensitivity analysis, two studies potentially contributed to the instability. Subgroup analyses showed patient population and area were identified as potential sources of heterogeneity. Egger's test showed that there was publication bias in the relationship between NLR and PLR and overall survival (P < 0.05).All randomized controlled models, except for these, were not affected by publication bias. NLR and MLR are two reliable indicators of inflammation in the prognosis of glioma patients; PLR and SII do not have significant value in the prognosis of glioma patients.
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Affiliation(s)
- JiaNuo Zhou
- School of Medicine, LiShui University, LiShui, 323000, Zhejiang, China
| | - Botao Tan
- LiShui University, LiShui, 323000, Zhejiang, China.
| | - Feng Gao
- Department of Neurosurgery, the Affiliated People's Hospital of Ningbo University, Ningbo, 315040, Zhejiang, China.
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Vatankhahan H, Esteki F, Jabalameli MA, Kiani P, Ehtiati S, Movahedpour A, Vakili O, Khatami SH. Electrochemical biosensors for early diagnosis of glioblastoma. Clin Chim Acta 2024; 557:117878. [PMID: 38493942 DOI: 10.1016/j.cca.2024.117878] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2024] [Revised: 03/12/2024] [Accepted: 03/14/2024] [Indexed: 03/19/2024]
Abstract
Glioblastoma (GBM) is a highly aggressive and life-threatening neurological malignancy of predominant astrocyte origin. This type of neoplasm can develop in either the brain or the spine and is also known as glioblastoma multiforme. Although current diagnostic methods such as magnetic resonance imaging (MRI) and positron emission tomography (PET) facilitate tumor location, these approaches are unable to assess disease severity. Furthermore, interpretation of imaging studies requires significant expertise which can have substantial inter-observer variability, thus challenging diagnosis and potentially delaying treatment. In contrast, biosensing systems offer a promising alternative to these traditional approaches. These technologies can continuously monitor specific molecules, providing valuable real-time data on treatment response, and could significantly improve patient outcomes. Among various types of biosensors, electrochemical systems are preferred over other types, as they do not require expensive or complex equipment or procedures and can be made with readily available materials and methods. Moreover, electrochemical biosensors can detect very small amounts of analytes with high accuracy and specificity by using various signal amplification strategies and recognition elements. Considering the advantages of electrochemical biosensors compared to other biosensing methods, we aim to highlight the potential application(s) of these sensors for GBM theranostics. The review's innovative insights are expected to antecede the development of novel biosensors and associated diagnostic platforms, ultimately restructuring GBM detection strategies.
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Affiliation(s)
- Hamid Vatankhahan
- Department of Biochemistry and Clinical Laboratories, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Farnaz Esteki
- Department of Medical Laboratory Sciences, School of Paramedicine, Kashan University of Medical Sciences, Kashan, Iran
| | - Mohammad Amin Jabalameli
- Department of Cell and Molecular Biology, School of Biology, College of Science, University of Tehran, Tehran, Iran
| | - Pouria Kiani
- Department of Clinical Biochemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Sajad Ehtiati
- Department of Clinical Biochemistry, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | | | - Omid Vakili
- Department of Clinical Biochemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran; Autophagy Research Center, Department of Clinical Biochemistry, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
| | - Seyyed Hossein Khatami
- Student Research Committee, Department of Clinical Biochemistry, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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Matsuda R, Hasegawa M, Tamamoto T, Inooka N, Morimoto T, Maeoka R, Nakazawa T, Ochi T, Miyasaka T, Hontsu S, Yamaki K, Miura S, Yamada S, Nishimura F, Nakagawa I, Park YS, Nakase H. Clinical Results and Hematologic Predictors of Linear Accelerator-Based Stereotactic Radiosurgery or Fractionated Stereotactic Radiotherapy for Brain Metastasis in Patients Aged 75 Years or Older: A Retrospective Study. World Neurosurg 2024; 183:e944-e952. [PMID: 38244685 DOI: 10.1016/j.wneu.2024.01.069] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2023] [Revised: 01/11/2024] [Accepted: 01/12/2024] [Indexed: 01/22/2024]
Abstract
OBJECTIVE This study aimed to evaluate prognostic factors including pre-radiosurgical blood count in elderly patients (EPs) with brain metastasis (BM) who were treated using linear accelerator (LINAC)-based stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (fSRT) with a micro-multileaf collimator. METHODS Between January 2011 and November 2021, 101 consecutive EPs with BM were treated by LINAC-based SRS or fSRT using LINAC with a micro-multileaf collimator. EPs were defined as patients aged ≥75 years. RESULTS The tumors originated from the lungs (n = 90; 89.1%), colon (n = 2; 2.0%), and others (n = 9; 8.8%) in these EPs. The median pretreatment Karnofsky Performance Status was 80 (range, 40-100). The median follow-up time was 10 months (range, 0-76), as was the median survival. The 6-month, 1-year, and 2-year survival in the EP group was 58.3%, 43.2%, and 28.5%, respectively. Freedom from local failure at 6 months and 1 and 2 years was 97%, 95%, and 91.5%, respectively. Freedom from distant failure at 6 months and 1 and 2 years in EPs was 70.6%, 59.4%, and 54.2%, respectively. A high neutrophil/lymphocyte ratio >5.33 was an unfavorable predictor of prognosis for EPs with BMs treated with SRS and fSRT (P < 0.001). In the EPs, the prognostic factors associated with prolonged survival in the Cox proportional hazards model were being female and a good pretreatment Karnofsky Performance Status. CONCLUSIONS The findings of our study highlight the efficacy of LINAC-based SRS and fSRT with a micro-multileaf collimator in the treatment of EPs with BMs. Neutrophil/lymphocyte ratio can be an important factor in treatment decisions for EPs with BMs.
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Affiliation(s)
- Ryosuke Matsuda
- Department of Neurosurgery, Nara Medical University, Kashihara, Nara, Japan.
| | - Masatoshi Hasegawa
- Department of Radiation Oncology, Nara Medical University, Kashihara, Nara, Japan
| | - Tetsuro Tamamoto
- Department of Radiation Oncology, Nara Medical University, Kashihara, Nara, Japan; Department of Medical Informatics, Nara Medical University Hospital, Kashihara, Nara, Japan
| | - Nobuyoshi Inooka
- Department of Radiation Oncology, Nara Medical University, Kashihara, Nara, Japan
| | - Takayuki Morimoto
- Department of Neurosurgery, Nara Medical University, Kashihara, Nara, Japan
| | - Ryosuke Maeoka
- Department of Neurosurgery, Nara Medical University, Kashihara, Nara, Japan
| | - Tsutomu Nakazawa
- Department of Neurosurgery, Nara Medical University, Kashihara, Nara, Japan
| | - Tomoko Ochi
- Department of Respiratory Medicine, Nara Medical University, Kashihara, Nara, Japan
| | - Toshiteru Miyasaka
- Department of Respiratory Medicine, Nara Medical University, Kashihara, Nara, Japan
| | - Shigeto Hontsu
- Department of Respiratory Medicine, Nara Medical University, Kashihara, Nara, Japan
| | - Kaori Yamaki
- Department of Radiation Oncology, Nara Medical University, Kashihara, Nara, Japan
| | - Sachiko Miura
- Department of Radiation Oncology, Nara Medical University, Kashihara, Nara, Japan
| | - Shuichi Yamada
- Department of Neurosurgery, Nara Medical University, Kashihara, Nara, Japan
| | - Fumihiko Nishimura
- Department of Neurosurgery, Nara Medical University, Kashihara, Nara, Japan
| | - Ichiro Nakagawa
- Department of Neurosurgery, Nara Medical University, Kashihara, Nara, Japan
| | - Young-Soo Park
- Department of Neurosurgery, Nara Medical University, Kashihara, Nara, Japan
| | - Hiroyuki Nakase
- Department of Neurosurgery, Nara Medical University, Kashihara, Nara, Japan
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Stepanenko AA, Sosnovtseva AO, Valikhov MP, Chernysheva AA, Abramova OV, Pavlov KA, Chekhonin VP. Systemic and local immunosuppression in glioblastoma and its prognostic significance. Front Immunol 2024; 15:1326753. [PMID: 38481999 PMCID: PMC10932993 DOI: 10.3389/fimmu.2024.1326753] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2023] [Accepted: 02/06/2024] [Indexed: 04/07/2024] Open
Abstract
The effectiveness of tumor therapy, especially immunotherapy and oncolytic virotherapy, critically depends on the activity of the host immune cells. However, various local and systemic mechanisms of immunosuppression operate in cancer patients. Tumor-associated immunosuppression involves deregulation of many components of immunity, including a decrease in the number of T lymphocytes (lymphopenia), an increase in the levels or ratios of circulating and tumor-infiltrating immunosuppressive subsets [e.g., macrophages, microglia, myeloid-derived suppressor cells (MDSCs), and regulatory T cells (Tregs)], as well as defective functions of subsets of antigen-presenting, helper and effector immune cell due to altered expression of various soluble and membrane proteins (receptors, costimulatory molecules, and cytokines). In this review, we specifically focus on data from patients with glioblastoma/glioma before standard chemoradiotherapy. We discuss glioblastoma-related immunosuppression at baseline and the prognostic significance of different subsets of circulating and tumor-infiltrating immune cells (lymphocytes, CD4+ and CD8+ T cells, Tregs, natural killer (NK) cells, neutrophils, macrophages, MDSCs, and dendritic cells), including neutrophil-to-lymphocyte ratio (NLR), focus on the immune landscape and prognostic significance of isocitrate dehydrogenase (IDH)-mutant gliomas, proneural, classical and mesenchymal molecular subtypes, and highlight the features of immune surveillance in the brain. All attempts to identify a reliable prognostic immune marker in glioblastoma tissue have led to contradictory results, which can be explained, among other things, by the unprecedented level of spatial heterogeneity of the immune infiltrate and the significant phenotypic diversity and (dys)functional states of immune subpopulations. High NLR is one of the most repeatedly confirmed independent prognostic factors for shorter overall survival in patients with glioblastoma and carcinoma, and its combination with other markers of the immune response or systemic inflammation significantly improves the accuracy of prediction; however, more prospective studies are needed to confirm the prognostic/predictive power of NLR. We call for the inclusion of dynamic assessment of NLR and other blood inflammatory markers (e.g., absolute/total lymphocyte count, platelet-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, systemic immune-inflammation index, and systemic immune response index) in all neuro-oncology studies for rigorous evaluation and comparison of their individual and combinatorial prognostic/predictive significance and relative superiority.
