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Shi Y, Zhao X, Zhou Y, Zhang X. Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio as predictive biomarkers for treatment response in primary advanced hypopharyngeal squamous cell carcinoma treated with chemoimmunotherapy. Clin Exp Med 2025; 25:172. [PMID: 40411692 PMCID: PMC12103357 DOI: 10.1007/s10238-025-01675-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2024] [Accepted: 04/07/2025] [Indexed: 05/26/2025]
Abstract
To evaluate the predictive value of the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in peripheral blood for assessing the treatment response to chemoimmunotherapy in primary advanced hypopharyngeal squamous cell carcinoma (HPSCC), we retrospectively reviewed the medical records of patients treated with neoadjuvant taxane-platinum (TP) chemotherapy plus an anti-programmed cell death-1 (PD-1) inhibitor at Wuhan Union Hospital from Jan 2020 to Dec 2022. We collected data on absolute neutrophil, lymphocyte, and platelet counts from routine blood tested at baseline and within a week after the first treatment. A total of 35 patients were included in this study. Post-treatment NLR (rs = - 0.445, p = 0.007) and PLR (rs = - 0.475, p = 0.004) demonstrated negative correlations with treatment response assessed by the Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1). NLR and PLR were significantly lower in patients achieving a complete response than those not achieving it (with p values of 0.04 and 0.02 for NLR and PLR, respectively). Among the 27 patients who underwent radical surgery following three cycles of chemoimmunotherapy, a high PLR after the first treatment was negatively correlated with attaining a pathological complete response (pCR) (rs = - 0.424, p = 0.028). For predicting pCR, the receiver operating characteristic (ROC) curve of PLR after the first treatment yielded an area under the curve (AUC) of 0.759 (95% confidence interval [CI]: 0.572-0.946, p = 0.031), with a sensitivity of 77.8% and a specificity of 72.2%. This research underscores the predictive value of the NLR and PLR in appraising not only the treatment response, as gauged by the RECIST 1.1, but also the pathological response to chemoimmunotherapy in patients with HPSCC.
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Affiliation(s)
- Yueyue Shi
- Department of Otolaryngology and Head and Neck Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Xueyan Zhao
- Department of Otolaryngology and Head and Neck Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Yan Zhou
- Department of Otolaryngology and Head and Neck Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Xiaomeng Zhang
- Department of Otolaryngology and Head and Neck Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
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Aykan MB, Bölek H, Yekedüz E, Sertesen E, Tural D, Karaçin C, Şendur MAN, Uçar G, Arslan Ç, Işık S, Sim S, Sever ÖN, Hacıoğlu B, Sezgin Göksu S, Özgüroğlu M, Karadurmuş N, Ürün Y. Navigating second-line therapy in metastatic renal cell carcinoma: a comparative analysis of immune checkpoint inhibitors and tyrosine kinase inhibitors: a study of Turkish Oncology Group Kidney Cancer Consortium. Ther Adv Med Oncol 2025; 17:17588359251331540. [PMID: 40297625 PMCID: PMC12035120 DOI: 10.1177/17588359251331540] [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: 08/23/2024] [Accepted: 03/13/2025] [Indexed: 04/30/2025] Open
Abstract
Background Despite progress in treatment, many metastatic renal cell carcinoma (mRCC) patients still experience progression after first-line tyrosine kinase inhibitor (TKI), necessitating effective second-line options. While guidelines endorse combination therapies, accessibility limitations often restrict therapy to TKI monotherapy. Objectives Existing decision-making relies on limited evidence, lacking direct comparisons between the leading second-line options (cabozantinib and nivolumab) which surpass everolimus in advanced mRCC. To address this gap, this study compares the efficacy of TKI versus nivolumab in second line while investigating factors influencing outcomes. Design This was a retrospective cohort study. Methods Turkish Oncology Group Kidney Cancer Consortium includes more than 1000 mRCC patients from 13 centers in Türkiye. It has the largest national data. We extracted 214 patients treated with a TKI in the first line and nivolumab or TKI in the second line. Results The median overall survival (OS) and time to treatment failure (TTF) were similar in the TKI-TKI and TKI-immune checkpoint inhibitor (ICI; 41.1 and 44.8 months, p = 0.446 for OS; 27.4 and 29.8 months, p = 0.857 for TTF). The presence of previous nephrectomy for TTF made a significant difference in univariable and multivariable analysis. Bone metastases negatively affected TTF in both univariable and multivariable analyses. In the neutrophil-to-lymphocyte ratio (NLR)-high group, OS and TTF were longer in patients treated with TKI-ICI than in the TKI-TKI. In multivariable analysis, NLR was an independent prognostic factor for OS and TTF to select ICI in the second-line. Conclusion Our analysis revealed no significant difference in OS between patients receiving ICIs or TKIs as second-line therapy. In the subgroup of patients with elevated NLR, ICI therapy was found to cause no improvement in OS. This finding suggests the potential utility of NLR as a biomarker to guide targeted selection of ICI therapy among patients progressing after first-line TKIs. Furthermore, our study identified other noteworthy prognostic factors influencing outcomes, including the presence of bone or liver metastases, Eastern Cooperative Oncology Group performance status, and International Metastatic Renal Cell Carcinoma Database Consortium risk score.
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Affiliation(s)
- Musa Barış Aykan
- Department of Medical Oncology, Gulhane Faculty of Medicine, Health Sciences University, Ankara, Turkey
| | - Hatice Bölek
- Department of Medical Oncology, Ankara University School of Medicine, Ankara, Turkey
| | - Emre Yekedüz
- Department of Medical Oncology, Ankara University School of Medicine, Ankara, Turkey
| | - Elif Sertesen
- Department of Medical Oncology, Dr Abdurrahman Yurtaslan Ankara Oncology Training and Research Hospital, Ankara, Turkey
| | - Deniz Tural
- Department of Medical Oncology, Koc University Hospital, Istanbul, Turkey
| | - Cengiz Karaçin
- Department of Medical Oncology, Dr Abdurrahman Yurtaslan Ankara Oncology Training and Research Hospital, Ankara, Turkey
| | - Mehmet Ali Nahit Şendur
- Department of Medical Oncology, Yildirim Beyazit University Faculty of Medicine, Ankara, Turkey
| | - Gökhan Uçar
- Department of Medical Oncology, Ministry of Health, Ankara Bilkent City Hospital, Ankara, Turkey
| | - Çağatay Arslan
- Department of Medical Oncology, Izmir Ekonomi Universitesi (Izmir University of Economics), Izmir, Turkey
| | - Selver Işık
- Department of Medical Oncology, Faculty of Medicine, Marmara University, Istanbul, Turkey
| | - Saadet Sim
- Department of Medical Oncology, Faculty of Medicine, Ege University, Izmir, Turkey
| | - Özlem Nuray Sever
- Department of Medical Oncology, Kartal Dr Lutfi Kirdar City Hospital, Istanbul, Turkey
| | - Bekir Hacıoğlu
- Department of Medical Oncology, Faculty of Medicine, Trakya University, Edirne, Turkey
| | - Sema Sezgin Göksu
- Department of Medical Oncology, Faculty of Medicine, Akdeniz University, Antalya, Turkey
| | - Mustafa Özgüroğlu
- Department of Medical Oncology, İstanbul Üniversitesi-Cerrahpaşa Cerrahpaşa Tıp Fakültesi (Istanbul University-Cerrahpaşa Cerrahpaşa Medical Faculty), Istanbul, Turkey
| | - Nuri Karadurmuş
- Department of Medical Oncology, Gulhane Faculty of Medicine, Health Sciences University, Ankara, Turkey
| | - Yüksel Ürün
- Department of Medical Oncology, Faculty of Medicine, Cebeci Hospital, Ankara University, 06590, Cebeci/Ankara, Turkey
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Chen W, Xu G, Yan X, Wang S, Xie Q, Liu Q, Zheng B, Chen C, Zhu Y, Yang Z. Naples Prognostic Score as a Novel Prognostic Prediction Tool for Resectable Locally Advanced Esophageal Squamous Cell Carcinoma After Neoadjuvant Therapy. J Inflamm Res 2025; 18:4843-4856. [PMID: 40230436 PMCID: PMC11994464 DOI: 10.2147/jir.s502058] [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: 10/31/2024] [Accepted: 03/28/2025] [Indexed: 04/16/2025] Open
Abstract
Purpose Esophageal squamous cell carcinoma (ESCC) is a highly invasive malignancy with poor prognosis, especially in its locally advanced stages. Recent studies have highlighted the role of inflammation and nutrition in cancer prognosis. The Naples prognostic score (NPS), which integrates inflammatory and nutritional markers, has demonstrated prognostic value in various cancers. However, its applicability in patients with resectable locally advanced ESCC after neoadjuvant therapy remains unexplored. This study aimed to evaluate the prognostic value of the NPS in predicting overall survival (OS) and progression-free survival (PFS) in these patients. Patients and Methods A retrospective study was conducted on 175 patients with locally advanced ESCC who underwent neoadjuvant therapy followed by surgical resection at Fujian Medical University Union Hospital between 2016-2020. Patients were grouped by NPS scores (0,1-2,3-4). Survival analysis was performed using the Kaplan-Meier method, and the predictive accuracy of NPS was evaluated using receiver operating characteristic (ROC) curves. Cox proportional hazards regression models were used to identify independent prognostic factors for OS and PFS. Results Significant differences in OS (p=0.0025) and PFS (p=0.0018) were observed across the three NPS groups. Multivariable Cox regression analysis confirmed that patients with higher NPS scores (NPS group 2) had significantly worse OS (HR = 2.768, 95% CI: 1.239-6.183, p = 0.013) and PFS (HR = 3.345, 95% CI: 1.574-7.109, p = 0.002). The area under the curve (AUC) for NPS was 0.63 for OS and 0.67 for PFS, indicating moderate predictive value. Conclusion The NPS is a simple and effective prognostic tool for assessing survival outcomes in patients with resectable locally advanced ESCC following neoadjuvant therapy. Its integration into clinical practice may aid in better stratification and treatment decision-making for these patients.
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Affiliation(s)
- Weiming Chen
- Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, People’s Republic of China
- Key Laboratory of Cardio-Thoracic Surgery (Fujian Medical University), Fuzhou, Fujian, People’s Republic of China
- Clinical Research Center for Thoracic Tumors of Fujian Province, Fuzhou, Fujian, People’s Republic of China
| | - Guobing Xu
- Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, People’s Republic of China
- Key Laboratory of Cardio-Thoracic Surgery (Fujian Medical University), Fuzhou, Fujian, People’s Republic of China
- Clinical Research Center for Thoracic Tumors of Fujian Province, Fuzhou, Fujian, People’s Republic of China
| | - Xin Yan
- Department of Cardiac Medical Center Nursing, Fujian Medical University Union Hospital, Fuzhou, Fujian, People’s Republic of China
| | - Shuo Wang
- Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, People’s Republic of China
- Key Laboratory of Cardio-Thoracic Surgery (Fujian Medical University), Fuzhou, Fujian, People’s Republic of China
- Clinical Research Center for Thoracic Tumors of Fujian Province, Fuzhou, Fujian, People’s Republic of China
| | - Qichang Xie
- Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, People’s Republic of China
- Key Laboratory of Cardio-Thoracic Surgery (Fujian Medical University), Fuzhou, Fujian, People’s Republic of China
- Clinical Research Center for Thoracic Tumors of Fujian Province, Fuzhou, Fujian, People’s Republic of China
| | - Qing Liu
- Oncology Department of Fujian Medical university Union Hospital, Fuzhou, Fujian, People’s Republic of China
| | - Bin Zheng
- Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, People’s Republic of China
- Key Laboratory of Cardio-Thoracic Surgery (Fujian Medical University), Fuzhou, Fujian, People’s Republic of China
- Clinical Research Center for Thoracic Tumors of Fujian Province, Fuzhou, Fujian, People’s Republic of China
| | - Chun Chen
- Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, People’s Republic of China
- Key Laboratory of Cardio-Thoracic Surgery (Fujian Medical University), Fuzhou, Fujian, People’s Republic of China
- Clinical Research Center for Thoracic Tumors of Fujian Province, Fuzhou, Fujian, People’s Republic of China
| | - Yong Zhu
- Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, People’s Republic of China
- Key Laboratory of Cardio-Thoracic Surgery (Fujian Medical University), Fuzhou, Fujian, People’s Republic of China
- Clinical Research Center for Thoracic Tumors of Fujian Province, Fuzhou, Fujian, People’s Republic of China
| | - Zhang Yang
- Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, People’s Republic of China
- Key Laboratory of Cardio-Thoracic Surgery (Fujian Medical University), Fuzhou, Fujian, People’s Republic of China
- Clinical Research Center for Thoracic Tumors of Fujian Province, Fuzhou, Fujian, People’s Republic of China
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Dong L, Ma Y, Cao G, Chen D, Dong F, Jiao X, Cao Y, Liu C, Wang Y, Zhuo N, Wang F, Guo Y, Dai T, Zhang S, Jiao H, Zou X, Li J, Shen L, He Z, Zhang Y, Lu Z. An integrated prognosis prediction model based on real-word clinical characteristics for immunotherapy in advanced esophageal squamous cell carcinoma. Cancer Immunol Immunother 2025; 74:112. [PMID: 39998564 PMCID: PMC11861846 DOI: 10.1007/s00262-025-03963-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2025] [Accepted: 01/29/2025] [Indexed: 02/27/2025]
Abstract
INTRODUCTION Immune checkpoint inhibitors (ICIs) benefit only a subset of patients in advanced esophageal squamous cell carcinoma (ESCC). Our study aims to develop and validate a clinically accessible model to better identify those who may respond to ICIs. METHODS This study enrolled advanced ESCC patients treated with ICIs at Peking University Cancer Hospital from January 14, 2016, to January 26, 2024 for the training cohort and at Harbin Medical University Cancer Hospital between January 10, 2019, and July 6, 2022 for the validation cohort. Combined positive score (CPS) was recorded to assess the predictive value of programmed cell death ligand-1 (PD-L1). Baseline clinical and laboratory characteristics were identified as predictors through Akaike information criterion (AIC) and Cox proportional hazards regression. The prediction model underwent internal validation through bootstrapping and was externally validated in the validation cohort. RESULTS The training cohort consisted of 430 patients, while the validation cohort included 184 patients. PD-L1 expression failed to discriminate survival outcomes. The prediction model incorporates 10 variables: stage, bone metastasis, line of therapy, treatment, lactate dehydrogenase, carcinoembryonic antigen, carbohydrate antigen 199, systemic immune-inflammation index, lymphocyte count and prognostic nutritional index. The model achieved a C-index of 0.725 in the training cohort, 0.722 following bootstrapping, and 0.691 in the external validation cohort. An interactive online prediction tool ( https://escc-survival.shinyapps.io/shiny_app/ ) was subsequently developed. CONCLUSIONS This is the first large-scale, real-world model for individualized survival prediction for advanced ESCC patients treated with ICIs, offering a practical tool for optimizing clinical decisions.
