Radiation-induced Eosinophil Increase Ratio Predicts Patient Outcomes in Non-small Celllung Cancer

Overview

Journal Front Oncol

Specialty Oncology

Date 2022 Oct 24

PMID 36276060

Authors

Nuo-Han Wang

Xin Zhang

Jiang-Dong Sui

Ying Wang

Yong-Zhong Wu

Qian-Qian Lei

Hong-Lei Tu

Li-Na Yang

Yun-Chang Liu

Meng-Qi Yang

Hao-Nan Yang

Dan Li

Zheng Lei

Affiliations

Soon will be listed here.

Abstract

Background And Purpose: Radiotherapy (RT) is a double-edged sword in regulating immune responses. This study aimed to investigate the impact of thoracic RT on circulating eosinophils and its association with patient outcomes in non-small cell lung cancer (NSCLC).

Materials And Methods: This retrospective study included 240 patients with advanced NSCLC treated with definitive thoracic RT from January 2012 to January 2020. Statistics included Kaplan-Meier analysis of overall survival (OS) and progression-free survival (PFS), multivariate Cox analyses to identify significant variables, and Spearman's correlation to qualify the relationship between dose-volume histogram (DVH) parameters and EIR.

Results: Absolute eosinophil counts (AECs) showed an increasing trend during RT and an obvious peak in the 1 month after RT. Thresholds of eosinophil increase ratio (EIR) at the 1 month after RT for both OS and PFS were 1.43. Patients with high EIR above 1.43 experienced particularly favorable clinical outcomes (five-year OS: 21% versus 10%, P<0.0001; five-year PFS: 10% versus 8%, P=0.014), but may not derive PFS benefit from the addition of chemotherapy to RT. The higher a patient's EIR, the larger the potential benefit in the absence of chemotherapy. DVH parameters including heart mean dose and heart V10 were negatively associated with EIR. None of these DVH parameters was correlated with the clinical outcomes.

Conclusion: EIR may serve as a potential biomarker to predict OS and PFS in NSCLC patients treated with RT. These findings require prospective studies to evaluate the role of such prognostic marker to identify patients at risk to tailor interventions.

References

McLaughlin M, Patin E, Pedersen M, Wilkins A, Dillon M, Melcher A . Inflammatory microenvironment remodelling by tumour cells after radiotherapy. Nat Rev Cancer. 2020; 20(4):203-217. DOI: 10.1038/s41568-020-0246-1. View

Faivre-Finn C, Snee M, Ashcroft L, Appel W, Barlesi F, Bhatnagar A . Concurrent once-daily versus twice-daily chemoradiotherapy in patients with limited-stage small-cell lung cancer (CONVERT): an open-label, phase 3, randomised, superiority trial. Lancet Oncol. 2017; 18(8):1116-1125. PMC: 5555437. DOI: 10.1016/S1470-2045(17)30318-2. View

Carretero R, Sektioglu I, Garbi N, Salgado O, Beckhove P, Hammerling G . Eosinophils orchestrate cancer rejection by normalizing tumor vessels and enhancing infiltration of CD8(+) T cells. Nat Immunol. 2015; 16(6):609-17. DOI: 10.1038/ni.3159. View

Upadhyay R, Venkatesulu B, Giridhar P, Kim B, Sharma A, Elghazawy H . Risk and impact of radiation related lymphopenia in lung cancer: A systematic review and meta-analysis. Radiother Oncol. 2021; 157:225-233. DOI: 10.1016/j.radonc.2021.01.034. View

Nielsen H, Hansen U, Christensen I, Reimert C, Brunner N, Moesgaard F . Independent prognostic value of eosinophil and mast cell infiltration in colorectal cancer tissue. J Pathol. 2000; 189(4):487-95. DOI: 10.1002/(SICI)1096-9896(199912)189:4<487::AID-PATH484>3.0.CO;2-I. View

Formenti S, Demaria S . Combining radiotherapy and cancer immunotherapy: a paradigm shift. J Natl Cancer Inst. 2013; 105(4):256-65. PMC: 3576324. DOI: 10.1093/jnci/djs629. View

Schwartz L, Litiere S, de Vries E, Ford R, Gwyther S, Mandrekar S . RECIST 1.1-Update and clarification: From the RECIST committee. Eur J Cancer. 2016; 62:132-7. PMC: 5737828. DOI: 10.1016/j.ejca.2016.03.081. View

Abravan A, Faivre-Finn C, Kennedy J, McWilliam A, Van Herk M . Radiotherapy-Related Lymphopenia Affects Overall Survival in Patients With Lung Cancer. J Thorac Oncol. 2020; 15(10):1624-1635. DOI: 10.1016/j.jtho.2020.06.008. View

Allemani C, Weir H, Carreira H, Harewood R, Spika D, Wang X . Global surveillance of cancer survival 1995-2009: analysis of individual data for 25,676,887 patients from 279 population-based registries in 67 countries (CONCORD-2). Lancet. 2014; 385(9972):977-1010. PMC: 4588097. DOI: 10.1016/S0140-6736(14)62038-9. View

10.