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Affiliation(s)
- Aleksei A. Stepanenko
- Department of Fundamental and Applied Neurobiology, V. P. Serbsky National Medical Research Center of Psychiatry and Narcology, the Ministry of Health of the Russian Federation, Moscow, Russia
- Department of Medical Nanobiotechnology, Institute of Translational Medicine, N. I. Pirogov Russian National Research Medical University, The Ministry of Health of the Russian Federation, Moscow, Russia
| | - Anastasiia O. Sosnovtseva
- Department of Fundamental and Applied Neurobiology, V. P. Serbsky National Medical Research Center of Psychiatry and Narcology, the Ministry of Health of the Russian Federation, Moscow, Russia
- Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia
| | - Marat P. Valikhov
- Department of Fundamental and Applied Neurobiology, V. P. Serbsky National Medical Research Center of Psychiatry and Narcology, the Ministry of Health of the Russian Federation, Moscow, Russia
- Department of Medical Nanobiotechnology, Institute of Translational Medicine, N. I. Pirogov Russian National Research Medical University, The Ministry of Health of the Russian Federation, Moscow, Russia
| | - Anastasia A. Chernysheva
- Department of Fundamental and Applied Neurobiology, V. P. Serbsky National Medical Research Center of Psychiatry and Narcology, the Ministry of Health of the Russian Federation, Moscow, Russia
| | - Olga V. Abramova
- Department of Fundamental and Applied Neurobiology, V. P. Serbsky National Medical Research Center of Psychiatry and Narcology, the Ministry of Health of the Russian Federation, Moscow, Russia
| | - Konstantin A. Pavlov
- Department of Fundamental and Applied Neurobiology, V. P. Serbsky National Medical Research Center of Psychiatry and Narcology, the Ministry of Health of the Russian Federation, Moscow, Russia
| | - Vladimir P. Chekhonin
- Department of Fundamental and Applied Neurobiology, V. P. Serbsky National Medical Research Center of Psychiatry and Narcology, the Ministry of Health of the Russian Federation, Moscow, Russia
- Department of Medical Nanobiotechnology, Institute of Translational Medicine, N. I. Pirogov Russian National Research Medical University, The Ministry of Health of the Russian Federation, Moscow, Russia
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Zheng X, Zhang L, Wu L, Zhao J, Sun J, Fang Y, Zhou J, Chu Q, Shen Y, Yang Z, Chen L, Huang M, Lin X, Liu Z, Shen P, Wang Z, Wang X, Wang H, Han Z, Liu A, Zhang H, Ye F, Gao W, Wu F, Song Z, Chen S, Zhou C, Wang Q, Xu C, Huang D, Zheng X, Miao Q, Jiang K, Xu Y, Wu S, Wang H, Zhang Q, Yang S, Li Y, Chen S, Lin G. Baseline C-reactive protein predicts efficacy of the first-line immune checkpoint inhibitors plus chemotherapy in advanced lung squamous cell carcinoma: a retrospective, multicenter study. BMC Cancer 2023; 23:1244. [PMID: 38104105 PMCID: PMC10725584 DOI: 10.1186/s12885-023-11737-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2023] [Accepted: 12/10/2023] [Indexed: 12/19/2023] Open
Abstract
AIMS To investigate the predictive value of baseline C-reactive protein (CRP) levels on the efficacy of chemotherapy plus immune checkpoint inhibitors (ICI) in patients with advanced lung squamous cell carcinoma (LSCC). MATERIALS AND METHODS In this retrospective multicenter study spanning from January 2016 to December 2020, advanced LSCC patients initially treated with chemotherapy or a combination of chemotherapy and ICI were categorized into normal and elevated CRP subgroups. The relationship between CRP levels and treatment outcomes was analyzed using multivariate Cox proportional hazards models and multivariate logistic regression, focusing primarily on the progression-free survival (PFS) endpoint, and secondarily on overall survival (OS) and objective response rate (ORR) endpoints. Survival curves were generated using the Kaplan-Meier method, with the log-rank test used for comparison between groups. RESULTS Of the 245 patients evaluated, the 105 who received a combination of chemotherapy and ICI with elevated baseline CRP levels exhibited a significant reduction in PFS (median 6.5 months vs. 11.8 months, HR, 1.78; 95% CI: 1.12-2.81; p = 0.013) compared to those with normal CRP levels. Elevated CRP was identified as an independent risk factor for poor PFS through multivariate-adjusted analysis. However, among the 140 patients receiving chemotherapy alone, baseline CRP levels did not significantly influence PFS. Furthermore, within the combination therapy group, there was a notable decrease in the ORR (51% vs. 71%, p = 0.035), coupled with a significantly shorter OS (median 20.9 months vs. 31.5 months, HR, 2.24; 95% CI: 1.13-4.44; p = 0.033). CONCLUSION In patients with advanced LSCC, elevated baseline CRP levels were identified as an independent predictive factor for the efficacy of combination therapy with chemotherapy and ICI, but not in chemotherapy alone. This suggests that CRP may be a valuable biomarker for guiding treatment strategies.
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Affiliation(s)
- Xinlong Zheng
- Department of Thoracic Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, China
| | - Longfeng Zhang
- Department of Thoracic Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, China
| | - Lin Wu
- The Second Department of Thoracic Oncology, the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University/Hunan Cancer Hospital, Changsha, China
| | - Jun Zhao
- Department of Thoracic Medical Oncology, Peking University Cancer Hospital and Institute, Beijing, China
| | - Jianguo Sun
- Cancer Institute, Xinqiao Hospital, Army Medical University, Chongqing, China
| | - Yong Fang
- Department of Medical Oncology, Sir Run Run Shaw Hospital, Zhejiang University, Zhejiang, China
| | - Jin Zhou
- School of Medicine, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, University of Electronic Science and Technology of China, Chengdu, Sichuan, China
| | - Qian Chu
- Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yihong Shen
- Department of Respiratory Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Zhenzhou Yang
- Department of Cancer Center, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Lijin Chen
- Department of Oncology, Affiliated Quanzhou First Hospital of Fujian Medical University, Quanzhou, China
| | - Meijuan Huang
- Department of Thoracic Oncology, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Xiaoyan Lin
- Department of Oncology, Fujian Medical University Union Hospital, Fuzhou, China
| | - Zhenhua Liu
- Department of Medical Oncology, Provincial Clinical College, Fujian Medical University, Fujian provincial hospital, Fuzhou, China
| | - Peng Shen
- Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Zhijie Wang
- Medical Oncology Department, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences, and Peking Union Medical College, Beijing, China
| | - Xin Wang
- Department of Oncology, Zhongshan Hospital of Xiamen University, Xiamen, China
| | - Huijuan Wang
- Department of Respiratory Medicine, the Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China
| | - Zhengbo Han
- Department of Oncology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Anwen Liu
- Department of Oncology, The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Hongmei Zhang
- Department of Oncology, Xijing Hospital, Airforce Military Medical University, Xian, Shanxi, China
| | - Feng Ye
- Department of Medical Oncology, Cancer Hospital, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Teaching Hospital of Fujian Medical University, Xiamen, China
| | - Wen Gao
- Department of Medical Oncology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, Jiangsu, China
| | - Fang Wu
- Department of Oncology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Zhengbo Song
- Department of Clinical Trial, Cancer Hospital of the University of Chinese Academy of Sciences, Hangzhou, Zhejiang, China
| | - Shengchi Chen
- Department of Oncology, Nanping First Hospital Affiliated to Fujian Medical University, Nanping, China
| | - Chenzhi Zhou
- Respiratory Medicine Department, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Qian Wang
- Department of Respiratory Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Chunwei Xu
- Department of Respiratory Medicine, Affiliated Jinling Hospital, Medical School of Nanjing University Nanjing, Nanjing, Jiangsu, China
| | - Dingzhi Huang
- Department of Thoracic Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
| | - Xiaobin Zheng
- Department of Thoracic Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, China
| | - Qian Miao
- Department of Thoracic Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, China
| | - Kan Jiang
- Department of Thoracic Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, China
| | - Yiquan Xu
- Department of Thoracic Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, China
| | - Shiwen Wu
- Department of Thoracic Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, China
| | - Haibo Wang
- Department of Thoracic Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, China
| | - Qiuyu Zhang
- Institute of Immunotherapy, Fujian Medical University, Fuzhou, China
| | - Shanshan Yang
- Department of Thoracic Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, China
| | - Yujing Li
- Department of Thoracic Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, China
| | - Sihui Chen
- Department of Thoracic Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, China
| | - Gen Lin
- Department of Thoracic Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, China.
- Fujian Key Laboratory of Advanced Technology for Cancer Screening and Early Diagnosis, Fuzhou, China.
- Interdisciplinary Institute for Medical Engineering, Fuzhou University, Fuzhou, China.
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8
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Abstract
Glioblastoma (GBM) is among the deadliest malignancies facing modern oncology. While our understanding of certain aspects of GBM biology has significantly increased over the last decade, other aspects, such as the role of bioactive metals in GBM progression, remain understudied. Iron is the most abundant transition metal found within the earth's crust and plays an intricate role in human physiology owing to its ability to participate in oxidation-reduction reactions. The importance of iron homeostasis in human physiology is apparent when examining the clinical consequences of iron deficiency or iron overload. Despite this, the role of iron in GBM progression has not been well described. Here, we review and synthesize the existing literature examining iron's role in GBM progression and patient outcomes, as well as provide a survey of iron's effects on the major cell types found within the GBM microenvironment at the molecular and cellular level. Iron represents an accessible target given the availability of already approved iron supplements and chelators. Improving our understanding of iron's role in GBM biology may pave the way for iron-modulating approaches to improve patient outcomes.
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Affiliation(s)
- Ganesh Shenoy
- Department of Neurosurgery, Penn State College of Medicine, Hershey, PA, USA
| | - James R Connor
- Department of Neurosurgery, Penn State College of Medicine, Hershey, PA, USA
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9
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Serban GM, Tamas CI, Tamas F, Balasa AF. Preoperative Immune-Inflammatory Status of the Patients With Newly-Diagnosed Glioblastoma - Could It Genuinely Predict Their Survival? Cureus 2023; 15:e43802. [PMID: 37731450 PMCID: PMC10508644 DOI: 10.7759/cureus.43802] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/20/2023] [Indexed: 09/22/2023] Open
Abstract
BACKGROUND Glioblastoma multiforme (GBM) is the most aggressive brain tumor affecting adult patients, with an extremely reduced overall survival despite rapid diagnosis and treatment. Therefore, it is crucial to establish accurate and affordable markers that allow an individualized approach to GBM patients. Serum biomarkers could be the most accessible, as complete blood counts should be performed on all GBM patients before undergoing any surgical and/or pharmacological treatment. However, their prognostic role is still unclear. Our study aims to assess the influence of various hematological markers of inflammation in predicting the outcome of GBM patients. MATERIAL AND METHODS We retrospectively analyzed all adult patients diagnosed with primary glioblastoma in the Neurosurgery Department of the Emergency Clinical County Hospital of Târgu Mureș, Romania, from January 2017 until December 2019. We aimed to discover whether the immune/inflammatory status of the patients before receiving any kind of pharmacological or surgical treatment influenced their overall survival. RESULTS Our study showed that pre-therapeutic elevated white blood count could predict reduced overall survival in not otherwise specified subtype (NOS) of GBMs (HR 0.4153, 95% CI 0.1825-0.9449, p 0.0362). Furthermore, patients with increased systemic immune response index (SIRI) had much larger tumors at the time of diagnosis (p 0.0359). In wild type, isocitrate dehydrogenase subpopulation (IDHwt), the higher values of neutrophil-to-lymphocyte ratio (NLR, p 0.0412), platelet-to-lymphocyte ratio (PLR, p 0.0376) and monocyte-to-lymphocyte ratio (MLR, p 0.0412) were related to more advanced age at the moment of diagnosis. Moreover, our results revealed a weakly positive association between tumor size and NLR values in the NOS group (Spearman r 0.3212, p 0.0493). CONCLUSIONS Our study does not provide enough evidence for the immune/inflammatory status of GBM patients to be used as an efficient prognostic marker to guide the therapeutic approach.