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Affiliation(s)
- Liyuan Dong
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing, 100142, China
| | - Yue Ma
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing, 100142, China
- Department of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, 150081, China
| | - Guang Cao
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Interventional Therapy, Peking University Cancer Hospital & Institute, Beijing, 100142, China
| | - Dongze Chen
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Genetics, Peking University Cancer Hospital & Institute, Beijing, 100142, China
| | - Fengxiao Dong
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing, 100142, China
| | - Xi Jiao
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing, 100142, China
| | - Yanshuo Cao
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing, 100142, China
| | - Chang Liu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing, 100142, China
| | - Yanni Wang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing, 100142, China
| | - Na Zhuo
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing, 100142, China
| | - Fengyuan Wang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing, 100142, China
| | - Yixuan Guo
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing, 100142, China
| | - Tingting Dai
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing, 100142, China
| | - Shuwei Zhang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing, 100142, China
| | - Hao Jiao
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing, 100142, China
| | - Xingyue Zou
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing, 100142, China
| | - Jian Li
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing, 100142, China
| | - Lin Shen
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing, 100142, China
| | - Zhonghu He
- State Key Laboratory of Molecular Oncology, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Genetics, Peking University Cancer Hospital & Institute, Beijing, 100142, China.
| | - Yanqiao Zhang
- Department of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, 150081, China.
| | - Zhihao Lu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing, 100142, China.
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Ezdoglian A, Tsang-A-Sjoe M, Khodadust F, Burchell G, Jansen G, de Gruijl T, Labots M, van der Laken CJ. Monocyte-related markers as predictors of immune checkpoint inhibitor efficacy and immune-related adverse events: a systematic review and meta-analysis. Cancer Metastasis Rev 2025; 44:35. [PMID: 39982537 PMCID: PMC11845441 DOI: 10.1007/s10555-025-10246-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2024] [Accepted: 01/22/2025] [Indexed: 02/22/2025]
Abstract
The efficacy and off-target effects of immune checkpoint inhibitors (ICI) in cancer treatment vary among patients. Monocytes likely contribute to this heterogeneous response due to their crucial role in immune homeostasis. We conducted a systematic review and meta-analysis to evaluate the impact of monocytes on ICI efficacy and immune-related adverse events (irAEs) in patients with cancer. We systematically searched PubMed, Web of Science, and Embase for clinical studies from January 2000 to December 2023. Articles were included if they mentioned cancer, ICI, monocytes, or any monocyte-related terminology. Animal studies and studies where ICIs were combined with other biologics were excluded, except for studies where two ICIs were used. This systematic review was registered with PROSPERO (CRD42023396297) prior to data extraction and analysis. Monocyte-related markers, such as absolute monocyte count (AMC), monocyte/lymphocyte ratio (MLR), specific monocyte subpopulations, and m-MDSCs were assessed in relation to ICI efficacy and safety. Bayesian meta-analysis was conducted for AMC and MLR. The risk of bias assessment was done using the Cochrane-ROBINS-I tool. Out of 5787 studies identified in our search, 155 eligible studies report peripheral blood monocyte-related markers as predictors of response to ICI, and 32 of these studies describe irAEs. Overall, based on 63 studies, a high MLR was a prognostic biomarker for short progression-free survival (PFS) and overall survival (OS) hazard ratio (HR): 1.5 (95% CI: 1.21-1.88) and 1.52 (95% CI:1.13-2.08), respectively. The increased percentage of classical monocytes was an unfavorable predictor of survival, while low baseline rates of monocytic myeloid-derived suppressor cells (m-MDSCs) were favorable. Elevated intermediate monocyte frequencies were associated but not significantly correlated with the development of irAEs. Baseline monocyte phenotyping may serve as a composite biomarker of response to ICI; however, more data is needed regarding irAEs. Monocyte-related variables may aid in risk assessment and treatment decision strategies for patients receiving ICI in terms of both efficacy and safety.
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Affiliation(s)
- Aiarpi Ezdoglian
- Department of Rheumatology and Clinical Immunology, Amsterdam University Medical Center, Amsterdam, The Netherlands
| | - Michel Tsang-A-Sjoe
- Department of Rheumatology and Clinical Immunology, Amsterdam University Medical Center, Amsterdam, The Netherlands
| | - Fatemeh Khodadust
- Department of Rheumatology and Clinical Immunology, Amsterdam University Medical Center, Amsterdam, The Netherlands
| | - George Burchell
- Amsterdam University Medical Library, Amsterdam, The Netherlands
| | - Gerrit Jansen
- Department of Rheumatology and Clinical Immunology, Amsterdam University Medical Center, Amsterdam, The Netherlands
| | - Tanja de Gruijl
- Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam University Medical Center, Location Vrije Universiteit, Amsterdam, The Netherlands
| | - Mariette Labots
- Department of Medical Oncology, Amsterdam University Medical Center, Location Vrije Universiteit, Amsterdam, The Netherlands
| | - Conny J van der Laken
- Department of Rheumatology and Clinical Immunology, Amsterdam University Medical Center, Amsterdam, The Netherlands.
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Deng M, Qing Y, Qiu D, Sheng Y, Zhou J, Sun L. The prognostic value of pretreatment neutrophil-lymphocyte ratio and platelet-lymphocyte ratio in patients with esophageal cancer undergoing immunotherapy: a systematic review and meta-analysis. Front Oncol 2025; 15:1536920. [PMID: 40027124 PMCID: PMC11868166 DOI: 10.3389/fonc.2025.1536920] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2024] [Accepted: 01/22/2025] [Indexed: 03/05/2025] Open
Abstract
Background Esophageal cancer (EC) is associated with a high morbidity and mortality rate. Immunotherapy has demonstrated effective antitumor activity in patients with EC, making it imperative to investigate easily accessible prognostic factors. Consequently, we conducted a meta-analysis to explore the prognostic significance of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in EC patients treated with immunotherapy. Methods The literature search was conducted across three databases: PubMed, Embase, and Web of Science. The primary deadline for literature retrieval was July 2024. Hazard ratio (HR) with a 95% confidence interval (CI) was utilized to assess the association between NLR or PLR and overall survival (OS) as well as progression-free survival (PFS). Statistical analysis was performed using Review Manager version 5.4 and STATA version 15.0. Results The meta-analysis included a total of 16 studies involving 1,481 patients. The results indicated a significant correlation between high pretreatment NLR and poor PFS (HR=1.76, 95%CI:1.38-2.25, p<0.001) as well as poor OS (HR=2.61,95%CI:1.86-3.67, p<0.001). Subgroup analyses based on tumor stage revealed that the association between elevated NLR and poor PFS was only observed in advanced EC patients. Regarding PLR, an increased PLR was found to be indicative of inferior PFS (HR=1.44, 95%CI: 1.20-1.72, p<0.001) and OS (HR=1.72,95%CI:1.08-2.74, p=0.020). However, the sensitivity analyses suggested that the observed increase in PLR lack robustness in terms of its impact on inferior OS. Conclusion Elevated NLR and PLR are associated with inferior PFS and OS in EC patients receiving immunotherapy. These findings suggest that NLR and PLR levels hold promise as prognostic biomarkers in clinical practice, offering valuable guidance for personalized immunotherapy strategies. Systematic Review Registration PROSPERO https://www.crd.york.ac.uk/prospero/, identifier CRD42024596737.
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Affiliation(s)
| | | | | | | | | | - Lan Sun
- Department of Oncology, Bishan Hospital of Chongqing Medical University, Chongqing, China
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7
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Zhang X, Lian J, Chen F, Wang K, Xue H, Jia S, Wang W, Li Z, Liang H, Li H. Genomic, transcriptomic, and T cell receptor profiling in stratifying response to first-line chemoradiotherapy or radiotherapy for esophageal squamous cell carcinoma. Front Oncol 2025; 14:1495200. [PMID: 39834937 PMCID: PMC11743576 DOI: 10.3389/fonc.2024.1495200] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2024] [Accepted: 11/26/2024] [Indexed: 01/22/2025] Open
Abstract
Introduction Esophageal squamous cell carcinoma (ESCC) accounts for 80% of esophageal cancer (EC) worldwide. The molecular characteristics of locally advanced ESCC have been extensively studied. Methods In this study, we investigate the genomic and transcriptomic characteristics and try to provide the basic T-cell receptors (TCRs) dynamics and its genomic and transcriptome association during the radiochemotherapy of ESCC using multi-omics analysis. Results A total of 23 patients with pathologic diagnoses of locally advanced ESCC were enrolled. The median tumor mutational burden (TMB) of the 23 ESCC patients were 3.47 mutations/ Mb (mega-base). The TP53, RTK/RAS, and NOTCH pathways were concurrently prevalent in ESCC. Besides, some less prevalent pathways, including WNT and HIPPO pathways also exhibited superior frequencies in ESCC. Meantime, we found the immune-hot tumor had higher immune infiltration scores. The median TMB in the progression-free survival (PFS) low group was significantly higher than that in the PFS-high group. The chromosomal copy number variation (CNV) burden of the neutrophil-to-lymphocyte ratio (NLR)-high group appeared to be higher than that of the NLR-low group, and the StromalScore in the NLR-low group was significantly higher. Clonality score was significantly increased from pre-treat to post-treat and from on-treat to post-treat. Shannon index was significantly decreased from pre-treat to post-treat and from on-treat to posttreat. Richness was significantly decreased from pre-treat to post-treat. Discussion Multiomics analysis provided the basic TCRs dynamics and their genomic and transcriptome association during the radio-chemotherapy of 23 locally advanced ESCC in China, and provided a valuable insights into the heterogeneity and the tumor microenvironment and treatment responses. Meantimes, the identification of biomarkers and the exploration of their association with treatment outcomes could have important implications for clinical practice.
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Affiliation(s)
- Xiaqin Zhang
- Department of Radiotherapy, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, Shanxi, China
| | - Jianhong Lian
- Department of Thoracic Surgery, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, Shanxi, China
| | | | - Kai Wang
- Geneplus-Beijing, Beijing, China
| | - Haoyuan Xue
- Shanxi Medical University, Taiyuan, Shanxi, China
| | - Sufang Jia
- Department of Radiotherapy, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, Shanxi, China
| | - Weili Wang
- Department of Radiotherapy, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, Shanxi, China
| | | | - Hua Liang
- Ludwig Center for Metastasis Research, Department of Radiation and Cellular Oncology, University of Chicago, Chicago, IL, United States
| | - Hongwei Li
- Department of Radiotherapy, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, Shanxi, China
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Fang R, Chen Y, Huang B, Wang Z, Zhu X, Liu D, Sun W, Chen L, Zhang M, Lyu K, Lei W. Predicting response to PD-1 inhibitors in head and neck squamous cell carcinomas using peripheral blood inflammatory markers. Transl Oncol 2025; 51:102222. [PMID: 39616985 DOI: 10.1016/j.tranon.2024.102222] [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: 07/14/2024] [Revised: 11/15/2024] [Accepted: 11/23/2024] [Indexed: 12/11/2024] Open
Abstract
Immune checkpoint inhibitor (ICI) treatment has the potential to induce durable disease remission. However, the current combined positive score (CPS) is insufficient accurate for predicting which patients will benefit from it. In the present study, a real-world retrospective study was conducted on 56 patients of HNSCC who received ICI treatment. Then the treatment that patient received and levels of pre-treatment blood inflammatory markers (NLR, MLR and PLR) were identified to develop a model for predicting immunotherapy response. Notably, the model achieved an area under the curve (AUC) of 0.877 (95 % CI 0.769-0.985) , providing a larger net benefit than the CPS marker (AUC=0.614, 95 % CI 0.466-0.762). Furthermore, the internal validation of the prediction model showed a C-index of 0.835. Patients with high score of the model would get improved PFS than those with low score. Therefore, the prediction model for patients with local advanced or R/M HNSCC receiving ICI treatment, which represented an better efficient prediction of immunotherapy response than CPS marker.
