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      Inflammatory biomarkers as predictors of immune activation to different irradiated sites and short-term efficacy in advanced squamous cell esophageal carcinoma received radioimmunotherapy

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          Abstract

          Purpose

          The present study aimed to compare immune activation among different irradiated sites and identify potential short-term efficacy prognostic factors in patients with advanced squamous cell esophageal carcinoma (ESCC) who received radiotherapy (RT) and immunotherapy.

          Patients and methods

          We recorded the clinical characteristics, blood cell counts, and derived blood index ratios, including neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII), at three time points (before, during, and after RT) in 121 patients with advanced ESCC who had received RT and immunotherapy. Chi-square test and univariate and multivariate logistic regression analyses were used to calculate the relationships among inflammatory biomarkers (IBs), irradiated sites, and short-term efficacy.

          Results

          Delta-IBs were calculated as (medio-IBs - pre-IBs) ÷ pre-IBs. The medians of delta-LMR, and delta-ALC were the highest, whereas the median of delta-SII was the lowest in patients with brain radiation. Treatment responses were observed within 3 months after RT or until the beginning of the next line therapy, and the disease control rate (DCR) was 75.2%. The areas under the receiver operating characteristic curve (AUCs) for delta-NLR and delta-SII were 0.723 (p = 0.001) and 0.725 (p < 0.001), respectively. Multivariate logistic regression analysis showed that the treatment lines of immunotherapy (odds ratio [OR], 4.852; 95% confidence interval [CI], 1.595-14.759; p = 0.005) and delta-SII (OR, 5.252; 95% CI, 1.048-26.320; p = 0.044) were independent indicators of short-term efficacy.

          Conclusion

          In this study, we found that RT to the brain had a stronger immune activation effect than RT to extracranial organs. We also found that earlier-line immunotherapy plus RT and a decrease in SII during RT may generate better short-term efficacy in advanced ESCC.

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          Most cited references37

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          Cancer statistics, 2022

          Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths in the United States and compiles the most recent data on population-based cancer occurrence and outcomes. Incidence data (through 2018) were collected by the Surveillance, Epidemiology, and End Results program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data (through 2019) were collected by the National Center for Health Statistics. In 2022, 1,918,030 new cancer cases and 609,360 cancer deaths are projected to occur in the United States, including approximately 350 deaths per day from lung cancer, the leading cause of cancer death. Incidence during 2014 through 2018 continued a slow increase for female breast cancer (by 0.5% annually) and remained stable for prostate cancer, despite a 4% to 6% annual increase for advanced disease since 2011. Consequently, the proportion of prostate cancer diagnosed at a distant stage increased from 3.9% to 8.2% over the past decade. In contrast, lung cancer incidence continued to decline steeply for advanced disease while rates for localized-stage increased suddenly by 4.5% annually, contributing to gains both in the proportion of localized-stage diagnoses (from 17% in 2004 to 28% in 2018) and 3-year relative survival (from 21% to 31%). Mortality patterns reflect incidence trends, with declines accelerating for lung cancer, slowing for breast cancer, and stabilizing for prostate cancer. In summary, progress has stagnated for breast and prostate cancers but strengthened for lung cancer, coinciding with changes in medical practice related to cancer screening and/or treatment. More targeted cancer control interventions and investment in improved early detection and treatment would facilitate reductions in cancer mortality.
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            Tumour heterogeneity and resistance to cancer therapies

            Cancer is a dynamic disease. During the course of disease, cancers generally become more heterogeneous. As a result of this heterogeneity, the bulk tumour might include a diverse collection of cells harbouring distinct molecular signatures with differential levels of sensitivity to treatment. This heterogeneity might result in a non-uniform distribution of genetically distinct tumour-cell subpopulations across and within disease sites (spatial heterogeneity) or temporal variations in the molecular makeup of cancer cells (temporal heterogeneity). Heterogeneity provides the fuel for resistance; therefore, an accurate assessment of tumour heterogeneity is essential for the development of effective therapies. Multiregion sequencing, single-cell sequencing, analysis of autopsy samples, and longitudinal analysis of liquid biopsy samples are all emerging technologies with considerable potential to dissect the complex clonal architecture of cancers. In this Review, we discuss the driving forces behind intratumoural heterogeneity and the current approaches used to combat this heterogeneity and its consequences. We also explore how clinical assessments of tumour heterogeneity might facilitate the development of more-effective personalized therapies.
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              Cancer-related inflammation and treatment effectiveness.

              Inflammation is a recognised hallmark of cancer that substantially contributes to the development and progression of malignancies. In established cancers, there is increasing evidence for the roles that local immune response and systemic inflammation have in progression of tumours and survival of patients with cancer. This knowledge provides an opportunity to target these inflammatory responses to improve patient outcomes. In this Review, we examine the complex interplay between local immune responses and systemic inflammation, and their influence on clinical outcomes, and propose potential anti-inflammatory interventions for patients with cancer.
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                Author and article information

                Contributors
                Journal
                Front Oncol
                Front Oncol
                Front. Oncol.
                Frontiers in Oncology
                Frontiers Media S.A.
                2234-943X
                10 May 2023
                2023
                : 13
                : 1117648
                Affiliations
                [1] 1Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences , Jinan, Shandong, China
                [2] 2Department of Radiation Oncology, School of Medicine, Shandong University , Jinan, China
                Author notes

                Edited by: Kui Zhang, The University of Chicago, United States

                Reviewed by: Lujun Shen, Sun Yat-sen University Cancer Center (SYSUCC), China; Zhangyuan Yin, Broad Institute, United States; Rongyu Zhang, University of Washington, United States

                *Correspondence: Xue Meng, mengxuesdzl@ 123456163.com ; Xiao Han, hxzbb1983@ 123456163.com
                Article
                10.3389/fonc.2023.1117648
                10206221
                989554ad-e6e8-435a-b540-f08d2dcc278d
                Copyright © 2023 Li, Cai, Gao, Meng and Han

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 06 December 2022
                : 27 April 2023
                Page count
                Figures: 3, Tables: 3, Equations: 0, References: 37, Pages: 9, Words: 3823
                Funding
                Funded by: National Natural Science Foundation of China , doi 10.13039/501100001809;
                Award ID: 81972864, 82172720
                Funded by: Science and Technology Support Plan for Youth Innovation of Colleges and Universities of Shandong Province of China , doi 10.13039/501100018627;
                Award ID: 2019KJL001
                This study was supported by National Natural Science Foundation of China (81972864 and 82172720), Science and Technology Support Plan for Youth Innovation Teams of Universities in Shandong Province (2019KJL001), Bethune Translational Medicine Research Foundation for Tumor Radiotherapy (flzh202106).
                Categories
                Oncology
                Original Research
                Custom metadata
                Gastrointestinal Cancers: Gastric and Esophageal Cancers

                Oncology & Radiotherapy
                squamous cell esophageal carcinoma,inflammatory biomarkers,immune activation,irradiated sites,short-term efficacy

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