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Affiliation(s)
- Georgiana M Serban
- Anesthesiology and Critical Care Clinic, Emergency County Hospital, Targu Mures, ROU
| | - Corina I Tamas
- Neurosurgery Clinic, Emergency County Hospital, Targu Mures, ROU
- Neurosurgery, George Emil Palade University of Medicine, Pharmacy, Science, and Technology, Targu Mures, ROU
| | - Flaviu Tamas
- Neurosurgery, Emergency County Hospital, Targu Mures, ROU
- Neurosurgery, George Emil Palade University of Medicine, Pharmacy, Science, and Technology, Targu Mures, ROU
| | - Adrian F Balasa
- Neurosurgery, Emergency County Hospital, Targu Mures, ROU
- Neurosurgery, George Emil Palade University of Medicine, Pharmacy, Science, and Technology, Targu Mures, ROU
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10
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Jarmuzek P, Kozlowska K, Defort P, Kot M, Zembron-Lacny A. Prognostic Values of Systemic Inflammatory Immunological Markers in Glioblastoma: A Systematic Review and Meta-Analysis. Cancers (Basel) 2023; 15:3339. [PMID: 37444448 DOI: 10.3390/cancers15133339] [Citation(s) in RCA: 38] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2023] [Revised: 06/13/2023] [Accepted: 06/19/2023] [Indexed: 07/15/2023] Open
Abstract
BACKGROUND Neutrophils are an important part of the tumor microenvironment, which stimulates inflammatory processes through phagocytosis, degranulation, release of small DNA fragments (cell-free DNA), and presentation of antigens. Since neutrophils accumulate in peripheral blood in patients with advanced-stage cancer, a high neutrophil-to-lymphocyte ratio can be a biomarker of a poor prognosis in patients with glioblastoma. The present study aimed to explore the prognostic value of the preoperative levels of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune inflammation index (SII), systemic inflammation response index (SIRI), and cell-free DNA (cfDNA) to better predict prognostic implications in the survival rate of glioblastoma patients. METHODS The meta-analysis was carried out according to the recommendations and standards established by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Databases of PubMed, EBSCO, and Medline were systematically searched to select all the relevant studies published up to December 2022. RESULTS Poorer prognoses were recorded in patients with a high NLR or PLR when compared with the patients with a low NLR or PLR (HR 1.51, 95% CI 1.24-1.83, p < 0.0001 and HR 1.34, 95% CI 1.10-1.63, p < 0.01, respectively). Similarly, a worse prognosis was reported for patients with a higher cfDNA (HR 2.35, 95% CI 1.27-4.36, p < 0.01). The SII and SIRI values were not related to glioblastoma survival (p = 0.0533 and p = 0.482, respectively). CONCLUSIONS Thus, NLR, PLR, and cfDNA, unlike SII and SIRI, appeared to be useful and convenient peripheral inflammatory markers to assess the prognosis in glioblastoma.
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Affiliation(s)
- Pawel Jarmuzek
- Department of Nervous System Diseases, Collegium Medicum University of Zielona Gora, Neurosurgery Center University Hospital in Zielona Gora, 65-417 Zielona Gora, Poland
| | - Klaudia Kozlowska
- Department of Biomedical Engineering, Faculty of Fundamental Problems of Technology, Wroclaw University of Science and Technology, 50-370 Wroclaw, Poland
| | - Piotr Defort
- Department of Nervous System Diseases, Collegium Medicum University of Zielona Gora, Neurosurgery Center University Hospital in Zielona Gora, 65-417 Zielona Gora, Poland
| | - Marcin Kot
- Department of Nervous System Diseases, Collegium Medicum University of Zielona Gora, Neurosurgery Center University Hospital in Zielona Gora, 65-417 Zielona Gora, Poland
| | - Agnieszka Zembron-Lacny
- Department of Applied and Clinical Physiology, Collegium Medicum University of Zielona Gora, 65-417 Zielona Gora, Poland
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11
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Choi YK, Jang HS, Choi BO, Lee SW, Song JH. Impact of radiation on immune cells in patients with low-grade brain tumor: Identifying critical factors affecting lymphopenia and neutrophil-to-lymphocyte ratio. Radiat Oncol J 2023; 41:120-128. [PMID: 37403354 DOI: 10.3857/roj.2022.00668] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2022] [Accepted: 05/26/2023] [Indexed: 07/06/2023] Open
Abstract
PURPOSE Studies about the effect of radiation therapy (RT) on immune cells are usually limited to a high-grade glioma mostly exposed to chemotherapy and a high dose of steroid which also could affect immune cells. The purpose of this retrospective analysis of low-grade brain tumor patients treated by RT alone is to determine significant factors influencing neutrophil-to-lymphocyte ratio (NLR), absolute neutrophil counts (ANC), and absolute lymphocyte counts (ALC). MATERIALS AND METHODS A total of 41 patients who received RT between 2007 and 2020 were analyzed. Patients who received chemotherapy and high-dose of steroid were excluded. ANC and ALC were collected before starting RT (baseline) and within one-week before ending RT (post-treatment). Changes of ANC, ALC, and NLR between baseline and post-treatment were calculated. RESULTS ALC decreased in 32 patients (78.1%). NLR increased in 31 patients (75.6%). No patients developed grade 2 or higher hematologic toxicities. The decrease of ALC was significantly correlated with the dose to brain V15 in a simple and multiple linear regression (p = 0.043). Brain V10 and V20 adjacent to V15 were also marginally significant factors determining the reduction of lymphocytes (p = 0.050 and p = 0.059, respectively). However, it was difficult to find predictive factors affecting changes of ANC and NLR. CONCLUSION In low-grade brain tumor patients who are treated by RT alone, ALC decreased and NLR increased in three-fourth of patients, although the magnitude was minimal. The decrease of ALC was mainly affected by low dose to the brain. However, RT dose was not correlated with changes of ANC or NLR.
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Affiliation(s)
- Yoo Kyung Choi
- Department of Radiation Oncology, Seoul St. Mary's Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Hong Seok Jang
- Department of Radiation Oncology, Seoul St. Mary's Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Byung Ok Choi
- Department of Radiation Oncology, Seoul St. Mary's Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Sea-Won Lee
- Department of Radiation Oncology, Eunpyeong St. Mary's Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Jin Ho Song
- Department of Radiation Oncology, Seoul St. Mary's Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea
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12
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Guidry BS, Chotai S, Tang AR, Le CH, Grisham CJ, McDermott JR, Kelly PD, Morone PJ, Thompson RC, Chambless LB. Association between preoperative hematologic markers and aggressive behavior in meningiomas. Clin Neurol Neurosurg 2023; 226:107629. [PMID: 36822137 DOI: 10.1016/j.clineuro.2023.107629] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Revised: 01/03/2023] [Accepted: 02/12/2023] [Indexed: 02/18/2023]
Abstract
INTRODUCTION Meningiomas have varying degrees of aggressive behavior. Some systemic hematologic makers are associated with malignancy, but their value in predicting aggressive meningioma behavior is not fully understood. OBJECTIVE To evaluate the association between preoperative markers such as neutrophil-lymphocyte ratio (NLR), neutrophil-monocyte ratio (NMR), monocyte-lymphocyte ratio (MLR), platelet-lymphocyte ratio (PLR), and prognostic nutritional index (PNI), and diagnostic and prognostic factors including WHO grade, proliferation index, presence of edema on preoperative MRI, and tumor recurrence. METHODS A retrospective review of patients treated between 2000 and 2019 with a preoperative complete blood count (CBC) differential lab draw before intracranial meningioma resection was conducted. All preoperative steroid dosages were converted to dexamethasone equivalents. Primary outcomes included presence/absence of perilesional edema, WHO grade, Ki-67/MIB-index, and recurrence. Univariate and multivariable regression analyses were conducted. RESULTS A total of 209 meningioma patients were included. Of these, 143 (68 %) were WHO grade I, 61 (29 %) grade II and 5 (2 %) were grade III. Recurrence was reported in 19 (9.1 %) tumors. No hematologic markers were associated with recurrence. In separate multivariable logistic analyses, no biomarkers were associated with perilesional edema or WHO grade. MLR was associated with higher MIB-index (p = 0.018, OR 6.57, 95 % CI 1.37-30.91). CONCLUSION Most hematologic markers were not associated with meningioma invasiveness, grade, proliferative index, or aggressiveness. Preoperative MLR was associated with high proliferation index in patients undergoing surgery for intracranial meningioma. Higher MLR could be a surrogate for meningioma proliferation and has potential to be used as an adjunct for risk-stratifying meningiomas.
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Affiliation(s)
| | - Silky Chotai
- Department of Neurological Surgery, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Alan R Tang
- Vanderbilt University School of Medicine, Nashville, TN, USA
| | - Chi H Le
- Vanderbilt University School of Medicine, Nashville, TN, USA
| | | | | | - Patrick D Kelly
- Department of Neurological Surgery, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Peter J Morone
- Department of Neurological Surgery, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Reid C Thompson
- Department of Neurological Surgery, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Lola B Chambless
- Department of Neurological Surgery, Vanderbilt University Medical Center, Nashville, TN, USA.