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Affiliation(s)
- Ruihua Fang
- Department of Otorhinolaryngology Head and Neck Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, Guangdong, PR China
| | - Yi Chen
- Department of Otorhinolaryngology Head and Neck Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, Guangdong, PR China
| | - Bixue Huang
- Department of Otorhinolaryngology Head and Neck Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, Guangdong, PR China
| | - Zhangfeng Wang
- Department of Otorhinolaryngology Head and Neck Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, Guangdong, PR China
| | - Xiaolin Zhu
- Department of Otorhinolaryngology Head and Neck Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, Guangdong, PR China
| | - Dawei Liu
- Department of Pathology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, Guangdong, PR China
| | - Wei Sun
- Department of Otorhinolaryngology Head and Neck Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, Guangdong, PR China
| | - Lin Chen
- Department of Otorhinolaryngology Head and Neck Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, Guangdong, PR China
| | - Minjuan Zhang
- Department of Otorhinolaryngology Head and Neck Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, Guangdong, PR China
| | - Kexing Lyu
- Department of Otorhinolaryngology Head and Neck Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, Guangdong, PR China.
| | - Wenbin Lei
- Department of Otorhinolaryngology Head and Neck Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, Guangdong, PR China.
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Manne A, Tounkara F, Min E, Samuel P, Benson K, Noonan AM, Mittra A, Hays J, Roychowdhury S, Malalur P, Rahman S, Jin N, Pitter K, Miller E, Diaz A, He K. Risk Factors Predicting Outcomes in Advanced Upper Gastrointestinal Cancers Treated With Immune Checkpoint Inhibitors. Gastroenterology Res 2024; 17:195-204. [PMID: 39802925 PMCID: PMC11711034 DOI: 10.14740/gr1768] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2024] [Accepted: 09/07/2024] [Indexed: 01/16/2025] Open
Abstract
Background Immune checkpoint inhibitors (ICIs) have moved to the frontline in recent years to manage upper gastrointestinal (UGI) tumors, such as esophageal and gastric cancers. This retrospective review sheds light on real-world data on ICI-treated UGI tumors to identify risk factors (clinical and pathological) impacting the outcome other than traditional biomarkers (programmed cell death ligand 1 (PD-L1) or microsatellite instability status). Methods Patients with UGI tumors who received at least one dose of ICI for stage IV or recurrent disease between January 1, 2015, and July 31, 2021, at The Ohio State University were included in the study. The patients' baseline characteristics, labs, and blood counts (even at disease progression) were extracted with survival outcomes (progression-free survival (PFS) and overall survival (OS)). Descriptive statistics, log-rank test and Cox proportional hazard model for survival outcomes, Fisher exact test for categorical variables, were conducted using JMP Pro 16 (SAS Institute Inc., Cary, NC). Results We had 64 patients (84% males) included in the study, with the racial distribution as follows: 88% Caucasian, 5% African American, 1% Asian, and 6% from other racial groups. Men and the use of ICI in third lines or more had a positive impact on PFS and OS. For OS, 1) history of surgery positively impacted the outcome, while bone metastases worsened it; 2) baseline red blood cell count (RBC), hemoglobin, and thyroid-stimulating hormone (TSH) negatively impacted the OS. For PFS, 1) PD-L1 positivity, baseline lymphocyte count, and aspartate transferase levels had a positive impact; 2) human epidermal growth factor receptor 2 (HER2) positivity, baseline RBC, TSH, alkaline phosphatase, and alanine transferase (AST) levels had a negative impact. A slight increase in white blood cell (WBC) count (by 1.54, P = 0.02) and a drop in lymphocyte count (by 0.1907, P = 0.003) was significantly associated with disease progression. Conclusions Baseline risk factors and monitoring blood counts can help predict outcomes in ICI-treated UGI tumors. We need larger studies to confirm this.
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Affiliation(s)
- Ashish Manne
- Division of Medical Oncology, Department of Internal Medicine, The Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210, USA
| | - Fode Tounkara
- Department of Biostatistics, The Ohio State University, Columbus, OH 432120, USA
| | - Eric Min
- Division of Medical Oncology, Department of Internal Medicine, The Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210, USA
| | - Paul Samuel
- Division of Medical Oncology, Department of Internal Medicine, The Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210, USA
| | - Katherine Benson
- Division of Medical Oncology, Department of Internal Medicine, The Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210, USA
| | - Anne M. Noonan
- Division of Medical Oncology, Department of Internal Medicine, The Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210, USA
| | - Arjun Mittra
- Division of Medical Oncology, Department of Internal Medicine, The Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210, USA
| | - John Hays
- Division of Medical Oncology, Department of Internal Medicine, The Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210, USA
| | - Sameek Roychowdhury
- Division of Medical Oncology, Department of Internal Medicine, The Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210, USA
| | - Pannaga Malalur
- Division of Medical Oncology, Department of Internal Medicine, The Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210, USA
| | - Shafia Rahman
- Division of Medical Oncology, Department of Internal Medicine, The Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210, USA
| | - Ning Jin
- Division of Medical Oncology, Department of Internal Medicine, The Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210, USA
| | - Kenneth Pitter
- Department of Radiation Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210, USA
| | - Eric Miller
- Department of Radiation Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210, USA
| | - Alexandra Diaz
- Department of Radiation Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210, USA
| | - Kai He
- Division of Medical Oncology, Department of Internal Medicine, The Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210, USA
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10
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Han Y, Zheng S, Chen Y. Prognostic value of lymphocyte to monocyte ratio in patients with esophageal cancer: a systematic review and meta-analysis. Front Oncol 2024; 14:1401076. [PMID: 39659783 PMCID: PMC11628381 DOI: 10.3389/fonc.2024.1401076] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2024] [Accepted: 11/12/2024] [Indexed: 12/12/2024] Open
Abstract
Objectives To report the largest systematic review and meta-analysis to evaluate prognostic value of lymphocyte to monocyte ratio (LMR) in patients with esophageal cancer. Methods We conducted a systematic literature retrieval via PubMed, Embase, Web of Science, and Cochrane until December, 2023 for studies which evaluated the prognostic value of LMR in patients with esophageal cancer. Outcomes measured were overall survival (OS), disease-free survival (DFS), relapse-free survival (RFS), and progression-free survival (PFS). Results 11 studies including 3,377 patients with esophageal cancer were included for meta-analysis. Meta-analysis demonstrated that OS (HR: 1.65; 95% CI: 1.19, 2.31; P = 0.003) and DFS (HR: 1.48; 95% CI: 1.09, 2.01; P = 0.01) were significantly shorter in the low LMR group compared with the high LMR group. In addition, meta-analysis revealed a similar PFS (HR: 1.58; 95% CI: 1.00, 2.51; P = 0.05) and RFS (HR: 1.17; 95% CI: 0.93, 1.46; P = 0.18) in the two groups. Subgroup analysis found that the predictive value of LMR for OS remained significant in resectable and unresectable esophageal cancers, and in studies with follow-up ≥24 months and < 24 months. Subgroup analysis based on treatment methods found that the prognostic value of LMR was significant for both patients who received PD-1/PD-L1 inhibitors and those who did not receive PD-1/PD-L1 inhibitors. However, subgroup analysis based on LMR threshold found that the significance remained in studies with LMR threshold<3.5 (HR: 2.09; 95% CI: 1.13, 3.87; P = 0.02) but disappeared in studies with LMR threshold ≥ 3.5 (HR: 1.39; 95% CI: 0.93, 2.07; P = 0.11). Conclusions Low LMR is associated with poor prognosis in patients with esophageal cancer. Due to the simple availability and low cost of routine blood tests in clinical practice, LMR can be widely used to assess prognosis and construct risk prediction models for patients with esophageal cancer. Systematic review registration PROSPERO, identifier CRD42024509796.
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Affiliation(s)
- Yongqi Han
- Department of Oncology, The Fourth School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China
- Department of Oncology, Hangzhou First People’s Hospital, Hangzhou, China
- Department of Oncology, Hangzhou Cancer Hospital, Hangzhou, China
- Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Hangzhou First People’s Hospital, Hangzhou, China
| | - Song Zheng
- Department of Oncology, The Fourth School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China
- Department of Oncology, Hangzhou First People’s Hospital, Hangzhou, China
- Department of Oncology, Hangzhou Cancer Hospital, Hangzhou, China
- Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Hangzhou First People’s Hospital, Hangzhou, China
| | - Yijing Chen
- Department of Oncology, Hangzhou First People’s Hospital, Hangzhou, China
- Department of Oncology, Hangzhou Cancer Hospital, Hangzhou, China
- Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Hangzhou First People’s Hospital, Hangzhou, China
- Department of Oncology, Zhejiang University School of Medicine, Hangzhou, China
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11
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Shen L, Chen Z, Zhang Z, Wu Y, Ren Y, Li Y, Li Y, Yin X, Han F, Chen Y. Clinical Efficacy of Taxol Plus Platinum (TP) Chemotherapy Combined with Delayed Administration of PD-1 Inhibitors in Patients with Locally Advanced, Recurrent or Metastatic Esophageal Squamous Cell Carcinoma: A Retrospective Study. Drug Des Devel Ther 2024; 18:2761-2773. [PMID: 38979399 PMCID: PMC11230125 DOI: 10.2147/dddt.s455248] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2024] [Accepted: 06/19/2024] [Indexed: 07/10/2024] Open
Abstract
Purpose Immune checkpoint inhibitors (ICIs) combined with chemotherapy have become the first-line standard treatment for locally advanced or metastatic esophageal squamous cell carcinoma (ESCC). The evidence also demonstrates improved synergistic effects of chemotherapy when combined with delayed administration of ICIs. In this study, we conducted a retrospective investigation into the treatment efficacy of taxol plus platinum (TP) chemotherapy combined with delayed administration of PD-1 inhibitors for ESCC patients. Patients and Methods Clinical data of ESCC patients who received PD-1 inhibitors 3-5 days after TP chemotherapy as first-line treatment was retrospectively reviewed between January 2019 and April 2023. Clinical outcomes and treatment safety were analyzed. The potential roles of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and pan-immune-inflammation value (PIV) were investigated. Results A total of 34 locally advanced, recurrent or metastatic ESCC patients received PD-1 inhibitors 3-5 days following TP chemotherapy were included. The objective response rate (ORR) and disease control rate (DCR) were 85.3% and 97.1% respectively. The median progression-free survival (PFS) and overall survival (OS) were 13.2 and 19.1 month respectively. Seven patients received radical surgery, 1 patient achieved pathologic complete response (pCR) and 3 patients achieved major pathologic response (MPR). Among the 27 patients without surgery, the median PFS and OS were 9.7 and 19.1 month respectively. A more favorable prognosis was correlated with NLR less than 3 at the 3rd and 4th cycle of immunochemotherapy. No significant correlations between other parameters (PLR, MLR and PIV) and prognosis were observed. A total of 22 patients developed grade 3-4 toxicity events. Conclusion The optimized sequence of PD-1 inhibitors administered 3-5 days after TP chemotherapy as the first-line treatment of ESCC demonstrated favorable treatment efficacy. Pretreatment NLR of less than 3 at the 3rd and 4th cycle of immunochemotherapy is associated with a better prognosis.