Gebhardt C, Sevko A, Jiang H, Lichtenberger R, Reith M, Tarnanidis K . Myeloid Cells and Related Chronic Inflammatory Factors as Novel Predictive Markers in Melanoma Treatment with Ipilimumab. Clin Cancer Res. 2015; 21(24):5453-9. DOI: 10.1158/1078-0432.CCR-15-0676. View

11.

Dillon M, Bergerhoff K, Pedersen M, Whittock H, Crespo-Rodriguez E, Patin E . ATR Inhibition Potentiates the Radiation-induced Inflammatory Tumor Microenvironment. Clin Cancer Res. 2019; 25(11):3392-3403. PMC: 6551222. DOI: 10.1158/1078-0432.CCR-18-1821. View

12.

Falcke S, Ruhle P, Deloch L, Fietkau R, Frey B, Gaipl U . Clinically Relevant Radiation Exposure Differentially Impacts Forms of Cell Death in Human Cells of the Innate and Adaptive Immune System. Int J Mol Sci. 2018; 19(11). PMC: 6274975. DOI: 10.3390/ijms19113574. View

13.

Fujii M, Yamashita T, Ishiguro R, Tashiro M, Kameyama K . Significance of epidermal growth factor receptor and tumor associated tissue eosinophilia in the prognosis of patients with nasopharyngeal carcinoma. Auris Nasus Larynx. 2002; 29(2):175-81. DOI: 10.1016/s0385-8146(01)00135-3. View

14.

Joseph N, McWilliam A, Kennedy J, Haslett K, Mahil J, Gavarraju A . Post-treatment lymphocytopaenia, integral body dose and overall survival in lung cancer patients treated with radical radiotherapy. Radiother Oncol. 2019; 135:115-119. DOI: 10.1016/j.radonc.2019.03.008. View

15.

Chen D, Patel R, Verma V, Ramapriyan R, Barsoumian H, Cortez M . Interaction between lymphopenia, radiotherapy technique, dosimetry, and survival outcomes in lung cancer patients receiving combined immunotherapy and radiotherapy. Radiother Oncol. 2020; 150:114-120. DOI: 10.1016/j.radonc.2020.05.051. View

16.

Wirsdorfer F, Jendrossek V . The Role of Lymphocytes in Radiotherapy-Induced Adverse Late Effects in the Lung. Front Immunol. 2016; 7:591. PMC: 5155013. DOI: 10.3389/fimmu.2016.00591. View

17.

Chu X, Zhao J, Zhou J, Zhou F, Jiang T, Jiang S . Association of baseline peripheral-blood eosinophil count with immune checkpoint inhibitor-related pneumonitis and clinical outcomes in patients with non-small cell lung cancer receiving immune checkpoint inhibitors. Lung Cancer. 2020; 150:76-82. DOI: 10.1016/j.lungcan.2020.08.015. View

18.

Yovino S, Kleinberg L, Grossman S, Narayanan M, Ford E . The etiology of treatment-related lymphopenia in patients with malignant gliomas: modeling radiation dose to circulating lymphocytes explains clinical observations and suggests methods of modifying the impact of radiation on immune cells. Cancer Invest. 2013; 31(2):140-4. PMC: 3991115. DOI: 10.3109/07357907.2012.762780. View

19.

Nishikawa D, Suzuki H, Beppu S, Terada H, Sawabe M, Kadowaki S . Eosinophil prognostic scores for patients with head and neck squamous cell carcinoma treated with nivolumab. Cancer Sci. 2020; 112(1):339-346. PMC: 7780035. DOI: 10.1111/cas.14706. View

20.

Cheng J, Luo W, Sun C, Jin Z, Zeng X, Alexander P . Radiation-induced eosinophils improve cytotoxic T lymphocyte recruitment and response to immunotherapy. Sci Adv. 2021; 7(5). PMC: 7846170. DOI: 10.1126/sciadv.abc7609. View