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13
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Huang B, Zhang J, Zong W, Chen S, Zong Z, Zeng X, Zhang H. Myeloidcells in the immunosuppressive microenvironment in glioblastoma: The characteristics and therapeutic strategies. Front Immunol 2023; 14:994698. [PMID: 36923402 PMCID: PMC10008967 DOI: 10.3389/fimmu.2023.994698] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2022] [Accepted: 01/31/2023] [Indexed: 03/03/2023] Open
Abstract
Glioblastoma (GBM) is the most common and lethal malignant tumor of the central nervous system in adults. Conventional therapies, including surgery, radiotherapy, and chemotherapy, have limited success in ameliorating patient survival. The immunosuppressive tumor microenvironment, which is infiltrated by a variety of myeloid cells, has been considered a crucial obstacle to current treatment. Recently, immunotherapy, which has achieved great success in hematological malignancies and some solid cancers, has garnered extensive attention for the treatment of GBM. In this review, we will present evidence on the features and functions of different populations of myeloid cells, and on current clinical advances in immunotherapies for glioblastoma.
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Affiliation(s)
- Boyuan Huang
- Department of Neurosurgery, Capital Medical University Electric Power Teaching Hospital/State Grid Beijing Electric Power Hospital, Beijing, China
| | - Jin Zhang
- Department of Neurosurgery, The First Affiliated Hospital, Jinan University, Guangzhou, China
| | - Wenjing Zong
- Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China
| | - Sisi Chen
- Department of neurosurgery, Jiujiang Hospital of Traditional Chinese Medicine, Jiujiang, China
| | - Zhitao Zong
- Department of neurosurgery, Jiujiang Hospital of Traditional Chinese Medicine, Jiujiang, China
| | - Xiaojun Zeng
- Department of Neurosurgery, Shenzhen Key Laboratory of Neurosurgery, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, China
| | - Hongbo Zhang
- Department of Neurosurgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China
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14
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Yamada E, Ishikawa E, Miyazaki T, Miki S, Sugii N, Kohzuki H, Tsurubuchi T, Sakamoto N, Watanabe S, Matsuda M. P53-negative status and gross total resection as predictive factors for autologous tumor vaccine treatment in newly diagnosed glioblastoma patients. Neurooncol Adv 2023; 5:vdad079. [PMID: 37484760 PMCID: PMC10362834 DOI: 10.1093/noajnl/vdad079] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/25/2023] Open
Abstract
Background Among primary brain tumors, glioblastoma (GBM) is the most common and aggressive in adults, with limited treatment options. Our previous study showed that autologous formalin-fixed tumor vaccine (AFTV) contributed to prognostic improvements in newly diagnosed GBM patients. However, some patients died early despite the treatment. The discovery of predictive factors in the treatment was warranted for efficient patient recruitment and studies to overcome resistance mechanisms. Identifying prognostic factors will establish AFTV guidelines for patients who may respond to the therapy. Methods Data from 58 patients with newly diagnosed GBM, including 29 who received standard therapy plus AFTV (AFTV group) and 29 who received standard treatment (control group) were analyzed. Several data including patient age, sex, the extent of removal, and various cell immunohistochemistry (IHC) parameters were also included in the analysis. Results Both univariate and multivariate analyses revealed that gross total resection (GTR) and negative p53 were associated with a better prognosis only in the AFTV group. In the IHC parameters, CD8 staining status was also one of the predictive factors in the univariate analysis. For blood cell-related data, lymphocyte counts of 1100 or more and monocyte counts of 280 or more before chemo-radiotherapy were significant factors for good prognosis in the univariate analysis. Conclusions A p53-negative status in IHC and GTR were the predictive factors for AFTV treatment in newly diagnosed GBM patients. Microenvironment-targeted treatment and pretreatment blood cell status may be key factors to enhance therapy effects.
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Affiliation(s)
| | - Eiichi Ishikawa
- Corresponding Author: Eiichi Ishikawa, MD, PhD, Department of Neurosurgery, Institute of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan ()
| | | | - Shunichiro Miki
- Department of Neurosurgery, Institute of Medicine, University of Tsukuba, Ibaraki, Japan
| | - Narushi Sugii
- Department of Neurosurgery, Institute of Medicine, University of Tsukuba, Ibaraki, Japan
| | - Hidehiro Kohzuki
- Department of Neurosurgery, Institute of Medicine, University of Tsukuba, Ibaraki, Japan
| | - Takao Tsurubuchi
- Department of Neurosurgery, Institute of Medicine, University of Tsukuba, Ibaraki, Japan
| | - Noriaki Sakamoto
- Diagnostic Pathology, Institute of Medicine, University of Tsukuba, Ibaraki, Japan
| | - Shinya Watanabe
- Department of Neurosurgery, Institute of Medicine, University of Tsukuba, Ibaraki, Japan
| | - Masahide Matsuda
- Department of Neurosurgery, Institute of Medicine, University of Tsukuba, Ibaraki, Japan
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15
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Safcak D, Drazilova S, Gazda J, Andrasina I, Adamcova-Selcanova S, Balazova L, Barila R, Mego M, Rac M, Skladany L, Zigrai M, Janicko M, Jarcuska P. Inflammatory Indexes as Prognostic Factors of Survival in Geriatric Patients with Hepatocellular Carcinoma: A Case Control Study of Eight Slovak Centers. J Clin Med 2022; 11:4183. [PMID: 35887947 PMCID: PMC9318669 DOI: 10.3390/jcm11144183] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2022] [Revised: 07/08/2022] [Accepted: 07/14/2022] [Indexed: 02/04/2023] Open
Abstract
Background and Aims: Hepatocellular cancer (HCC) often occurs in geriatric patients. The aim of our study was to compare overall survival and progression-free survival between geriatric patients (>75 years) and patients younger than 75 years and to identify predictive factors of survival in geriatric patients with HCC. Material and Methods: We performed a retrospective analysis of patients with HCC diagnosed in Slovakia between 2010−2016. Cases (HCC patients ≥75 years) were matched to controls (HCC patients <74 years) based on the propensity score (gender, BCLC stage and the first-line treatment). Results: We included 148 patients (84 men, 57%) with HCC. There were no differences between cases and controls in the baseline characteristics. The overall survival in geriatric patients with HCC was comparable to younger controls (p = 0.42). The one-, two-, and three-year overall survival was 42% and 31%, 19% and 12%, and 12% and 9% in geriatric patients and controls, respectively (p = 0.2, 0.4, 0.8). Similarly, there was no difference in the one- and two-year progression-free survival: 28% and 18% vs. 10% and 7% in geriatric HCC patients and controls, respectively (p = 0.2, 1, -). There was no case−control difference between geriatric HCC patients and younger HCC controls in the overall survival in the subpopulation of patients with no known comorbidities (p = 0.5), one and two comorbidities (p = 0.49), and three or more comorbidities (p = 0.39). Log (CRP), log (NLR), log (PLR), and log (SII) were all associated with the three-year survival in geriatric HCC patients in simple logistic regression analyses. However, this time, only log (NLR) remained associated even after controlling for the age and BCLC confounding (OR 5.32, 95% CI 1.43−28.85). Conclusions. We found no differences in overall survival and progression-free survival between older and younger HCC patients. Parameters of subclinical inflammation predict prognosis in geriatric patients with HCC. A limitation of the study is small number of the treated patients; therefore, further investigation is warranted.
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Affiliation(s)
- Dominik Safcak
- Department of Radiotherapy and Oncology, East Slovakia Institute of Oncology, Rastislavova 43, 041 91 Kosice, Slovakia; (D.S.); (I.A.); (L.B.)
| | - Sylvia Drazilova
- Internal Medicine Department, Hospital Poprad a.s., Banicka 803, 058 01 Poprad, Slovakia
- 2nd Department of Internal Medicine, P. J. Safarik University, Faculty of Medicine and L. Pasteur University Hospital, Trieda SNP 1, 040 11 Kosice, Slovakia; (J.G.); (M.J.); (P.J.)
| | - Jakub Gazda
- 2nd Department of Internal Medicine, P. J. Safarik University, Faculty of Medicine and L. Pasteur University Hospital, Trieda SNP 1, 040 11 Kosice, Slovakia; (J.G.); (M.J.); (P.J.)
| | - Igor Andrasina
- Department of Radiotherapy and Oncology, East Slovakia Institute of Oncology, Rastislavova 43, 041 91 Kosice, Slovakia; (D.S.); (I.A.); (L.B.)
| | - Svetlana Adamcova-Selcanova
- 2nd Department of Internal Medicine, HEGITO, F. D. Roosevelt University Hospital, Namestie L Svobodu 1, 975 17 Banska Bystrica, Slovakia; (S.A.-S.); (L.S.)
| | - Lea Balazova
- Department of Radiotherapy and Oncology, East Slovakia Institute of Oncology, Rastislavova 43, 041 91 Kosice, Slovakia; (D.S.); (I.A.); (L.B.)
| | - Radovan Barila
- Oncological Cluster, Stefan Kukura Hospital in Michalovce, Spitalska Ulica 2, 071 01 Michalovce, Slovakia;
| | - Michal Mego
- 2nd Department of Oncology, Faculty of Medicine, Comenius University and National Oncology Institute of Slovakia, Klenova 1, 833 10 Bratislava, Slovakia;
| | - Marek Rac
- Department of Internal Medicine, Teaching Hospital Nitra, Spitalska 6, 949 01 Nitra, Slovakia;
| | - Lubomir Skladany
- 2nd Department of Internal Medicine, HEGITO, F. D. Roosevelt University Hospital, Namestie L Svobodu 1, 975 17 Banska Bystrica, Slovakia; (S.A.-S.); (L.S.)
| | - Miroslav Zigrai
- 1st Department of Internal Medicine, Ladislav Derer University Hospital in Bratislava, Limbova 5, 833 05 Bratislava-Kramare, Slovakia;
| | - Martin Janicko
- 2nd Department of Internal Medicine, P. J. Safarik University, Faculty of Medicine and L. Pasteur University Hospital, Trieda SNP 1, 040 11 Kosice, Slovakia; (J.G.); (M.J.); (P.J.)
| | - Peter Jarcuska
- 2nd Department of Internal Medicine, P. J. Safarik University, Faculty of Medicine and L. Pasteur University Hospital, Trieda SNP 1, 040 11 Kosice, Slovakia; (J.G.); (M.J.); (P.J.)