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Affiliation(s)
- Lin Shen
- Department of Radio-Chemotherapy, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou City, Jiangsu Province, People's Republic of China
| | - Zixuan Chen
- Department of Radio-Chemotherapy, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou City, Jiangsu Province, People's Republic of China
| | - Zhi Zhang
- Department of Medical Oncology, Baoying Clinical College, Medical College of Yangzhou University, Yangzhou City, Jiangsu Province, People's Republic of China
| | - Yunjiang Wu
- Department of Thoracic Surgery, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou City, Jiangsu Province, People's Republic of China
| | - Yue Ren
- Department of Radio-Chemotherapy, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou City, Jiangsu Province, People's Republic of China
| | - Ying Li
- Department of Radio-Chemotherapy, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou City, Jiangsu Province, People's Republic of China
| | - Yue Li
- Department of Radio-Chemotherapy, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou City, Jiangsu Province, People's Republic of China
| | - Xudong Yin
- Department of Radio-Chemotherapy, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou City, Jiangsu Province, People's Republic of China
| | - Fang Han
- Department of Radio-Chemotherapy, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou City, Jiangsu Province, People's Republic of China
| | - Yong Chen
- Department of Radio-Chemotherapy, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou City, Jiangsu Province, People's Republic of China
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Yoshimura A, Nagahara A, Ishizuya Y, Yamamoto Y, Hatano K, Kawashima A, Nakai Y, Nakayama M, Nishimura K, Nonomura N, Kato T. The prognostic impact of peripheral blood eosinophil counts in metastatic renal cell carcinoma patients treated with nivolumab. Clin Exp Med 2024; 24:111. [PMID: 38780659 PMCID: PMC11116198 DOI: 10.1007/s10238-024-01370-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2024] [Accepted: 05/04/2024] [Indexed: 05/25/2024]
Abstract
Although immune checkpoint inhibitors (ICIs) have gained approval for metastatic renal cell carcinoma (mRCC), the response rate is still limited. Therefore, it is urgent to explore novel markers of responses to ICIs that can help assess clinical benefits. Recently, it has been noted that peripheral blood eosinophil counts are an independent factor correlated with clinical outcome of ICIs in some types of cancer. We investigated peripheral blood absolute eosinophil counts (AECs) at baseline and 4 weeks after the initiation of nivolumab for mRCC patients between February 2016 and May 2022. In addition, we examined clinicopathological features including irAEs and analyzed the correlation between AECs and clinical efficacy of nivolumab. The median progression-free survival (PFS) and overall survival (OS) for all patients were 5.7 and 25.5 months, respectively. The median AECs in patients with irAEs were significantly higher at baseline and 4 weeks after the treatment compared to those without irAEs (p < 0.001 and p = 0.001). With the cutoff value of AECs of 329 cells/µL at 4 weeks after the treatment for prediction of irAEs, high-AECs groups had significantly higher number of responders compared with that in low-AECs group (p < 0.001). Accordingly, the PFS and OS were significantly better in patients with high-AECs group than those in low-AECs group (p = 0.03 and p = 0.009). High-AECs at 4 weeks after the treatment serve as the prominent surrogate marker associated with the incidence of irAEs and better clinical outcome in mRCC patients receiving nivolumab.
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Affiliation(s)
- Akihiro Yoshimura
- Departments of Urology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Akira Nagahara
- Department of Urology, Osaka International Cancer Institute, Osaka, Japan
| | - Yu Ishizuya
- Departments of Urology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Yoshiyuki Yamamoto
- Departments of Urology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Koji Hatano
- Departments of Urology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Atsunari Kawashima
- Departments of Urology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Yasutomo Nakai
- Department of Urology, Osaka International Cancer Institute, Osaka, Japan
| | - Masashi Nakayama
- Department of Urology, Osaka International Cancer Institute, Osaka, Japan
| | - Kazuo Nishimura
- Department of Urology, Osaka International Cancer Institute, Osaka, Japan
| | - Norio Nonomura
- Departments of Urology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Taigo Kato
- Departments of Urology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
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Ma H, Jia J, Sun Z, Xiao X, Liang S, Zhao L, Zhang Z. The detection of PD-L1 expression on liquid-based cytology in pleural effusion of lung adenocarcinoma and its prognostic evaluation: Between paired liquid-based cytology and cell block samples. Diagn Cytopathol 2024; 52:235-242. [PMID: 38263766 DOI: 10.1002/dc.25276] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2023] [Revised: 01/02/2024] [Accepted: 01/08/2024] [Indexed: 01/25/2024]
Abstract
BACKGROUND Programmed death-ligand 1 (PD-L1) expression levels measured by immunohistochemistry have been proven to predict the outcome of immunotherapy in lung adenocarcinoma (LUAD). However, data on PD-L1 expression on liquid-based cytology (LBC) in malignant pleural effusion (MPE) is scarce. METHODS This study cohort included 60 cases with MPE suffering from LUAD. PD-L1 SP263 assay was used for immunocytochemistry (ICC) on LBC and matched cell block (CB) to validate ICC protocols on LBC slides. Clinical outcomes were analyzed based on immunotherapy and PD-L1 tumor proportion scores (TPS) on LBC slides and CBs. RESULTS PD-L1 expression with TPS ≥1% was lower in LBCs than in CBs (33 of 60 [55.0%] vs. 35 of 60 [58.3%]; p = .687). Even with the TPS ≥50% threshold, PD-L1 expression was lower in LBCs (10 of 60 [16.7%] vs. 15 of 60 [25%]; p = .125). Epidermal growth factor receptor (EGFR) exon 20 mutation, tumor cell proportion, and pleural fluid neutrophil-to-lymphocyte ratio were related to PD-L1 expression on CBs (p = .013, p = 0.022, and p = .011), respectively. Patients with subsequent immune checkpoint inhibitor therapy remained a better prognostic in subgroups of PD-L1 positive expression on LBC slides (TPS ≥1%, p = .041). CONCLUSIONS LBC specimens had comparable performance to CBs in PD-L1 assessment and predicting treatment response to PD-L1-defined therapy.
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Affiliation(s)
- Haiyue Ma
- Cytopathology Section, Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jia Jia
- Cytopathology Section, Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zihan Sun
- Cytopathology Section, Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xiaoyue Xiao
- Cytopathology Section, Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Shuo Liang
- Cytopathology Section, Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Linlin Zhao
- Cytopathology Section, Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zhihui Zhang
- Cytopathology Section, Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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14
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Shang H, Chen Y, Wang Q, Yang Y, Zhang J. A Correlation Evaluation Between the Peripheral Blood Index and the Prognosis of Advanced Esophageal Squamous Cell Carcinoma Patients Treated with Camrelizumab. J Inflamm Res 2024; 17:2009-2021. [PMID: 38566981 PMCID: PMC10986412 DOI: 10.2147/jir.s450669] [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] [Received: 11/19/2023] [Accepted: 03/20/2024] [Indexed: 04/04/2024] Open
Abstract
Purpose This study aimed to investigate the relationship between peripheral blood indices and the efficacy and prognosis of advanced esophageal squamous cell carcinoma (ESCC) patients treated with camrelizumab. Patients and Methods We retrospectively analyzed 64 patients who received camrelizumab for advanced ESCC at the Second People's Hospital of Lianyungang City between July 2020 and June 2022. The study included examination of the neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR), the systemic inflammation index (SII), the lymph-to-monocytes ratio (LMR), the absolute lymphocyte count (ALC), and lactate dehydrogenase (LDH). We used multivariate logistic regression analysis to explore the link existing between peripheral blood and the efficacy of treatment. Determination of potential prognostic factors for Progression-free survival (PFS) and Overall survival (OS) using Cox regression analysis. The nomogram model was developed based on the results of the Cox multivariate analysis. Patients were divided into three groups according to the reduction in LDH and LDL levels before treatment, and the Kaplan-Meier survival curves for the three groups were compared and ROC curves for LDH combined with PLR were plotted. Results Lower LDH (OR=6.237, 95% CI: 1.625-23.944) were independently associated with disease control rates(DCR). LDH was independently correlated with PFS (HR: 0.227 95% CI: 0.099-0.517). LDH and PLR were independently linked to OS. The C index of the nomogram model is 0.819, indicating good predictive performance. Kaplan-Meier Survival Curve suggested better OS in patients with reduced pretreatment LDH and PLR. The area under the ROC curve showed that the LDH index combined with the PLR index predicts patient survival better than the index alone. Conclusion LDH combined with PLR predicted prognosis in patients with ESCC treated with camrelizumab.
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Affiliation(s)
- Haotian Shang
- Department of Oncology, Clinical College of Second People’s Hospital of Lianyungang, Bengbu Medical College, Lianyungang, People’s Republic of China
| | - Yanan Chen
- Department of Oncology, Clinical College of Second People’s Hospital of Lianyungang, Bengbu Medical College, Lianyungang, People’s Republic of China
| | - Qiulu Wang
- Department of Oncology, Clinical College of Second People’s Hospital of Lianyungang, Bengbu Medical College, Lianyungang, People’s Republic of China
| | - Yongliang Yang
- Department of Oncology, Clinical College of Second People’s Hospital of Lianyungang, Bengbu Medical College, Lianyungang, People’s Republic of China
| | - Jingyu Zhang
- Department of Oncology, Clinical College of Second People’s Hospital of Lianyungang, Bengbu Medical College, Lianyungang, People’s Republic of China
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15
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Iwasa YI, Kitoh R, Yokota Y, Hori K, Kasuga M, Kobayashi T, Kanda S, Takumi Y. Post-treatment Neutrophil/Lymphocyte Ratio Is a Prognostic Factor in Head and Neck Cancers Treated With Nivolumab. CANCER DIAGNOSIS & PROGNOSIS 2024; 4:182-188. [PMID: 38434918 PMCID: PMC10905290 DOI: 10.21873/cdp.10305] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 11/28/2023] [Accepted: 01/05/2024] [Indexed: 03/05/2024]
Abstract
Background/Aim Inflammation and nutrition-based biomarkers, such as the neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), lymphocyte/monocyte ratio (LMR), C-reactive protein/albumin ratio (CAR), prognostic nutritional index (PNI), systemic immune inflammation index (SII), and systemic inflammation response index (SIRI), have prognostic value for several types of malignancies. Markers that precisely reflect the prognosis of patients with head and neck cancers (HNCs) treated with immune-checkpoint inhibitors remain unclear. This retrospective study aimed to investigate the prognostic value of hematological markers before and after treatment with nivolumab in patients with recurrent or metastatic HNC (RM-HNC). Patients and Methods We evaluated the clinical data of 44 patients with recurrent/metastatic head and neck squamous cell carcinoma treated with nivolumab between April 2017 and April 2023 at Shinshu University Hospital. Values of hematological biomarkers (NLR, LMR, PLR, CAR, PNI, SII, and SIRI) were calculated before and 4-6 weeks after nivolumab initiation. Receiver operating characteristic curves were constructed to determine the cutoff values of pre- and post-treatment markers for overall survival (OS) and progression-free survival (PFS). Results Among all pre- and post-treatment markers, post-treatment NLR showed the highest area under the curve (AUC=0.702). A high post-treatment NLR (cutoff value, 4.01) was associated with a poor OS (p=0.027) and a tendency for shorter PFS (p=0.117). Multivariate analysis showed that a high post-treatment NLR was significantly associated with poor OS (p=0.026). Conclusion A high post-treatment NLR was associated with poor response to nivolumab in head and neck cancers.
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Affiliation(s)
- Yoh-Ichiro Iwasa
- Department of Otorhinolaryngology-Head and Neck Surgery, Shinshu University School of Medicine, Matsumoto, Japan
| | - Ryosuke Kitoh
- Department of Otorhinolaryngology-Head and Neck Surgery, Shinshu University School of Medicine, Matsumoto, Japan
| | - Yoh Yokota
- Department of Otorhinolaryngology-Head and Neck Surgery, Shinshu University School of Medicine, Matsumoto, Japan
| | - Kentaro Hori
- Department of Otorhinolaryngology-Head and Neck Surgery, Shinshu University School of Medicine, Matsumoto, Japan
| | - Mariko Kasuga
- Department of Otorhinolaryngology-Head and Neck Surgery, Shinshu University School of Medicine, Matsumoto, Japan
| | - Takashi Kobayashi
- Department of Hematology and Medical Oncology, Shinshu University School of Medicine, Matsumoto, Japan
| | - Shintaro Kanda
- Department of Hematology and Medical Oncology, Shinshu University School of Medicine, Matsumoto, Japan
| | - Yutaka Takumi
- Department of Otorhinolaryngology-Head and Neck Surgery, Shinshu University School of Medicine, Matsumoto, Japan
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Cao J, Chen Q, Bai X, Liu L, Ma W, Lin C, Lu F, Zhou T, Zhan J, Huang Y, Yang Y, Luo F, Zhao H. Predictive value of immunotherapy-induced inflammation indexes: dynamic changes in patients with nasopharyngeal carcinoma receiving immune checkpoint inhibitors. Ann Med 2023; 55:2280002. [PMID: 38065623 PMCID: PMC10836292 DOI: 10.1080/07853890.2023.2280002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2023] [Accepted: 10/31/2023] [Indexed: 12/18/2023] Open
Abstract
BACKGROUND Immune checkpoint inhibitors (ICIs) have achieved substantial advancements in clinical care. However, there is no strong evidence for identified biomarkers of ICIs in NPC. METHODS In this retrospective study, 284 patients were enrolled into a training or validation cohort. Inflammatory indexes based on peripheral blood parameters were evaluated, including the systemic immune-inflammation index (SII), the neutrophil-lymphocyte ratio (NLR), the platelet-lymphocyte ratio (PLR), the lymphocyte-to-C-reactive protein ratio (LCR), and the lymphocyte-monocyte ratio (LMR). The optimum cut-off value for patient stratification was identified using X-tile. The Kaplan-Meier method and Cox's proportional regression analyses were used to identify prognostic factors. RESULTS Immunotherapy significantly changed the levels of SII, NLR, PLR, LCR and LMR in NPC patients. Patients with lower SII, NLR, and PLR, as well as those with higher LCR and LMR, before immunotherapy had superior PFS (all p < 0.05). Moreover, PFS in the decreased SII, reduced NLR and increased LMR group was significantly longer than in the opposite group (all p < 0.05). Both univariate and multivariate analyses validated that baseline SII and LMR, and the immunotherapy-related SII reduction and LMR elevation were independent prognostic factors for PFS in advanced NPC patients receiving ICIs. CONCLUSIONS Immune checkpoint inhibitor treatments significantly changed the levels of SII, NLR, PLR, LCR and LMR in NPC patients treated with immunotherapy. A lower baseline SII and a higher baseline LMR, and a reduction in SII and an elevation in LMR after immunotherapy are favorable factors for predicting survival among advanced NPC patients.