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16
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Jarmuzek P, Kot M, Defort P, Stawicki J, Komorzycka J, Nowak K, Tylutka A, Zembron-Lacny A. Prognostic Values of Combined Ratios of White Blood Cells in Glioblastoma: A Retrospective Study. J Clin Med 2022; 11:3397. [PMID: 35743468 PMCID: PMC9225636 DOI: 10.3390/jcm11123397] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2022] [Revised: 06/02/2022] [Accepted: 06/07/2022] [Indexed: 12/20/2022] Open
Abstract
In some malignant tumours, the changes in neutrophil counts in relation to other blood cells are connected with unfavourable prognosis. Nevertheless, the prognostic value of the combinations of the haematological components in glioblastoma (GBM) remains under dispute. The clinical significance of the neutrophil-to-lymphocyte ratio (NLR), systemic immune inflammation index (SII), and systemic inflammation response index (SIRI) was investigated in our study. We retrospectively studied 358 patients (males n = 195; females n = 163) aged 59.9 ± 13.5 yrs with newly diagnosed glioma and admitted to the Neurosurgery Centre. Routine blood tests and clinical characteristics were recorded within the first hour of hospital admission. The inflammatory variables: NLR, SII and SIRI exceeded the reference values and were significantly elevated in Grade 3 and Grade 4 tumour. The Cox model analysis showed that the age ≥ 63 years, NLR ≥ 4.56 × 103/µL, SII ≥ 2003 × 103/µL and SIRI ≥ 3.03 × 103/µL significantly increased the risk of death in Grade 4 tumour patients. In the inflammatory variables, NLR demonstrated the highest impact on the survival time (HR 1.56; 95% CI 1.145-2.127; p = 0.005). In the first Polish study including GBM patients, the age in relation to simple parameters derived from complete blood cell count were found to have prognostic implications in the survival rate.
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Affiliation(s)
- Pawel Jarmuzek
- Neurosurgery Center University Hospital, Collegium Medicum University of Zielona Gora, 28 Zyty Str., 65-417 Zielona Gora, Poland; (P.J.); (M.K.); (J.S.)
| | - Marcin Kot
- Neurosurgery Center University Hospital, Collegium Medicum University of Zielona Gora, 28 Zyty Str., 65-417 Zielona Gora, Poland; (P.J.); (M.K.); (J.S.)
| | - Piotr Defort
- Neurosurgery Center University Hospital, Collegium Medicum University of Zielona Gora, 28 Zyty Str., 65-417 Zielona Gora, Poland; (P.J.); (M.K.); (J.S.)
| | - Jakub Stawicki
- Neurosurgery Center University Hospital, Collegium Medicum University of Zielona Gora, 28 Zyty Str., 65-417 Zielona Gora, Poland; (P.J.); (M.K.); (J.S.)
| | - Julia Komorzycka
- Student Research Group, Collegium Medicum University of Zielona Gora, 28 Zyty Str., 65-417 Zielona Gora, Poland; (J.K.); (K.N.)
| | - Karol Nowak
- Student Research Group, Collegium Medicum University of Zielona Gora, 28 Zyty Str., 65-417 Zielona Gora, Poland; (J.K.); (K.N.)
| | - Anna Tylutka
- Department of Applied and Clinical Physiology, Collegium Medicum University of Zielona Gora, 28 Zyty Str., 65-417 Zielona Gora, Poland; (A.T.); (A.Z.-L.)
| | - Agnieszka Zembron-Lacny
- Department of Applied and Clinical Physiology, Collegium Medicum University of Zielona Gora, 28 Zyty Str., 65-417 Zielona Gora, Poland; (A.T.); (A.Z.-L.)
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Goutnik M, Lucke-Wold B. Commentary: Evaluating potential glioma serum biomarkers, with future applications. World J Clin Oncol 2022; 13:412-416. [PMID: 35662986 PMCID: PMC9153077 DOI: 10.5306/wjco.v13.i5.412] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2021] [Revised: 03/15/2022] [Accepted: 05/14/2022] [Indexed: 02/06/2023] Open
Abstract
Systemic inflammation within malignant glioma is a topic of ongoing significance. In this commentary, we highlight recent findings from Gandhi et al and discuss alternative approaches. We present a counter argument with findings that IL-6 markers are controversial. We highlight the potential benefit of looking at microRNAs and other biomarkers. Finally, we present ideas for future application involving differentiation between radiation necrosis and recurrence. The commentary is intended to serve as a catalyst for further scientific discovery.
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Affiliation(s)
- Michael Goutnik
- Department of Neurosurgery, University of Florida, Gainesville, FL 32608, United States
| | - Brandon Lucke-Wold
- Department of Neurosurgery, University of Florida, Gainesville, FL 32608, United States
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18
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Filippova N, Grimes JM, Leavenworth JW, Namkoong D, Yang X, King PH, Crowley M, Crossman DK, Nabors LB. Targeting the TREM1-positive myeloid microenvironment in glioblastoma. Neurooncol Adv 2022; 4:vdac149. [PMID: 36249290 PMCID: PMC9555298 DOI: 10.1093/noajnl/vdac149] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023] Open
Abstract
Background Tumor cellular and molecular heterogeneity is a hallmark of glioblastoma and underlies treatment resistance and recurrence. This manuscript investigated the myeloid-derived microenvironment as a driver of glioblastoma heterogeneity and provided a pharmacological pathway for its suppression. Methods Transcriptomic signatures of glioblastoma infiltrated myeloid-derived cells were assessed using R2: genomic platform, Ivy Glioblastoma Spatial Atlas, and single-cell RNA-seq data of primary and recurrent glioblastomas. Myeloid-derived cell prints were evaluated in five PDX cell lines using RNA-seq data. Two immunocompetent mouse glioblastoma models were utilized to isolate and characterize tumor-infiltrated myeloid-derived cells and glioblastoma/host cell hybrids. The ability of an inhibitor of HuR dimerization SRI42127 to suppress TREM1+-microenvironment and glioblastoma/myeloid-derived cell interaction was assessed in vivo and in vitro. Results TREM1+-microenvironment is enriched in glioblastoma peri-necrotic zones. TREM1 appearance is enhanced with tumor grade and associated with poor patient outcomes. We confirmed an expression of a variety of myeloid-derived cell markers, including TREM1, in PDX cell lines. In mouse glioblastoma models, we demonstrated a reduction in the TREM1+-microenvironment and glioblastoma/host cell fusion after treatment with SRI42127. In vitro assays confirmed inhibition of cell fusion events and reduction of myeloid-derived cell migration towards glioblastoma cells by SRI42127 and TREM1 decoy peptide (LP17) versus control treatments. Conclusions TREM1+-myeloid-derived microenvironment promulgates glioblastoma heterogeneity and is a therapeutic target. Pharmacological inhibition of HuR dimerization leads to suppression of the TREM1+-myeloid-derived microenvironment and the neoplastic/non-neoplastic fusogenic cell network.
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Affiliation(s)
- Natalia Filippova
- Department of Neurology, Division of Neuro-oncology, UAB, Birmingham, Alabama, USA
| | - Jeffrey M Grimes
- Department of Neurosurgery, Program of Immunology, UAB, Birmingham, Alabama, USA
| | | | - David Namkoong
- Department of Neurology, Division of Neuro-oncology, UAB, Birmingham, Alabama, USA
| | - Xiuhua Yang
- Department of Neurology, Division of Neuro-oncology, UAB, Birmingham, Alabama, USA
| | - Peter H King
- Department of Neurology, Birmingham Veterans Affairs Medical Center, Birmingham, Alabama, USA
| | - Michael Crowley
- Department of Genetics, Heflin Center Genomics Core, UAB, Birmingham, Alabama, USA (M.C., D.K.C.)
| | - David K Crossman
- Department of Genetics, Heflin Center Genomics Core, UAB, Birmingham, Alabama, USA (M.C., D.K.C.)
| | - L Burt Nabors
- Department of Neurology, Division of Neuro-oncology, UAB, Birmingham, Alabama, USA
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19
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Yan P, Li JW, Mo LG, Huang QR. A nomogram combining inflammatory markers and clinical factors predicts survival in patients with diffuse glioma. Medicine (Baltimore) 2021; 100:e27972. [PMID: 34964788 PMCID: PMC8615312 DOI: 10.1097/md.0000000000027972] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2021] [Accepted: 11/10/2021] [Indexed: 01/05/2023] Open
Abstract
In this study, we aimed to investigate the prognostic value of neutrophil/lymphocyte ratio (NLR), monocyte/lymphocyte ratio (MLR), and platelet/lymphocyte ratio (PLR) in diffuse glioma, and to establish a prognostic nomogram accordingly.The hematologic and clinicopathological data of 162 patients with primary diffuse glioma who received surgical treatment from January 2012 to December 2018 were retrospectively analyzed. Receiver operator characteristic (ROC) curve was carried out to determine the optimal cut-off values for NLR, MLR, PLR, age, and Ki-67 index, respectively. Kaplan-Meier method was used to investigate the correlation between inflammatory indicators and prognosis of glioma patients. Univariate and multivariate Cox regression were performed to evaluate the independent prognostic value of each parameter in glioma. Then, a nomogram was developed to predict 1-, 3-, and 5-year postoperative survival in diffuse glioma patients based on independent prognostic factors. Subsequent time-dependent ROC curve, calibration curve, decision curve analysis (DCA), and concordance index (C-index) were performed to assess the predictive performance of the nomogram.The Kaplan-Meier curve indicated that patients with high levels of NLR, MLR, and PLR had a poor prognosis. In addition, we found that NLR level was associated with World Health Organization (WHO) grade and IDH status of glioma. The multivariate Cox analysis indicated that resection extent, WHO grade, and NLR level were independent prognostic factors, and we established a nomogram that included these three parameters. The evaluation of the nomogram indicated that the nomogram had a good predictive performance, and the addition of NLR could improve the accuracy.NLR, MLR, and PLR were prognostic factors of diffuse glioma. In addition, the nomogram including NLR was reliable for predicting survival of diffuse glioma patients.
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20
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Alghamri MS, McClellan BL, Avvari RP, Thalla R, Carney S, Hartlage CS, Haase S, Ventosa M, Taher A, Kamran N, Zhang L, Faisal SM, Núñez FJ, Garcia-Fabiani MB, Al-Holou WN, Orringer D, Hervey-Jumper S, Heth J, Patil PG, Eddy K, Merajver SD, Ulintz PJ, Welch J, Gao C, Liu J, Núñez G, Hambardzumyan D, Lowenstein PR, Castro MG. G-CSF secreted by mutant IDH1 glioma stem cells abolishes myeloid cell immunosuppression and enhances the efficacy of immunotherapy. SCIENCE ADVANCES 2021; 7:eabh3243. [PMID: 34586841 PMCID: PMC8480930 DOI: 10.1126/sciadv.abh3243] [Citation(s) in RCA: 62] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Accepted: 08/06/2021] [Indexed: 05/24/2023]
Abstract
Mutant isocitrate-dehydrogenase 1 (mIDH1) synthesizes the oncometabolite 2-hydroxyglutarate (2HG), which elicits epigenetic reprogramming of the glioma cells’ transcriptome by inhibiting DNA and histone demethylases. We show that the efficacy of immune-stimulatory gene therapy (TK/Flt3L) is enhanced in mIDH1 gliomas, due to the reprogramming of the myeloid cells’ compartment infiltrating the tumor microenvironment (TME). We uncovered that the immature myeloid cells infiltrating the mIDH1 TME are mainly nonsuppressive neutrophils and preneutrophils. Myeloid cell reprogramming was triggered by granulocyte colony-stimulating factor (G-CSF) secreted by mIDH1 glioma stem/progenitor-like cells. Blocking G-CSF in mIDH1 glioma–bearing mice restores the inhibitory potential of the tumor-infiltrating myeloid cells, accelerating tumor progression. We demonstrate that G-CSF reprograms bone marrow granulopoiesis, resulting in noninhibitory myeloid cells within mIDH1 glioma TME and enhancing the efficacy of immune-stimulatory gene therapy.
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Affiliation(s)
- Mahmoud S. Alghamri
- Department of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA
- Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
| | - Brandon L. McClellan
- Department of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA
- Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
- Graduate Program in Immunology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
| | - Ruthvik P. Avvari
- Department of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA
- Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
| | - Rohit Thalla
- Department of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA
- Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
| | - Stephen Carney
- Department of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA
- Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
| | - Carson S. Hartlage
- Department of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA
- Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
| | - Santiago Haase
- Department of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA
- Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
| | - Maria Ventosa
- Department of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA
- Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
| | - Ayman Taher
- Department of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA
- Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
| | - Neha Kamran
- Department of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA
- Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
| | - Li Zhang
- Department of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA
- Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
| | - Syed Mohd Faisal
- Department of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA
- Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
| | - Felipe J. Núñez
- Department of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA
- Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
| | - María Belén Garcia-Fabiani
- Department of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA
- Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
| | - Wajd N. Al-Holou
- Department of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA
| | - Daniel Orringer
- Department of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA
| | - Shawn Hervey-Jumper
- Department of Neurosurgery, University of California San Francisco, San Francisco, CA 94143, USA
| | - Jason Heth
- Department of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA
| | - Parag G. Patil
- Department of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA
| | - Karen Eddy
- Department of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA
| | - Sofia D. Merajver
- Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA
| | - Peter J. Ulintz
- Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA
| | - Joshua Welch
- Department of Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, MI 48109, USA
| | - Chao Gao
- Department of Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, MI 48109, USA
| | - Jialin Liu
- Department of Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, MI 48109, USA
| | - Gabriel Núñez
- Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
| | - Dolores Hambardzumyan
- Department of Oncological Sciences, The Tisch Cancer Institute, and Department of Neurosurgery, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
| | - Pedro R. Lowenstein
- Department of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA
- Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
- Rogel Cancer Center, University of Michigan, Ann Arbor, MI 48109, USA
| | - Maria G. Castro
- Department of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA
- Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
- Rogel Cancer Center, University of Michigan, Ann Arbor, MI 48109, USA
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21
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Koudriavtseva T, Villani V, Lorenzano S, Giannarelli D, Di Domenico EG, Stefanile A, Maschio M, D'Agosto G, Pimpinelli F, Tanzilli A, Galiè E, Pace A. Neutrophil-to-lymphocyte ratio, Factor VIII and Antithrombin III: inflammatory-clotting biomarkers in glioma. EXCLI JOURNAL 2021; 20:1152-1169. [PMID: 34345234 PMCID: PMC8326499 DOI: 10.17179/excli2021-3831] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Accepted: 07/02/2021] [Indexed: 11/10/2022]
Abstract
One of the key difficulties in glioma treatment is our limited ability to consistently assess cancer response or progression either by neuroimaging or specific blood biomarkers. An ideal biomarker could be measured through non-invasive methods such as blood-based biomarkers, aiding both early diagnosis and monitoring disease evolution. This is a single-center, case-control, 10-year retrospective, longitudinal study. We evaluated routine coagulation factors in 138 glioma patients (45 Females/93 Males; median [range] age, 56.4 [27-82] years; 64 non-recurrent/74 recurrent) and, for comparison, in 56 relapsing-remitting MS patients (41 Females/15 Males; 40.8 [25-62] years, 35 stable/21 active) and 23 controls (16 Females/7 Males; 41.7 [24-62] years) as well as Neutrophil-to-lymphocyte ratio (NLR) in subgroups of 127 glioma patients, 33 MS patients and 23 healthy controls. Secondly, we assessed whether these indicators could be predictive of overall (OS) and progression-free survival (PFS) in glioma patients. NLR, d-dimer, Antithrombin III and Factor VIII were significantly higher in glioma patients compared to both MS patients and controls (p<0.0001 for all). ROC curves confirmed that either NLR, Antithrombin III or Factor VIII were moderately accurate biomarkers (0.7<AUC<0.9) for glioma patients compared to other two groups whereas d-dimer was a moderately accurate marker for glioma only when compared to controls. In multivariable analysis, NLR ≥ 4.3 (median) (HR 1.53 [95 % CI 1.04-2.26], p=0.03) together with the Karnofsky Performance Status (KPS) ≥ 80 (median) (0.46 [0.31-0.69], p<0.0001) and use of steroids (1.75 [1.19-2.57], p=0.004) resulted independent predictors of OS while only KPS was independently associated with PFS. Our study showed increased levels of either NLR, Antithrombin III, Factor VIII, or d-dimer in glioma patients compared to MS patients and controls, where the first three represented moderately accurate biomarkers for this cancer. Among these markers, only NLR was found to be predictive for OS along with severe disability and steroid therapy.
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Affiliation(s)
- Tatiana Koudriavtseva
- Department of Clinical Experimental Oncology, IRCCS Regina Elena National Cancer Institute, IFO, Via Elio Chianesi 53, 00144, Rome, Italy
| | - Veronica Villani
- Department of Clinical Experimental Oncology, IRCCS Regina Elena National Cancer Institute, IFO, Via Elio Chianesi 53, 00144, Rome, Italy
| | - Svetlana Lorenzano
- Department of Human Neurosciences, Sapienza University of Rome, Rome, Italy
| | - Diana Giannarelli
- Biostatistics, IRCCS Regina Elena National Cancer Institute, IFO, Rome, Italy
| | - Enea Gino Di Domenico
- Clinical Pathology and Microbiology Unit, IRCCS San Gallicano Institute, IFO, Rome, Italy
| | - Annunziata Stefanile
- Department of Clinical Experimental Oncology, IRCCS Regina Elena National Cancer Institute, IFO, Via Elio Chianesi 53, 00144, Rome, Italy
| | - Marta Maschio
- Department of Clinical Experimental Oncology, IRCCS Regina Elena National Cancer Institute, IFO, Via Elio Chianesi 53, 00144, Rome, Italy
| | - Giovanna D'Agosto
- Clinical Pathology and Microbiology Unit, IRCCS San Gallicano Institute, IFO, Rome, Italy
| | - Fulvia Pimpinelli
- Clinical Pathology and Microbiology Unit, IRCCS San Gallicano Institute, IFO, Rome, Italy
| | - Antonio Tanzilli
- Department of Clinical Experimental Oncology, IRCCS Regina Elena National Cancer Institute, IFO, Via Elio Chianesi 53, 00144, Rome, Italy
| | - Edvina Galiè
- Department of Clinical Experimental Oncology, IRCCS Regina Elena National Cancer Institute, IFO, Via Elio Chianesi 53, 00144, Rome, Italy
| | - Andrea Pace
- Department of Clinical Experimental Oncology, IRCCS Regina Elena National Cancer Institute, IFO, Via Elio Chianesi 53, 00144, Rome, Italy
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22
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Garrett C, Becker TM, Lynch D, Po J, Xuan W, Scott KF, de Souza P. Comparison of neutrophil to lymphocyte ratio and prognostic nutritional index with other clinical and molecular biomarkers for prediction of glioblastoma multiforme outcome. PLoS One 2021; 16:e0252614. [PMID: 34138894 PMCID: PMC8211244 DOI: 10.1371/journal.pone.0252614] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2021] [Accepted: 05/19/2021] [Indexed: 11/18/2022] Open
Abstract
Objective Pre- and post-operative neutrophil to lymphocyte ratio (NLR) and prognostic nutritional index (PNI) and other prognostic clinicopathological variables were correlated with progression free survival (PFS) and overall survival (OS) of Glioblastoma Multiforme (GBM) patients. Methods GBM patients (n = 87, single-centre, recruited 2013–2019) were retrospectively divided into low and high groups using literature-derived cut-offs (NLR = 5.07, PNI = 46.97). Kaplan-Meier survival curves and log rank tests assessed PFS and OS. Univariate and multivariate analyses identified PFS and OS prognosticators. Results High vs low post-operative PNI cohort was associated with longer PFS (279 vs 136 days, p = 0.009), but significance was lost on multivariate analysis. Post-operative ECOG (p = 0.043), daily dexamethasone (p = 0.023) and IDH mutation (p = 0.046) were significant on multivariate analysis for PFS. High pre- and post-operative PNI were associated with improved OS (384 vs 114 days, p = 0.034 and 516 vs 245 days, p = 0.001, respectively). Low postoperative NLR correlated with OS (408 vs 249 days, p = 0.029). On multivariate analysis using forward selection process, extent of resection (EOR) (GTR vs biopsy, p = 0.004 and STR vs biopsy, p = 0.011), and any previous surgery (p = 0.014) were independent prognostic biomarkers for OS. On multivariate analysis of these latter variables with literature-derived prognostic biomarkers, EOR remained significantly associated with OS (p = 0.037). Conclusions EOR, followed by having any surgery prior to GBM, are the most significant independent predictors of GBM patient’s OS. Post-operative ECOG, daily dexamethasone and IDH mutation are independent prognostic biomarkers for PFS. PNI may be superior to NLR. Post- vs pre-operative serum inflammatory marker levels may be associated with survival.