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Affiliation(s)
- Jiaxin Cao
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China
| | - Qun Chen
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China
| | - Xue Bai
- The Second Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, China
| | - Lusha Liu
- The Second Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, China
| | - Wenjuan Ma
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China
| | - Chaozhuo Lin
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China
| | - Feiteng Lu
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China
| | - Ting Zhou
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China
| | - Jianhua Zhan
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China
| | - Yan Huang
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China
| | - Yunpeng Yang
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China
| | - Fan Luo
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China
| | - Hongyun Zhao
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China
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17
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Wang Y, Ni Q. Prognostic and clinicopathological significance of Systemic Immune-Inflammation Index in cancer patients receiving immune checkpoint inhibitors: a meta-analysis. Ann Med 2023; 55:808-819. [PMID: 36892953 PMCID: PMC10795596 DOI: 10.1080/07853890.2023.2181983] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2022] [Accepted: 02/13/2023] [Indexed: 03/10/2023] Open
Abstract
BACKGROUND Among malignant neoplasm patients taking immune checkpoint inhibitors (ICIs), it remains unknown how the systemic immune-inflammation index (SII) affects their clinical prognosis. We therefore performed the present meta-analysis by collecting the most recent data, so that SII's prognostic value among ICI-receiving carcinoma patients could be fully clarified. METHODS For the prognostic significance evaluation of SII in ICI-receiving carcinoma patients, the combined hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated. RESULTS The number of studies enrolled in the present meta-analysis totaled 17, where 1,990 patients were involved. Among the ICI-treated carcinoma patients, a high SII was linked significantly to inferior overall survival (OS) (HR = 2.62, 95% CI = 1.76-3.90), as well as progression-free survival (PFS) (HR = 2.09, 95% CI = 1.48-2.95) (p both <.001). Contrastively, SII was linked insignificantly to the age (OR = 1.08, 95% CI = 0.39-2.98, p = .881), gender (OR = 1.01, 95% CI = 0.59-1.73, p = .959), lymph node (LN) metastasis (OR = 1.41, 95% CI = 0.92-2.17, p = .117), or metastatic site quantity (OR = 1.49, 95% CI = 0.90-2.46, p = .119). CONCLUSION There are prominent associations of elevated SII with the poor survival outcomes (both short- and long-terms) among the ICIreceiving carcinoma patients. SII has potential as a reliable and cheap prognostic biomarker in the clinic for carcinoma patients receiving ICIs.
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Affiliation(s)
- Yan Wang
- Clinical Laboratory, Huzhou Central Hospital, Affiliated Central Hospital of Huzhou University, Huzhou, Zhejiang, China
| | - Qunqin Ni
- Clinical Laboratory, Traditional Chinese Medical Hospital of Huzhou Affiliated to Zhejiang Chinese Medical University, Huzhou, Zhejiang, China
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Wang HC, Huang X, Chen J, Li Y, Cong Y, Qu BL, Feng SQ, Liu F. Long-term efficacy and predictors of pembrolizumab-based regimens in patients with advanced esophageal cancer in the real world. World J Gastroenterol 2023; 29:5641-5656. [PMID: 38077159 PMCID: PMC10701330 DOI: 10.3748/wjg.v29.i41.5641] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2023] [Revised: 10/07/2023] [Accepted: 10/23/2023] [Indexed: 11/07/2023] Open
Abstract
BACKGROUND Pembrolizumab combined with chemotherapy has been proven effective as first-line therapy in patients with advanced esophageal cancer. Few trials have assessed the safety and efficacy of this treatment in patients with locally advanced disease. AIM To analyze long-term outcomes of pembrolizumab in locally advanced or metastatic esophageal squamous cell carcinoma (ESCC) in the real world. METHODS Patients with advanced ESCC admitted to our center from October 2019 to October 2021 were enrolled in this study. Clinical staging of the patients was based on the 8th edition of the American Joint Committee on Cancer TNM staging system. The patients received different treatments based on clinical stage. In brief, patients with locally advanced and resectable ESCC received neoadjuvant therapy combined with surgery. For those who were not candidates for resection, radical concurrent chemoradiotherapy plus pembrolizumab was more preferable. Patients with metastatic ESCC or who were unsuitable for radiotherapy underwent chemotherapy in combination with pembrolizumab. Long-term survival outcomes such as overall survival (OS), progression-free survival, disease-free survival, long-term adverse effects (AEs), immune maintenance therapy and predictors of immune checkpoint inhibitors (ICIs) efficacy were evaluated. RESULTS A total of 55 patients with advanced ESCC were enrolled in this retrospective, observational study. The median age was 61 years (range 44-74), with 47.3% (26/55) of the patients in stage IV and 45.5% of the patients had the tumor (25/55) located in the middle third of the esophagus. The median OS in all patients was not reached. The 12-mo OS rate among all patients was 78.8% and the 18-mo OS rate was 72.7%. 9 patients died due to tumor progression and 7 patients died due to treatment-related complications. The therapeutic effect evaluated at the interim evaluation was significantly reflected in the long-term outcome. Patients with complete response or partial response in all patients (P = 0.005) and in the chemoradiotherapy plus pembrolizumab group (P = 0.007) obtained a better prognosis than non-responders. A total of 20 patients (20/55, 36%) received immune maintenance therapy. Baseline peripheral blood biomarkers of the neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and neutrophil-to-(leukocyte-neutrophil) ratio did not predict the efficacy of ICIs. CONCLUSION Pembrolizumab combined with chemotherapy or radiotherapy resulted in favorable long-term survival in patients with locally advanced or metastatic ESCC, with safe and manageable long-term AEs.
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Affiliation(s)
- Hong-Chi Wang
- Department of Radiotherapy, The First Medical Center of Chinese PLA General Hospital, Beijing 100853, China
| | - Xiang Huang
- Department of Radiotherapy, The First Medical Center of Chinese PLA General Hospital, Beijing 100853, China
| | - Jing Chen
- Department of Radiotherapy, The First Medical Center of Chinese PLA General Hospital, Beijing 100853, China
| | - Ye Li
- Department of Radiotherapy, The First Medical Center of Chinese PLA General Hospital, Beijing 100853, China
| | - Yang Cong
- Department of Radiotherapy, The First Medical Center of Chinese PLA General Hospital, Beijing 100853, China
| | - Bao-Lin Qu
- Department of Radiotherapy, The First Medical Center of Chinese PLA General Hospital, Beijing 100853, China
| | - Sheng-Qiang Feng
- Health Service, The Guard Bureau of Joint Staff Department of Chinese PLA, Beijing 100017, China
| | - Fang Liu
- Department of Radiotherapy, The First Medical Center of Chinese PLA General Hospital, Beijing 100853, China
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Yang Q, Huang H, Zhang G, Weng N, Ou Z, Sun M, Luo H, Zhou X, Gao Y, Wu X. Contrast-enhanced CT-based radiomic analysis for determining the response to anti-programmed death-1 therapy in esophageal squamous cell carcinoma patients: A pilot study. Thorac Cancer 2023; 14:3266-3274. [PMID: 37743537 PMCID: PMC10665784 DOI: 10.1111/1759-7714.15117] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2023] [Revised: 09/06/2023] [Accepted: 09/07/2023] [Indexed: 09/26/2023] Open
Abstract
BACKGROUND In view of the fact that radiomics features have been reported as predictors of immunotherapy to various cancers, this study aimed to develop a prediction model to determine the response to anti-programmed death-1 (anti-PD-1) therapy in esophageal squamous cell carcinoma (ESCC) patients from contrast-enhanced CT (CECT) radiomics features. METHODS Radiomic analysis of images was performed retrospectively for image samples before and after anti-PD-1 treatment, and efficacy analysis was performed for the results of two different time node evaluations. A total of 68 image samples were included in this study. Quantitative radiomic features were extracted from the images, and the least absolute shrinkage and selection operator method was applied to select radiomic features. After obtaining selected features, three classification models were used to establish a radiomics model to predict the ESCC status and efficacy of therapy. A cross-validation strategy utilizing three folds was employed to train and test the model. Performance evaluation of the model was done using the area under the curve (AUC) of receiver operating characteristic, sensitivity, specificity, and precision metric. RESULTS Wavelet and area of gray level change (log-sigma) were the most significant radiomic features for predicting therapy efficacy. Fifteen radiomic features from the whole tumor and peritumoral regions were selected and comprised of the fusion radiomics score. A radiomics classification was developed with AUC of 0.82 and 0.884 in the before and after-therapy cohorts, respectively. CONCLUSIONS The combined model incorporating radiomic features and clinical CECT predictors helps to predict the response to anti-PD-1therapy in patients with ESCC.
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Affiliation(s)
- Qinzhu Yang
- School of Biomedical EngineeringShenzhen University Medical School, Shenzhen UniversityShenzhenChina
| | - Haofan Huang
- School of Biomedical EngineeringShenzhen University Medical School, Shenzhen UniversityShenzhenChina
- Department of Biomedical EngineeringHong Kong Polytechnic UniversityHong Kong SARChina
| | - Guizhi Zhang
- Department of RadiologyThe Eighth Affiliated Hospital of Sun Yat‐sen UniversityShenzhenChina
| | - Nuoqing Weng
- Department of Gastrointestinal Surgery, The Eighth Affiliated HospitalSun Yat‐sen UniversityShenzhenChina
| | - Zhenkai Ou
- School of Biomedical EngineeringShenzhen University Medical School, Shenzhen UniversityShenzhenChina
| | - Meili Sun
- Department of RadiologySun Yat‐sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer MedicineGuangzhouChina
| | - Huixing Luo
- Department of Gastrointestinal Surgery, The Eighth Affiliated HospitalSun Yat‐sen UniversityShenzhenChina
| | - Xuhui Zhou
- Department of RadiologyThe Eighth Affiliated Hospital of Sun Yat‐sen UniversityShenzhenChina
| | - Yi Gao
- School of Biomedical EngineeringShenzhen University Medical School, Shenzhen UniversityShenzhenChina
- Shenzhen Key Laboratory of Precision Medicine for Hematological MalignanciesShenzhenChina
- Marshall Laboratory of Biomedical EngineeringShenzhenChina
| | - Xiaobin Wu
- Department of Gastrointestinal Surgery, The Eighth Affiliated HospitalSun Yat‐sen UniversityShenzhenChina
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20
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Chen N, Xu X, Fan Y. Immune checkpoint inhibitors in the treatment of oesophageal squamous cell carcinoma: where are we and where are we going? Ther Adv Med Oncol 2023; 15:17588359231189420. [PMID: 37547447 PMCID: PMC10399266 DOI: 10.1177/17588359231189420] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2023] [Accepted: 07/05/2023] [Indexed: 08/08/2023] Open
Abstract
Oesophageal squamous cell carcinoma (ESCC) is a kind of malignant tumour with high invasiveness and a poor prognosis. Immunotherapy, especially immune checkpoint inhibitors (ICIs), is a rapidly growing therapeutic method that activates and enhances anti-tumour immunity to treat patients with malignancy. Several clinical trials have confirmed the efficacy of ICIs in the treatment of ESCC. ICIs have been approved for the treatment of patients with ESCC. However, only a subset of patients can obtain excellent benefits from ICI therapy. In recent years, there has been a growing interest in exploring predictive biomarkers of immunotherapy response. In this review, we highlighted the predictive biomarkers for the prognosis of ESCC patients treated with ICIs and pointed out the existing problems and the direction of future research in this field.