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Affiliation(s)
- Celine Garrett
- School of Medicine, Western Sydney University, Campbelltown, NSW, Australia
- Circulating Tumour Cells Group, Ingham Institute for Applied Medical Research, Liverpool, NSW, Australia
- * E-mail:
| | - Therese M. Becker
- School of Medicine, Western Sydney University, Campbelltown, NSW, Australia
- Circulating Tumour Cells Group, Ingham Institute for Applied Medical Research, Liverpool, NSW, Australia
- School of Medicine, University of New South Wales, Kingsford, NSW, Australia
| | - David Lynch
- School of Medicine, Western Sydney University, Campbelltown, NSW, Australia
- Circulating Tumour Cells Group, Ingham Institute for Applied Medical Research, Liverpool, NSW, Australia
| | - Joseph Po
- Circulating Tumour Cells Group, Ingham Institute for Applied Medical Research, Liverpool, NSW, Australia
| | - Wei Xuan
- Circulating Tumour Cells Group, Ingham Institute for Applied Medical Research, Liverpool, NSW, Australia
| | - Kieran F. Scott
- School of Medicine, Western Sydney University, Campbelltown, NSW, Australia
- Circulating Tumour Cells Group, Ingham Institute for Applied Medical Research, Liverpool, NSW, Australia
| | - Paul de Souza
- School of Medicine, Western Sydney University, Campbelltown, NSW, Australia
- Circulating Tumour Cells Group, Ingham Institute for Applied Medical Research, Liverpool, NSW, Australia
- School of Medicine, University of New South Wales, Kingsford, NSW, Australia
- School of Medicine, University of Wollongong, Wollongong, NSW, Australia
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Ali H, Harting R, de Vries R, Ali M, Wurdinger T, Best MG. Blood-Based Biomarkers for Glioma in the Context of Gliomagenesis: A Systematic Review. Front Oncol 2021; 11:665235. [PMID: 34150629 PMCID: PMC8211985 DOI: 10.3389/fonc.2021.665235] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2021] [Accepted: 05/18/2021] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Gliomas are the most common and aggressive tumors of the central nervous system. A robust and widely used blood-based biomarker for glioma has not yet been identified. In recent years, a plethora of new research on blood-based biomarkers for glial tumors has been published. In this review, we question which molecules, including proteins, nucleic acids, circulating cells, and metabolomics, are most promising blood-based biomarkers for glioma diagnosis, prognosis, monitoring and other purposes, and align them to the seminal processes of cancer. METHODS The Pubmed and Embase databases were systematically searched. Biomarkers were categorized in the identified biomolecules and biosources. Biomarker characteristics were assessed using the area under the curve (AUC), accuracy, sensitivity and/or specificity values and the degree of statistical significance among the assessed clinical groups was reported. RESULTS 7,919 references were identified: 3,596 in PubMed and 4,323 in Embase. Following screening of titles, abstracts and availability of full-text, 262 articles were included in the final systematic review. Panels of multiple biomarkers together consistently reached AUCs >0.8 and accuracies >80% for various purposes but especially for diagnostics. The accuracy of single biomarkers, consisting of only one measurement, was far more variable, but single microRNAs and proteins are generally more promising as compared to other biomarker types. CONCLUSION Panels of microRNAs and proteins are most promising biomarkers, while single biomarkers such as GFAP, IL-10 and individual miRNAs also hold promise. It is possible that panels are more accurate once these are involved in different, complementary cancer-related molecular pathways, because not all pathways may be dysregulated in cancer patients. As biomarkers seem to be increasingly dysregulated in patients with short survival, higher tumor grades and more pathological tumor types, it can be hypothesized that more pathways are dysregulated as the degree of malignancy of the glial tumor increases. Despite, none of the biomarkers found in the literature search seem to be currently ready for clinical implementation, and most of the studies report only preliminary application of the identified biomarkers. Hence, large-scale validation of currently identified and potential novel biomarkers to show clinical utility is warranted.
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Affiliation(s)
- Hamza Ali
- Department of Neurosurgery, Brain Tumor Center Amsterdam, Cancer Center Amsterdam, Amsterdam UMC, VU University Medical Center and Academic Medical Center, Amsterdam, Netherlands
| | - Romée Harting
- Department of Neurosurgery, Brain Tumor Center Amsterdam, Cancer Center Amsterdam, Amsterdam UMC, VU University Medical Center and Academic Medical Center, Amsterdam, Netherlands
| | - Ralph de Vries
- Medical Library, Vrije Universiteit, Amsterdam, Netherlands
| | - Meedie Ali
- Department of Neurosurgery, Brain Tumor Center Amsterdam, Cancer Center Amsterdam, Amsterdam UMC, VU University Medical Center and Academic Medical Center, Amsterdam, Netherlands
| | - Thomas Wurdinger
- Department of Neurosurgery, Brain Tumor Center Amsterdam, Cancer Center Amsterdam, Amsterdam UMC, VU University Medical Center and Academic Medical Center, Amsterdam, Netherlands
| | - Myron G. Best
- Department of Neurosurgery, Brain Tumor Center Amsterdam, Cancer Center Amsterdam, Amsterdam UMC, VU University Medical Center and Academic Medical Center, Amsterdam, Netherlands
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24
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Jia T, Zhang R, Kong F, Zhang Q, Xi Z. The Prognostic Role and Nomogram Establishment of a Novel Prognostic Score Combining with Fibrinogen and Albumin Levels in Patients with WHO Grade II/III Gliomas. Int J Gen Med 2021; 14:2137-2145. [PMID: 34093034 PMCID: PMC8169085 DOI: 10.2147/ijgm.s303733] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2021] [Accepted: 05/14/2021] [Indexed: 12/12/2022] Open
Abstract
Purpose World Health Organization (WHO) Grades II and III gliomas [also known as low grade gliomas (LGGs)] displayed different malignant behaviors and survival outcomes compared to Grade IV gliomas. This study aimed to identify the prognostic predictive value of a novel cumulative prognostic score [combined with fibrinogen and albumin levels (FA score)], establish and validate a point-based nomogram in LGG patients. Patients and Methods A total of 91 patients who underwent total glioma resection at Shengjing Hospital of China Medical University between 2011 and 2013 were enrolled to establish a prognostic nomogram. All patients were histologically diagnosed as grades II/III, and never received radiotherapy or chemotherapy before surgery. Data collection included patient characteristics, clinicopathological factors, and preoperative hematology results. The performance of the nomogram was subsequently validated by the concordance index (c-index), calibration curve, and receiver operating characteristic (ROC) curve. Results The FA score was negatively associated with the overall survival (OS) of LGG patients (p < 0.001). The results of multivariate analysis showed that FA score [p = 0.006, HR = 1.92, 95% confidence interval (CI): 1.21–3.05], age (p = 0.002, HR = 3.014, 95% CI:1.52–5.97), and white blood count (p < 0.001, HR = 4.24, 95% CI: 2.08–8.67) were independent prognostic factors for overall survival (OS). The study established a nomogram to predict OS with a c-index of 0.783 (95% CI, 0.72–0.84). Conclusion FA score might be a potential prognostic biomarker for LGG patients, and a reliable point-based nomogram will help clinicians to decide on the best treatment plans.
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Affiliation(s)
- Tianshu Jia
- Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, People's Republic of China
| | - Rui Zhang
- Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, People's Republic of China
| | - Fanfei Kong
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, People's Republic of China
| | - Qianjiao Zhang
- Pain Department, The People's Hospital of Liaoning Province, Shenyang, People's Republic of China
| | - Zhuo Xi
- Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, People's Republic of China
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Research Supporting a Pilot Study of Metronomic Dapsone during Glioblastoma Chemoirradiation. Med Sci (Basel) 2021; 9:medsci9010012. [PMID: 33669324 PMCID: PMC7931060 DOI: 10.3390/medsci9010012] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2021] [Revised: 02/08/2021] [Accepted: 02/10/2021] [Indexed: 12/13/2022] Open
Abstract
This short note presents previous research data supporting a pilot study of metronomic dapsone during the entire course of glioblastoma treatment. The reviewed data indicate that neutrophils are an integral part of human glioblastoma pathophysiology, contributing to or facilitating glioblastoma growth and treatment resistance. Neutrophils collect within glioblastoma by chemotaxis along several chemokine/cytokine gradients, prominently among which is interleukin-8. Old data from dermatology research has shown that the old and inexpensive generic drug dapsone inhibits neutrophils' chemotaxis along interleukin-8 gradients. It is on that basis that dapsone is used to treat neutrophilic dermatoses, for example, dermatitis herpetiformis, bullous pemphigoid, erlotinib-related rash, and others. The hypothesis of this paper is that dapsone will reduce glioblastomas' neutrophil accumulations by the same mechanisms by which it reduces dermal neutrophil accumulations in the neutrophilic dermatoses. Dapsone would thereby reduce neutrophils' contributions to glioblastoma growth. Dapsone is not an ideal drug, however. It generates methemoglobinemia that occasionally is symptomatic. This generation is reduced by concomitant use of the antacid drug cimetidine. Given the uniform lethality of glioblastoma as of 2020, the risks of dapsone 100 mg twice daily and cimetidine 400 mg twice daily is low enough to warrant a judicious pilot study.
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Kuranari Y, Tamura R, Tsuda N, Kosugi K, Morimoto Y, Yoshida K, Toda M. Prognostic Significance of Preoperative Neutrophil-to-Lymphocyte Ratio in Patients With Meningiomas. Front Oncol 2020; 10:592470. [PMID: 33330078 PMCID: PMC7732694 DOI: 10.3389/fonc.2020.592470] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2020] [Accepted: 10/26/2020] [Indexed: 12/12/2022] Open
Abstract
Background Meningiomas are the most common benign intracranial tumors. However, even WHO grade I meningiomas occasionally show local tumor recurrence. Prognostic factors for meningiomas have not been fully established. Neutrophil-to-lymphocyte ratio (NLR) has been reported as a prognostic factor for several solid tumors. The prognostic value of NLR in meningiomas has been analyzed in few studies. Materials and Methods This retrospective study included 160 patients who underwent surgery for meningiomas between October 2010 and September 2017. We analyzed the associations between patients’ clinical data (sex, age, primary/recurrent, WHO grade, extent of removal, tumor location, peritumoral brain edema, and preoperative laboratory data) and clinical outcomes, including recurrence and progression-free survival (PFS). Results Forty-four meningiomas recurred within the follow-up period of 3.8 years. WHO grade II, III, subtotal removal, history of recurrence, Ki-67 labeling index ≥3.0, and preoperative NLR value ≥2.6 were significantly associated with shorter PFS (P < 0.001, < 0.001, 0.002, < 0.001, and 0.015, respectively). Furthermore, NLR ≥ 2.6 was also significantly associated with shorter PFS in a subgroup analysis of WHO grade I meningiomas (P = 0.003). In univariate and multivariate analyses, NLR ≥2.6 remained as a significant predictive factor for shorter PFS in patients with meningioma (P = 0.014). Conclusions NLR may be a cost-effective and novel preoperatively usable biomarker in patients with meningiomas.
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Affiliation(s)
- Yuki Kuranari
- Department of Neurosurgery, Keio University School of Medicine, Tokyo, Japan
| | - Ryota Tamura
- Department of Neurosurgery, Keio University School of Medicine, Tokyo, Japan
| | - Noboru Tsuda
- Department of Pathology, Keio University School of Medicine, Tokyo, Japan
| | - Kenzo Kosugi
- Department of Neurosurgery, Keio University School of Medicine, Tokyo, Japan
| | - Yukina Morimoto
- Department of Neurosurgery, Keio University School of Medicine, Tokyo, Japan
| | - Kazunari Yoshida
- Department of Neurosurgery, Keio University School of Medicine, Tokyo, Japan
| | - Masahiro Toda
- Department of Neurosurgery, Keio University School of Medicine, Tokyo, Japan
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Khayat Kashani HR, Azhari S, Nayebaghayee H, Salimi S, Mohammadi HR. Prediction value of preoperative findings on meningioma grading using artificial neural network. Clin Neurol Neurosurg 2020; 196:105947. [PMID: 32521393 DOI: 10.1016/j.clineuro.2020.105947] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2020] [Revised: 05/17/2020] [Accepted: 05/18/2020] [Indexed: 11/26/2022]
Abstract
OBJECTIVES Meningioma is the most common brain tumor in adults. Grade 1 meningiomas have excellent prognoses, but grades 2 and 3 usually have worse outcomes, higher recurrence rates, and higher mortality rates. Preoperative determination of tumor grade may be helpful in deciding the type of surgery and the rate of resection. Blood markers have been used to predict the rate of malignancy and prognosis of tumors in different regions, including the brain. The current study investigated the use of blood markers on predicting meningioma grade. PATIENTS AND METHODS Patients with newly diagnosed meningiomas were retrospectively reviewed. Data on the patients' demographics, tumor locations, blood markers, and tumor pathology grades was extracted. The relationship between preoperative findings and tumor grade was statistically analyzed, and using the same findings and an artificial neural network, the accuracy of tumor grade prediction was evaluated. RESULTS This study included 95 patients, 69 cases (72.4 %) of grade 1, 23 cases of grade 2 (24.4 %) and 3 cases of grade 3 (3.2 %) meningiomas. Monocyte and neutrophil counts as well as lymphocyte-to-monocyte ratio (LMR) were significantly different between low grade and high grade meningiomas, with higher monocyte and neutrophil counts and higher LMR associated with high grade meningiomas (p < 0.05). Evaluation of the data with an artificial neural network using RBF with 5 variables (age, monocyte count, LMR, platelet-to-lymphocyte ratio (PLR), and neutrophil count) indicated that tumor grade can be determined with 83 % accuracy using an artificial neural network. CONCLUSION A preoperative high monocyte count and high LMR are associated with high grade meningioma. An artificial neural network using preoperative data can acceptably be used to characterize meningioma tumor grades.
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Affiliation(s)
- Hamid Reza Khayat Kashani
- Department of Neurosurgery, Imam Hossein Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Shirzad Azhari
- Department of Neurosurgery, Imam Hossein Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hossein Nayebaghayee
- Department of Neurosurgery, Imam Hossein Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Sohrab Salimi
- Clinical Research and Development Unit, Imam Hossein Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Development Unit, Imam Hossein Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hasan Reza Mohammadi
- Department of Neurosurgery, Imam Hossein Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Cho A, Czech T, Wang WT, Dodier P, Reinprecht A, Bavinzski G. Peri-interventional Behavior of the Neutrophil to Lymphocyte Ratio in Patients with Intracranial Aneurysms. World Neurosurg 2020; 141:e223-e230. [PMID: 32434035 DOI: 10.1016/j.wneu.2020.05.084] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2020] [Revised: 05/08/2020] [Accepted: 05/09/2020] [Indexed: 02/07/2023]
Abstract
OBJECTIVE The neutrophil-to-lymphocyte ratio (NLR) has been investigated as an independent predictive marker for clinical outcomes in vascular diseases. This study aimed to investigate the peri-interventional behavior of the NLR in patients with ruptured and unruptured intracranial aneurysms (IAs). METHODS A total of 117 patients with IAs, who were treated at our department and had available complete data, were retrospectively identified during a 10-year period. Routine laboratory parameters, including the neutrophil and lymphocytes counts, were evaluated before and after treatment. RESULTS The baseline NLR showed significant differences between patients with ruptured and unruptured IAs (6.3 vs. 1.8; P < 0.001). In patients with ruptured IAs, the baseline NLR decreased significantly during the follow-up visits, whereas in unruptured IAs, the NLR remained low. Furthermore, higher baseline NLR values could also be observed in patients with ruptured IAs and fatal outcome than in surviving patients (8.0 vs. 5.4; P = 0.220). In patients with poor functional outcome, defined as modified Rankin score ≥3, the NLR was significantly higher before treatment (P = 0.047), at day 10 (P = 0.025), and 1 month after treatment (P = 0.001). CONCLUSIONS The peri-interventional NLR was significantly different between patients with ruptured and unruptured IAs. In patients with ruptured IAs, elevated baseline NLR levels were associated with poor postoperative functional outcomes and decreased postoperatively, implying the potential prognostic value of NLR in patients with IAs.
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Affiliation(s)
- Anna Cho
- Department of Neurosurgery, Vienna General Hospital, Medical University of Vienna, Vienna, Austria
| | - Thomas Czech
- Department of Neurosurgery, Vienna General Hospital, Medical University of Vienna, Vienna, Austria
| | - Wei-Te Wang
- Department of Neurosurgery, Vienna General Hospital, Medical University of Vienna, Vienna, Austria
| | - Philippe Dodier
- Department of Neurosurgery, Vienna General Hospital, Medical University of Vienna, Vienna, Austria
| | - Andrea Reinprecht
- Department of Neurosurgery, Vienna General Hospital, Medical University of Vienna, Vienna, Austria
| | - Gerhard Bavinzski
- Department of Neurosurgery, Vienna General Hospital, Medical University of Vienna, Vienna, Austria.
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Role of Neutrophils and Myeloid-Derived Suppressor Cells in Glioma Progression and Treatment Resistance. Int J Mol Sci 2020; 21:ijms21061954. [PMID: 32182988 PMCID: PMC7139844 DOI: 10.3390/ijms21061954] [Citation(s) in RCA: 66] [Impact Index Per Article: 13.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2020] [Revised: 02/29/2020] [Accepted: 03/05/2020] [Indexed: 02/07/2023] Open
Abstract
Recent efforts in brain tumor research have been directed towards the modulation of the immune system for therapeutic interventions. Several human cancers, including gliomas, are infiltrated with immune cell types-including neutrophils and myeloid-derived suppressor cells-that contribute to tumor progression, invasiveness, and treatment resistance. The role of tumor-associated neutrophils and myeloid-derived suppressor cells in cancer biology remains elusive, as these cells can exert a multitude of pro-tumor and antitumor effects. In this review, we provide the current understanding and novel insights on the role of neutrophils and myeloid-derived suppressor cells in glioma progression and treatment resistance, as well as the mechanisms of pleiotropic behaviors in these cells during disease progression, with an emphasis on possible strategies to reprogram these cells towards their antitumor actions.
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Tan Z, Shen L, Wu H, Deng L, Li Z, Huang X. Preoperative Neutrophil/Lymphocyte Ratio Is an Independent Prognostic Biomarker in Patients with Low-Grade Gliomas. World Neurosurg 2019; 132:e585-e590. [PMID: 31442642 DOI: 10.1016/j.wneu.2019.08.068] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2019] [Revised: 08/07/2019] [Accepted: 08/09/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND There are no standardized criteria to predict the prognosis of patients with low-grade gliomas. Therefore, novel prognostic biomarkers that can guide follow-up schedules and therapeutic approaches urgently are required in patients with low-grade gliomas. METHODS One hundred nineteen patients with World Health Organization (WHO) II gliomas were recruited between January 2010 and December 2016 from Xiangya Hospital for this study. We collected neutrophil and lymphocyte values from the full blood counts measured 24 h before surgery. Neutrophil-to-lymphocyte ratios (NLRs) were then calculated. The significance of the NLR was determined based on a nonparametric test. The Kaplan-Meier method was used to estimate survival rates. The influence of the NLR on progression-free survival and overall survival was evaluated using univariate and multivariate Cox proportional hazards models. RESULTS Preoperative NLRs were upregulated in patients with WHO II gliomas who relapsed or died. Preoperative NLRs were also significantly correlated with age, preoperative neutrophil values, and preoperative lymphocyte values. Compared with the low preoperative NLR group, patients with WHO II gliomas in the high preoperative NLR group had significantly higher relapse and lower survival rates. In addition, the preoperative NLR and tumor type were independent prognostic parameters of progression-free survival for WHO II gliomas, whereas only the preoperative NLR was an independent prognostic parameter of overall survival for WHO II gliomas. CONCLUSIONS High preoperative NLRs were significantly associated with greater relapse and poor prognosis in patients with WHO II gliomas.
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Affiliation(s)
- Zhaohua Tan
- Department of Oncology, Xiangya Hospital, Central South University, Changsha, China
| | - Liangfang Shen
- Department of Oncology, Xiangya Hospital, Central South University, Changsha, China
| | - Haijun Wu
- Department of Oncology, Xiangya Hospital, Central South University, Changsha, China
| | - Liang Deng
- Department of Oncology, Xiangya Hospital, Central South University, Changsha, China
| | - Zhanzhan Li
- Department of Oncology, Xiangya Hospital, Central South University, Changsha, China
| | - Xinqiong Huang
- Department of Oncology, Xiangya Hospital, Central South University, Changsha, China.
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Lei YY, Li YT, Hu QL, Wang J, Sui AX. Prognostic impact of neutrophil-to-lymphocyte ratio in gliomas: a systematic review and meta-analysis. World J Surg Oncol 2019; 17:152. [PMID: 31472673 PMCID: PMC6717646 DOI: 10.1186/s12957-019-1686-5] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2019] [Accepted: 08/06/2019] [Indexed: 02/07/2023] Open
Abstract
Background In some malignant tumors, a high neutrophil-to-lymphocyte ratio (NLR) is connected with unfavorable prognosis. Nevertheless, the prognostic value of the NLR in gliomas remains disputed. The clinical significance of the NLR in gliomas was investigated in our study. Methods The databases, PubMed, Embase, and the Cochrane Library, were searched using words like “glioma,” “glioblastoma,” “neutrophil-to-lymphocyte ratio,” and others through May 2019. We evaluated the significance of NLR on overall survival (OS) of patients with gliomas in our study. Results Finally, 16 cohorts with 2275 patients were analyzed. The pooled analysis revealed that an elevated NLR was connected with unfavorable OS (hazards ratio (HR): 1.43, 95% confidence interval (CI): 1.27–1.62) outcomes of patients with gliomas. Conclusion A high NLR can be considered a high-risk prognostic factor in gliomas, and more adjuvant chemotherapy should be recommended for high-risk patients. Electronic supplementary material The online version of this article (10.1186/s12957-019-1686-5) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Yu-Ying Lei
- Department of Oncology, Hebei General Hospital, Shijiazhuang, 050051, Hebei, China
| | - Yi-Tong Li
- Department of Oncology, Hebei General Hospital, Shijiazhuang, 050051, Hebei, China
| | - Qi-Lu Hu
- Department of Oncology, Hebei General Hospital, Shijiazhuang, 050051, Hebei, China
| | - Juan Wang
- Department of Oncology, Hebei General Hospital, Shijiazhuang, 050051, Hebei, China
| | - Ai-Xia Sui
- Department of Oncology, Hebei General Hospital, Shijiazhuang, 050051, Hebei, China.
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