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Affiliation(s)
- Ning Chen
- Department of Oncology, The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
- Department of Medical Thoracic Oncology, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine, Chinese Academy of Sciences, Hangzhou, Zhejiang, China
| | - Xiaoling Xu
- Department of Medical Thoracic Oncology, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine, Chinese Academy of Sciences, No. 1 East Banshan Road, Gongshu District, Hangzhou, Zhejiang 310022, China
| | - Yun Fan
- Department of Medical Thoracic Oncology, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine, Chinese Academy of Sciences, No. 1 East Banshan Road, Gongshu District, Hangzhou, Zhejiang 310022, China
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21
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Qi W, Wang X, Li C, Li S, Li H, Xu F, Chen J, Zhao S, Li H. Pretreatment absolute lymphocyte count is an independent predictor for survival outcomes for esophageal squamous cell carcinoma patients treated with neoadjuvant chemoradiotherapy and pembrolizumab: An analysis from a prospective cohort. Thorac Cancer 2023; 14:1556-1566. [PMID: 37089116 PMCID: PMC10260499 DOI: 10.1111/1759-7714.14898] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2023] [Revised: 03/30/2023] [Accepted: 04/02/2023] [Indexed: 04/25/2023] Open
Abstract
BACKGROUND The aim of the study was to analyze the relationship between pretreatment inflammatory biomarkers (IBs) and survival outcomes for patients with esophageal squamous cell carcinoma (ESCC) treated with neoadjuvant chemoradiotherapy (neo-CRT) and pembrolizumab. METHODS Clinical variables and IBs (absolute monocyte count [AMC], absolute lymphocyte count [ALC], platelet count [PLT], neutrophil-to-lymphocyte ratio [NLR], platelet-to-lymphocyte ratio [PLR], lymphocyte-to-monocyte ratio [LMR], pan-immune inflammation value [PIV], systemic immunoinflammatory index [SII], systemic immunoreactivity index [SIRI] and prognostic nutritional index [PNI]) were collected. Univariate and multivariate analysis were performed to identify the independent factors for outcomes of ESCC. RESULTS A total of 51 patients were included. Of these, 35 patients achieved pathological complete response (pCR) after neo-CRT and pembrolizumab (pCR: 68.6%). With a median follow-up of 20 months, the two-year PFS and OS of the cohort was 64% and 91%, respectively. Multivariate logistic regression analysis indicated that ALC (overall response [OR] 4.4, p = 0.051) and PLT (OR 6.7, p = 0.023) were two independent predictors for achieving pCR among ESCC treated with neo-CRT and pembrolizumab. Multivariate Cox regression analysis showed that ALC (HR 0.27, p = 0.028) and SIRI (HR 3.13, p = 0.048) were two independent predictors associated with PFS. Kaplan Meier analysis demonstrated that the PFS of ESCC with high baseline ALC was significantly better than those with low ALC (2-year PFS: 77% vs. 47%, p = 0.027), but not for overall survival (2-year OS: 96% vs. 87%, p = 0.46). CONCLUSIONS This retrospective analysis based on a prospective cohort for the first time demonstrates that pretreatment ALC is an independent predictor for achieving pCR and favorable outcomes of ESCC treated with neo-CRT and pembrolizumab.
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Affiliation(s)
- Wei‐Xiang Qi
- Department of Radiation Oncology, Ruijin HospitalShanghai Jiaotong University School of MedicineShanghaiChina
| | - Xiaoyan Wang
- Department of Radiation OncologyThe Third Affiliated Hospital of Wenzhou Medical UniversityWenzhouChina
| | - Chengqiang Li
- Department of Thoracic Surgery, Ruijin HospitalShanghai Jiaotong University School of MedicineShanghaiChina
| | - Shuyan Li
- Department of Radiation Oncology, Ruijin HospitalShanghai Jiaotong University School of MedicineShanghaiChina
| | - Huan Li
- Department of Radiation Oncology, Ruijin HospitalShanghai Jiaotong University School of MedicineShanghaiChina
| | - Feifei Xu
- Department of Radiation Oncology, Ruijin HospitalShanghai Jiaotong University School of MedicineShanghaiChina
| | - Jiayi Chen
- Department of Radiation Oncology, Ruijin HospitalShanghai Jiaotong University School of MedicineShanghaiChina
| | - Shengguang Zhao
- Department of Radiation Oncology, Ruijin HospitalShanghai Jiaotong University School of MedicineShanghaiChina
| | - Hecheng Li
- Department of Radiation OncologyThe Third Affiliated Hospital of Wenzhou Medical UniversityWenzhouChina
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Zhang Z, Yang L, Wang D, Ruan Y, Zhang J, Zhao L, Yang L, Lou C. Retrospective study of the combination of TP and PF regimens with or without immune checkpoint inhibitors for the first-line treatment of locally advanced or advanced esophageal squamous cell carcinoma. Ther Adv Med Oncol 2023; 15:17588359231169981. [PMID: 37188111 PMCID: PMC10176547 DOI: 10.1177/17588359231169981] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2022] [Accepted: 03/28/2023] [Indexed: 05/17/2023] Open
Abstract
Objective To investigate the efficacy and safety differences between the cisplatin + paclitaxel (TP) and cisplatin + fluorouracil (PF) regimens in combination with or without immune checkpoint inhibitors (ICIs) in advanced esophageal squamous cell carcinoma (ESCC) first-line treatment and prognostic factors. Methods We selected the medical records of patients with late stage ESCC admitted to the hospital between 2019 and 2021. Based on the first-line treatment regimen, control groups were divided into chemotherapy plus ICIs (n = 243) and non-ICIs (n = 171), 119 (49%) in the TP + ICIs group, 124 (51%) in the PF + ICIs group, 83 (48.5%) in the TP group, and 88 (51.5%) in the PF group in the control group. We analyzed and compared factors related to efficacy, safety, or response to toxicity and prognosis across four subgroups. Results The overall objective response rate (ORR) and disease control rate (DCR) of the TP plus ICIs group were 42.1% (50/119) and 97.5% (116/119), respectively, which were 6.6% and 7.2% higher than those of the PF plus ICIs group. Patients in the TP combined with ICIs group had higher overall survival (OS) and progression-free survival (PFS) than those in the PF combined with ICIs group [hazard ratio (HR) = 1.702, 95% confidence interval (CI): 0.767-1.499, p = 0.0167 and HR = 1.158, 95% CI: 0.828-1.619, p = 0.0055] ORR and DCR were 15.7% (13/83) and 85.5% (71/83) in the TP chemotherapy alone group, significantly higher than the PF group [13.6% (12/88) and 72.2% (64/88)] (p < 0.05), OS and PFS were also better in patients treated with TP regimen chemotherapy than PF (HR = 1.173, 95% CI: 0.748-1.839, p = 0.0014 and HR = 0.1.245, 95% CI: 0.711-2.183, p = 0.0061). Furthermore, following the combination of TP and PF diets with ICIs, the OS of the patients was higher than that of the group treated with chemotherapy alone (HR = 0.526, 95% CI: 0.348-0.796, p = 0.0023 and HR = 0.781, 95% CI: 0.0.491-1.244, p < 0.001). Regression analysis showed that the neutrophil-to-lymphocyte ratio (NLR), the control nuclear status score (CONUT), and the systematic immune inflammation index (SII) were independent prognostic factors for the efficacy of immunotherapy (p < 0.05). The overall incidence of treatment-associated adverse events (TRAEs) was 79.4% (193/243) and 60.8% (104/171) in the experimental and control groups, respectively, and there was no statistically significant difference in TRAEs between TP + ICIs (80.6%) and PF + ICIs (78.2%) (61.4%) and PF groups (60.2%) (p > 0.05). Overall, 21.0% (51/243) of patients in the experimental group experienced immune-related adverse events (irAEs), and all of these adverse effects were tolerated or remitted following drug treatment without affecting follow-up. Conclusion The TP regimen was associated with better PFS and OS with or without ICIs. Furthermore, high CONUT scores, high NLR ratios, and high SII were found to be associated with poor prognosis in combination immunotherapy.
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Affiliation(s)
| | - Lei Yang
- Harbin Medical University Cancer, Harbin,
China
| | - Dazhen Wang
- Harbin Medical University Cancer, Harbin,
China
| | - Yuli Ruan
- Harbin Medical University Cancer, Harbin,
China
| | | | - Lu Zhao
- Harbin Medical University Cancer, Harbin,
China
| | - Liu Yang
- Harbin Medical University Cancer, Harbin,
China
| | - Changjie Lou
- Department of Gastroenterology, Harbin Medical
University Cancer Hospital, 150 Haping Road, Nangang District, Harbin,
Heilongjiang 150081, China
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23
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Da L, Qu Z, Zhang C, Shen Y, Huang W, Zhang Y, Gu K. Prognostic value of inflammatory markers and clinical features for survival in advanced or metastatic esophageal squamous cell carcinoma patients receiving anti-programmed death 1 treatment. Front Oncol 2023; 13:1144875. [PMID: 37035159 PMCID: PMC10076857 DOI: 10.3389/fonc.2023.1144875] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2023] [Accepted: 03/06/2023] [Indexed: 04/11/2023] Open
Abstract
Purpose This study aims to assess the prognostic value of inflammatory markers and clinical features in advanced or metastatic esophageal squamous cell carcinoma (ESCC) patients receiving anti-programmed death 1 (PD-1) treatment. Methods Based on receiver operating characteristic curve (ROC) analysis, Youden's indexes were applied to determine the cut-off values for inflammatory markers, including neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocye ratio (dNLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII). Wilcoxon test was conducted to evaluate the changes in above inflammatory markers. Kaplan-Meier method was utilized to estimate progression-free survival (PFS) and overall survival (OS), and the Log-rank test was used to compare the different survival between groups. Univariate and multivariate Cox regression analyses were performed to assess the prognostic value of inflammatory markers and clinical features. Results 162 advanced or metastatic ESCC patients receiving anti-PD-1 treatment were enrolled in this retrospective study. The cut-off values of NLR, dNLR, MLR, PLR, and SII were 4.748, 2.214, 0.309, 250.505, and 887.895, respectively. NLR, dNLR, PLR, and SII declined significantly among the partial response (PR) (P<0.001, P<0.001, P=0.036, P<0.001), objective response rate (ORR) (P<0.001, P<0.001, P=0.036, P<0.001), and disease control rate (DCR) (P<0.001, P<0.001, P=0.038, P<0.001) groups, respectively. Significant increases were found in NLR (P<0.001), dNLR (P<0.001), MLR (P=0.001), and SII (P=0.024) when anti-PD-1 treatment failed. Multivariate Cox regression analysis indicated that NLR (P<0.001, P=0.002), lymph node metastasis (P=0.013, P=0.001), Eastern Cooperative Oncology Group Performance Status (ECOG PS) (P=0.008, P=0.002), and treatment lines (P=0.037, P=0.048) were significant prognostic indicators of PFS and OS. Additionally, SII (P=0.016) was also significantly related to OS in ESCC patients. The risk score model showed that low risk patients prolonged PFS and OS than those with middle or high risk (P<0.001, P<0.001). Conclusion Inflammatory markers can reflect short-term outcomes of anti-PD-1 treatment for ESCC patients. NLR, lymph node metastases, ECOG PS, and treatment lines are significant prognostic indicators for PFS and OS. And the risk score model constructed based on the above factors has favourable prognostic predictive value.
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Affiliation(s)
| | | | | | | | | | - Yiyin Zhang
- *Correspondence: Yiyin Zhang, ; Kangsheng Gu,
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Tian BW, Yang YF, Yang CC, Yan LJ, Ding ZN, Liu H, Xue JS, Dong ZR, Chen ZQ, Hong JG, Wang DX, Han CL, Mao XC, Li T. Systemic immune-inflammation index predicts prognosis of cancer immunotherapy: systemic review and meta-analysis. Immunotherapy 2022; 14:1481-1496. [PMID: 36537255 DOI: 10.2217/imt-2022-0133] [Citation(s) in RCA: 59] [Impact Index Per Article: 19.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Objective: This meta-analysis was designed to explore the association between the systemic immune-inflammation index (SII) and the therapeutic effect of immune checkpoint inhibitors. Materials & methods: The authors retrieved relevant studies published before May 25, 2022. Hazard ratio (HR) with 95% CI was used to evaluate the relationship between SII and overall survival (OS) and progression-free survival (PFS). Results: 14 articles comprising 2721 patients were included in this study. The pooled results proved that high SII levels were closely related to poor prognosis in cancer patients receiving immune checkpoint inhibitors (OS HR = 2.40; 95% CI: 2.04-2.82; PFS HR = 1.57; 95% CI: 1.33-1.86) and that an SII value of 750 was appropriate as a cut-off value (OS HR = 2.20; 95% CI: 1.83-2.63; PFS HR = 1.54; 95% CI: 1.33-1.80). Conclusion: High SII levels (>750) may be an indicator of worse OS and PFS in cancer patients treated with immune checkpoint inhibitors.
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Affiliation(s)
- Bao-Wen Tian
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, 250012, People's Republic of China
| | - Ya-Fei Yang
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, 250012, People's Republic of China
| | - Chun-Cheng Yang
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, 250012, People's Republic of China
| | - Lun-Jie Yan
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, 250012, People's Republic of China
| | - Zi-Niu Ding
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, 250012, People's Republic of China
| | - Hui Liu
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, 250012, People's Republic of China
| | - Jun-Shuai Xue
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, 250012, People's Republic of China
| | - Zhao-Ru Dong
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, 250012, People's Republic of China
| | - Zhi-Qiang Chen
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, 250012, People's Republic of China
| | - Jian-Guo Hong
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, 250012, People's Republic of China
| | - Dong-Xu Wang
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, 250012, People's Republic of China
| | - Cheng-Long Han
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, 250012, People's Republic of China
| | - Xin-Cheng Mao
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, 250012, People's Republic of China
| | - Tao Li
- Department of Hepatobiliary Surgery, Second Hospital of Shandong University, Jinan, 250012, People's Republic of China
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Nomogram Based on Monocyte-to-Lymphocyte Ratio to Predict Survival of Unresectable Esophageal Squamous Cell Carcinoma Who Receive First-Line PD-1/PD-L1 Inhibitors Combined with Chemotherapy. Curr Oncol 2022; 29:8937-8954. [PMID: 36421355 PMCID: PMC9689525 DOI: 10.3390/curroncol29110702] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2022] [Revised: 11/10/2022] [Accepted: 11/17/2022] [Indexed: 11/22/2022] Open
Abstract
BACKGROUND Chemoimmunotherapy has become the first-line treatment for unresectable esophageal squamous cell carcinoma (ESCC). Still, reliable biomarkers to identify patients who could benefit from this combined therapy remain uncertain. This study focused on elucidating the predictive significance of the monocyte-to-lymphocyte ratio (MLR) and establishing the prognostic nomogram for unresectable ESCC treated with chemoimmunotherapy. METHODS Data of clinical features, peripheral blood parameters, and treatment records were collected in unresectable ESCC patients who received PD-1/PD-L1 inhibitors plus chemotherapy as the first-line treatment from September 2017 to August 2021. The nomogram based on MLR and clinical parameters for predicting the overall survival (OS) was developed and validated. RESULTS Out of 81 patients enrolled, patients with a lower MLR had significantly longer progression-free survival (PFS) and OS than patients with a higher pretreatment MLR (p = 0.0067; p = 0.00069). The OS nomogram integrating MLR, performance status (PS) score, and body mass index (BMI) achieved a C-index of 0.770 (95%CI 0.645-0.896). The area under the ROC curve (AUC) value of the nomogram predicting 12-, 18-, and 24-month OS rates were 0.855, 0.792, and 0.744, respectively, which were higher than the clinical TNM staging system or the MLR. Stratified by the nomogram-generated scores, three risk groups (low, moderate, and high) in survival curves manifested a distinct difference (p < 0.0001). CONCLUSION MLR emerged as an independent predictive factor for PFS and OS in treatment-naive unresectable ESCC patients treated with chemoimmunotherapy. The constructed nomogram of MLR and clinical parameters was a reliable model for prognostic estimation.
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Chang L, Cheng Q, Ma Y, Wu C, Zhang X, Ma Q, He L, Li Q, Tao J. Prognostic Effect of the Controlling Nutritional Status Score in Patients With Esophageal Cancer Treated With Immune Checkpoint Inhibitor. J Immunother 2022; 45:415-422. [PMID: 36006239 PMCID: PMC9528939 DOI: 10.1097/cji.0000000000000438] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2022] [Accepted: 07/05/2022] [Indexed: 12/20/2022]
Abstract
In recent years, a growing number of clinical studies have shown that immune checkpoint inhibitor (ICI) can increase the remission rate and improve the prognosis of patients with esophageal cancer. The Controlling Nutritional Status (CONUT) score is a novel nutritional indicator that can predict the prognosis of certain malignancies. We retrospectively analyzed the clinical data of 69 patients with advanced esophageal cancer treated with ICI and assessed the relationship between clinicopathological factors including CONUT score, systemic immune-inflammatory index (SII), and neutrophil-to-lymphocyte ratio and the prognosis. We found the CONUT score and SII, neutrophil-to-lymphocyte ratio were an independent prognostic factor for overall survival ( P <0.05). Furthermore, among patients treated with ICI, a high CONUT score was associated with a significantly worse progression-free survival (PFS) and overall survival compared with a low CONUT group. In conclusion, the CONUT can be used to predict the efficacy and prognosis of ICI therapy in patients with esophageal cancer. Our studies have shown that the CONUT score can be used as an effective indicator for the prognosis of patients with esophageal cancer receiving ICI.
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Affiliation(s)
- Lele Chang
- Departments of Gastrointestinal Medical Oncology
| | - Qian Cheng
- Departments of Gastrointestinal Medical Oncology
| | - Yue Ma
- Departments of Gastrointestinal Medical Oncology
| | | | - Xuemei Zhang
- Thoracic Radiotherapy, Harbin Medical University Cancer Hospital, Harbin, China
| | - Qian Ma
- Departments of Gastrointestinal Medical Oncology
| | - Lei He
- Departments of Gastrointestinal Medical Oncology
| | - Qingwei Li
- Departments of Gastrointestinal Medical Oncology
| | - Ji Tao
- Departments of Gastrointestinal Medical Oncology
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Focus on the Dynamics of Neutrophil-to-Lymphocyte Ratio in Cancer Patients Treated with Immune Checkpoint Inhibitors: A Meta-Analysis and Systematic Review. Cancers (Basel) 2022; 14:cancers14215297. [PMID: 36358716 PMCID: PMC9658132 DOI: 10.3390/cancers14215297] [Citation(s) in RCA: 32] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2022] [Revised: 10/25/2022] [Accepted: 10/26/2022] [Indexed: 11/17/2022] Open
Abstract
Background: A number of studies have reported an association between the dynamics of neutrophil-to-lymphocyte ratio (NLR) and clinical efficacy in patients treated with immune checkpoint inhibitors (ICIs), but there is still a lack of a meta-analysis or systematic review. Methods: PubMed, Embase, Web of Science, and the Cochrane Library were searched until September 2022 for studies reporting on the association between the change in NLR after ICI treatment and clinical outcomes. Outcome measures of interest included: change in NLR before and after treatment, overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). Results: A total of 4154 patients in 38 studies were included. The pooled percentage of patients with increased NLR was 49.7% (95CI%: 43.7−55.8%). Six studies discussing the change in NLR in patients with different tumor responses all showed that the NLR level in patients without response to immunotherapy may increase after ICI treatment. The upward trend in NLR was associated with shorter OS (pooled HR: 2.05, 95%CI: 1.79−2.35, p < 0.001) and PFS (pooled HR: 1.89, 95%CI: 1.66−2.14, p < 0.001) and higher ORR (pooled OR: 0.27, 95%CI: 0.19−0.39, p < 0.001), and downward trend in NLR was associated with longer OS (pooled HR: 0.49, 95%CI: 0.42−0.58, p < 0.001) and PFS (pooled HR: 0.55, 95%CI: 0.48−0.63, p < 0.001) and lower ORR (pooled OR: 3.26, 95%CI: 1.92−5.53, p < 0.001). In addition, post-treatment high NLR was associated with more impaired survival than baseline high NLR (pooled HR of baseline high NLR: 1.82, 95%CI: 1.52−2.18; pooled HR of post-treatment high NLR: 2.93, 95%CI: 2.26−3.81), but the NLR at different time points may have a similar predictive effect on PFS (pooled HR of baseline high NLR: 1.68, 95%CI: 1.44−1.97; pooled HR of post-treatment high NLR: 2.00, 95%CI: 1.54−2.59). Conclusions: The NLR level of tumor patients after ICI treatment is stable overall, but the NLR level in patients without response to immunotherapy may increase after ICI treatment. Patients with an upward trend in NLR after ICI treatment were associated with worse clinical outcomes; meanwhile, the downward trend in NLR was associated with better clinical outcomes. Post-treatment high NLR was associated with more impaired survival than baseline high NLR.
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Rebuzzi SE, Signori A, Stellato M, Santini D, Maruzzo M, De Giorgi U, Pedrazzoli P, Galli L, Zucali PA, Fantinel E, Carella C, Procopio G, Milella M, Boccardo F, Fratino L, Sabbatini R, Ricotta R, Panni S, Massari F, Sorarù M, Santoni M, Cortellini A, Prati V, Soto Parra H, Atzori F, Di Napoli M, Caffo O, Messina M, Morelli F, Prati G, Nolè F, Vignani F, Cavo A, Roviello G, Llaja Obispo MA, Porta C, Buti S, Fornarini G, Banna GL. The prognostic value of baseline and early variations of peripheral blood inflammatory ratios and their cellular components in patients with metastatic renal cell carcinoma treated with nivolumab: The Δ-Meet-URO analysis. Front Oncol 2022; 12:955501. [PMID: 36212433 PMCID: PMC9541611 DOI: 10.3389/fonc.2022.955501] [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: 05/28/2022] [Accepted: 08/23/2022] [Indexed: 11/14/2022] Open
Abstract
BACKGROUND Treatment choice for metastatic renal cell carcinoma (mRCC) patients is still based on baseline clinical and laboratory factors. METHODS By a pre-specified analysis of the Meet-URO 15 multicentric retrospective study enrolling 571 pretreated mRCC patients receiving nivolumab, baseline and early dynamic variations (Δ) of neutrophil, lymphocyte, and platelet absolute cell counts (ACC) and their inflammatory ratios (IR) were evaluated alongside their association with the best disease response and overall (OS) and progression-free survival (PFS). Multivariable analyses on OS and PFS between baseline and Δ ACC and IR values were investigated with receiving operating curves-based cut-offs. RESULTS The analysis included 422 mRCC patients. Neutrophil-to-lymphocyte ratio (NLR) increased over time due to consistent neutrophil increase (p < 0.001). Higher baseline platelets (p = 0.044) and lower lymphocytes (p = 0.018), increasing neutrophil Δ (p for time-group interaction <0.001), higher baseline IR values (NLR: p = 0.012, SII: p = 0.003, PLR: p = 0.003), increasing NLR and systemic immune-inflammatory index (SII) (i.e., NLR x platelets) Δ (p for interaction time-group = 0.0053 and 0.0435, respectively) were associated with disease progression. OS and PFS were significantly shorter in patients with baseline lower lymphocytes (p < 0.001 for both) and higher platelets (p = 0.004 and p < 0.001, respectively) alongside early neutrophils Δ (p = 0.046 and p = 0.033, respectively). Early neutrophils and NLR Δ were independent prognostic factors for both OS (p = 0.014 and p = 0.011, respectively) and PFS (p = 0.023 and p = 0.001, respectively), alongside baseline NLR (p < 0.001 for both) and other known prognostic variables. CONCLUSIONS Early neutrophils and NLR Δ may represent new dynamic prognostic factors with clinical utility for on-treatment decisions.
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Affiliation(s)
- Sara Elena Rebuzzi
- Medical Oncology Unit, Ospedale San Paolo, Savona, Italy
- Department of Internal Medicine and Medical Specialties (Di.M.I.), University of Genova, Genova, Italy
| | - Alessio Signori
- Department of Health Sciences, Section of Biostatistics, University of Genova, Genova, Italy
| | - Marco Stellato
- SS Oncologia Medica Genitourinaria, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy
| | - Daniele Santini
- Department of Medical Oncology, Università Campus Bio-Medico of Roma, Rome, Italy
| | - Marco Maruzzo
- Oncology Unit 1, Istituto Oncologico Veneto IOV - IRCCS, Padova, Italy
| | - Ugo De Giorgi
- Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, Italy
| | - Paolo Pedrazzoli
- Department of Internal Medicine and Medical Therapy, University of Pavia, Pavia, Italy
- Medical Oncology Unit, IRCCS Policlinico San Matteo, Pavia, Italy
| | - Luca Galli
- Medical Oncology Unit 2, Azienda Ospedaliera Universitaria Pisana, Pisa, Italy
| | - Paolo Andrea Zucali
- Department of Biomedical Sciences, Humanitas University, Milano, Italy
- Department of Oncology, IRCCS, Humanitas Clinical and Research Center, Milano, Italy
| | - Emanuela Fantinel
- Department of Oncology, Azienda Ospedaliera Universitaria Integrata di Verona, University of Verona, Verona, Italy
| | - Claudia Carella
- Division of Medical Oncology, IRCCS Istituto Tumori “Giovanni Paolo II”, Bari, Italy
| | - Giuseppe Procopio
- SS Oncologia Medica Genitourinaria, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy
| | - Michele Milella
- Department of Oncology, Azienda Ospedaliera Universitaria Integrata di Verona, University of Verona, Verona, Italy
| | - Francesco Boccardo
- Academic Unit of Medical Oncology, IRCCS Ospedale Policlinico San Martino of Genova, Genova, Italy
| | - Lucia Fratino
- Department of Medical Oncology, Centro di Riferimento Oncologico di Aviano CRO-IRCCS, Aviano, Italy
| | - Roberto Sabbatini
- Medical Oncology Unit, Department of Oncology and Hemathology, University Hospital of Modena, Modena, Italy
| | | | - Stefano Panni
- Medical Oncology Unit, ASSTl– Istituti Ospitalieri Cremona Hospital, Cremona, Italy
| | - Francesco Massari
- Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- Department of Experimental, Diagnostic and Specialty Medicine, S. Orsola-Malpighi University Hospital, University of Bologna, Bologna, Italy
| | | | | | - Alessio Cortellini
- Department of Surgery and Cancer, Imperial College London, Faculty of Medicine, Hammersmith Hospital, London, United Kingdom
- Department of Biotechnology and Applied Clinical Sciences, University of L’Aquila, L’Aquila, Italy
| | - Veronica Prati
- Department of Medical Oncology, Ospedale Michele e Pietro Ferrero, Verduno, Italy
| | - Hector Josè Soto Parra
- Department of Oncology, Medical Oncology, University Hospital Policlinico-San Marco, Catania, Italy
| | - Francesco Atzori
- Medical Oncology Department, University Hospital, University of Cagliari, Cagliari, Italy
| | - Marilena Di Napoli
- Department of Urology and Gynecology, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, Napoli, Italy
| | - Orazio Caffo
- Medical Oncology Department, Santa Chiara Hospital, Trento, Italy
| | - Marco Messina
- UOC Oncologia Medica, Istituto Fondazione G. Giglio, Cefalù, Italy
| | | | - Giuseppe Prati
- Department of Oncology and Advanced Technologies AUSL - IRCCS, Reggio Emilia, Italy
| | - Franco Nolè
- Medical Oncology Division of Urogenital and Head and Neck Tumors, IEO, European Institute of Oncology IRCCS, Milano, Italy
| | - Francesca Vignani
- Division of Medical Oncology, Ordine Mauriziano Hospital, Torino, Italy
| | - Alessia Cavo
- Oncology Unit, Villa Scassi Hospital, Genova, Italy
| | - Giandomenico Roviello
- Department of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Firenze, Firenze, Italy
| | | | - Camillo Porta
- Interdisciplinary Department of Medicine, University of Bari “A. Moro”, Bari, Italy
- Division of Medical Oncology, A.O.U. Consorziale Policlinico di Bari, Bari, Italy
| | - Sebastiano Buti
- Medical Oncology Unit, University Hospital of Parma, Parma, Italy
- Department of Medicine and Surgery, University of Parma, Parma, Italy
| | - Giuseppe Fornarini
- Medical Oncology Unit 1, IRCCS Ospedale Policlinico San Martino, Genova, Italy
| | - Giuseppe Luigi Banna
- Department of Oncology, Portsmouth Hospitals University NHS Trust, Portsmouth, United Kingdom
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Wang L, Zhu Y, Zhang B, Wang X, Mo H, Jiao Y, Xu J, Huang J. Prognostic and predictive impact of neutrophil-to-lymphocyte ratio and HLA-I genotyping in advanced esophageal squamous cell carcinoma patients receiving immune checkpoint inhibitor monotherapy. Thorac Cancer 2022; 13:1631-1641. [PMID: 35437954 PMCID: PMC9161342 DOI: 10.1111/1759-7714.14431] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2022] [Revised: 04/03/2022] [Accepted: 04/04/2022] [Indexed: 01/02/2023] Open
Abstract
Background Immune checkpoint inhibitors (ICIs) have become standard‐of‐care in patients with pretreated advanced esophageal squamous cell carcinoma (ESCC). However, reliable biomarkers for clinical outcomes are lacking for ICIs. The exploration of effective biomarkers is therefore needed to optimize patient benefit in the treatment of ESCC. Methods Sixty‐nine patients with advanced ESCC enrolled at one center from two prospective trials were consecutively analyzed. NLR was dynamically collected and high‐resolution HLA‐I genotyping were performed on genomic DNA. Overall response rate (ORR), median progression‐free survival (mPFS) and median overall survival (mOS) were investigated. Results Thirty‐three (47.8%) of 69 patients with baseline NLR ≥4 demonstrated significantly worse clinical outcomes (ORR 9.1% vs. 36.1%, p = 0.018; mPFS 1.8 vs. 3.2 months, hazard ratio [HR] 1.79, p = 0.026; mOS 7.4 vs. 11.0 months, HR 2.28, p = 0.008). An NLR decrease ≥20% at the first radiological evaluation was associated with longer OS (median, 14.0 vs. 7.9 months, p = 0.038). Eleven (15.9%) patients with HLA‐I homozygosity presented poorer clinical outcomes (ORR 0 vs. 27.6%, p = 0.056; mPFS 1.8 vs. 2.4 months, HR 3.37, p = 0.010; mOS 5.6 vs. 10.5 months, HR 3.97, p = 0.004). Patients with baseline NLR ≥4 and HLA‐I homozygosity had the worst outcome (ORR 0; mPFS 1.4 months; mOS 1.8 months) among all. The association between NLR, HLA‐I genotyping and clinical outcomes was independent of programmed death receptor ligand‐1 expression. Conclusions NLR and HLA‐I genotyping could have predictive and prognostic value in patients with advanced ESCC receiving camrelizumab, and the combination of biomarkers may help to identify more patient benefit from immunotherapy.
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Affiliation(s)
- Lin Wang
- Department of Medical Oncology, National Cancer Center/ National Clinical Research Center for Cancer/ Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Yanrong Zhu
- Department of Medical Oncology, National Cancer Center/ National Clinical Research Center for Cancer/ Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Bo Zhang
- Department of Medical Oncology, National Cancer Center/ National Clinical Research Center for Cancer/ Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Xi Wang
- Daycare Center, Peking University Cancer Hospital & Institute, Beijing, China
| | - Hongnan Mo
- Department of Medical Oncology, National Cancer Center/ National Clinical Research Center for Cancer/ Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Yuchen Jiao
- Laboratory of Cell and Molecular Biology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jiachen Xu
- Department of Medical Oncology, National Cancer Center/ National Clinical Research Center for Cancer/ Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Jing Huang
- Department of Medical Oncology, National Cancer Center/ National Clinical Research Center for Cancer/ Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
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Liu J, Shao J, Zhang C, Qin G, Liu J, Li M, Wu P, Zhao X, Zhang Y. Immuno-oncological role of 20S proteasome alpha-subunit 3 in aggravating the progression of esophageal squamous cell carcinoma. Eur J Immunol 2022; 52:338-351. [PMID: 34755333 DOI: 10.1002/eji.202149441] [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: 06/09/2021] [Revised: 10/11/2021] [Accepted: 11/03/2021] [Indexed: 11/05/2022]
Abstract
PSMA3, a member of the proteasome subunit, has been shown to play a major player in protein degradation. Reportedly, PSMA3 functions as a negative regulator in various cancers including colon, pancreatic and gastric cancers. However, the contributions of PSMA3 to the progression of esophageal squamous cell carcinoma (ESCC) and the underlying mechanism remain unclear. Therefore, in this study, we investigated whether PSMA3 is involved in ESCC progression and the potential underlying mechanism. The results revealed that PSMA3 was highly expressed in the ESCC tumor tissues and functioned as a negative indicator according to the data from The Cancer Genome Atlas (TCGA)/Gene Expression Omnibus (GEO) datasets and clinical patients' samples. Pathway enrichment analysis showed that PSMA3 was closely correlated with ESCC cancer stemness and the inflammatory response; however, this correlation was absent after knockdown of PSMA3 in vitro. We further demonstrated that PSMA3 suppressed CD8+ T-cells infiltration depending on the C-C motif chemokine ligand 3 (CCL3)/C-C motif chemokine receptor 5 (CCR5) axis. Collectively, these results demonstrate the role of PSMA3 in ESCC cancer stemness and the negative regulation of CD8 T-cells infiltration mediated by PSMA3. The results of this study may provide a potential target for the immuno-oncology effect of PSMA3 in ESCC therapy.
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Affiliation(s)
- Jinyan Liu
- Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, P. R. China
| | - Jingwen Shao
- Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, P. R. China
| | - Chaoqi Zhang
- Department of Thoracic Surgery, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China
| | - Guohui Qin
- Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, P. R. China
| | - Jiayin Liu
- School of Life Sciences, Zhengzhou University, Zhengzhou, Henan, P. R. China
| | - Miaomiao Li
- Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, P. R. China
| | - Peng Wu
- Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, P. R. China
| | - Xuan Zhao
- Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, P. R. China
| | - Yi Zhang
- Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, P. R. China
- School of Life Sciences, Zhengzhou University, Zhengzhou, Henan, P. R. China
- Cancer Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, P. R. China
- Key Laboratory for Tumor Immunology and Biotherapy of Henan Province, Zhengzhou, Henan, P. R. China
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Wu X, Han R, Zhong Y, Weng N, Zhang A. Correction to: Post treatment NLR is a predictor of response to immune checkpoint inhibitor therapy in patients with esophageal squamous cell carcinoma. Cancer Cell Int 2021; 21:693. [PMID: 34930249 PMCID: PMC8690400 DOI: 10.1186/s12935-021-02401-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/09/2021] [Indexed: 11/22/2022] Open
Affiliation(s)
- Xiaobin Wu
- Department of Gastrointestinal Surgery, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518033, China
| | - Runkun Han
- Department of Laboratory Medicine, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China
| | - Yanping Zhong
- Department of Health Management, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
| | - Nuoqing Weng
- Department of Gastrointestinal Surgery, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518033, China.
| | - Ao Zhang
- Department of Laboratory Medicine, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China.
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Chen X, Meng F, Jiang R. Neutrophil-to-Lymphocyte Ratio as a Prognostic Biomarker for Patients With Metastatic Renal Cell Carcinoma Treated With Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis. Front Oncol 2021; 11:746976. [PMID: 34900692 PMCID: PMC8660071 DOI: 10.3389/fonc.2021.746976] [Citation(s) in RCA: 40] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2021] [Accepted: 10/25/2021] [Indexed: 12/20/2022] Open
Abstract
There is increasing evidence to suggest that the neutrophil-to-lymphocyte ratio (NLR) is related to the prognosis of patients with renal cell carcinoma (RCC) treated with immune checkpoint inhibitors (ICIs). However, these findings are inconsistent. The present study was performed with the aim of exploring the utility of NLR in patients with RCC treated with ICIs. For this purpose, a comprehensive search of PubMed, Web of Science, and Embase was performed to find studies evaluating the prognostic value of NLR. The overall survival (OS) and progression-free survival (PFS) were the assessed clinical outcomes. All statistical analysis was performed using Stata version 12.0 software. The combined hazard ratios (HRs) and 95% confidence intervals (CIs) of NLR for OS and PFS were calculated using the random-effect models. Heterogeneity was evaluated based on the I 2 value and Cochran's Q test. Egger's and Begg's tests were applied to precisely assess the publication bias. The "trim and fill" method was adopted to perform the sensitivity analysis to determine whether the results were stable. In total, 12 studies encompassing 1,275 patients were included in the final analysis. The results revealed that a high NLR at baseline or pre-therapy was associated with a poor OS (HR, 2.23; 95% CI, 1.84-2.70; p < 0.001) and PFS (HR, 1.78; 95% CI, 1.72-2.09; p < 0.001). During the course of treatment, a decrease in the NLR was associated with a significantly longer OS (HR, 0.34; 95% CI, 0.20-0.56; p < 0.001) and PFS (HR, 0.44; 95% CI, 0.30-0.63; p < 0.001) compared to an increase in NLR. As a preliminary screening of other risk factors, age, sex, race, and IMDC risk may have a certain prognostic value for RCC treated with ICIs. People over 70 years old had better OS compared to people younger than 70 (HR, 0.65; 95% CI, 0.48-0.89). Non-Caucasians treated with immunotherapy had a worse OS (HR, 8.67; 95% CI, 2.87-26.2) and PFS (HR, 2.65; 95% CI, 1.28-5.48) than Caucasians. Males had a worse OS than females (HR, 1.48; 95% CI, 1.14-1.93). Compared with the IMDC favorable risk group, the OS of the IMDC poor risk group was worse (HR, 2.59; 95% CI, 1.56-4.32). There was no significant publication bias or heterogeneity observed in the present study. On the whole, the present study demonstrated that an elevated NLR is associated with an adverse OS and PFS in patients with RCC treated with ICIs. The NLR may thus be used as a readily available prognostic biomarker for these patients. Age, sex, race, and IMDC risk may have potential predictive value for the prognosis of RCC treated with ICIs. However, further investigations are warranted to validate these results.
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Affiliation(s)
- Xiuqiong Chen
- Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China.,Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.,Tianjin's Clinical Research Center for Cancer, Tianjin, China.,Department of Thoracic Oncology, Tianjin Lung Cancer Center, Tianjin Cancer Institute and Hospital, Tianjin Medical University, Tianjin, China
| | - Fanqiao Meng
- Department of Hematology, Tianjin Medical University General Hospital, Tianjin, China
| | - Richeng Jiang
- Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China.,Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.,Tianjin's Clinical Research Center for Cancer, Tianjin, China.,Department of Thoracic Oncology, Tianjin Lung Cancer Center, Tianjin Cancer Institute and Hospital, Tianjin Medical University, Tianjin, China
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