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European Radiology
Published in: European Radiology 12/2022

31-05-2022 | Computed Tomography | Imaging Informatics and Artificial Intelligence

Development and validation of a computed tomography–based immune ecosystem diversity index as an imaging biomarker in non-small cell lung cancer

Authors: Lan He, Zhen-Hui Li, Li-Xu Yan, Xin Chen, Sebastian Sanduleanu, Wen-Zhao Zhong, Phillippe Lambin, Zhao-Xiang Ye, Ying-Shi Sun, Yu-Lin Liu, Jin-Rong Qu, Lin Wu, Chang-Ling Tu, Madeleine Scrivener, Thierry Pieters, Emmanuel Coche, Qian Yang, Mei Yang, Chang-Hong Liang, Yan-Qi Huang, Zai-Yi Liu

Published in: European Radiology | Issue 12/2022

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Abstract

Objectives

To date, there are no data on the noninvasive surrogate of intratumoural immune status that could be prognostic of survival outcomes in non-small cell lung cancer (NSCLC). We aimed to develop and validate the immune ecosystem diversity index (iEDI), an imaging biomarker, to indicate the intratumoural immune status in NSCLC. We further investigated the clinical relevance of the biomarker for survival prediction.

Methods

In this retrospective study, two independent NSCLC cohorts (Resec1, n = 149; Resec2, n = 97) were included to develop and validate the iEDI to classify the intratumoural immune status. Paraffin-embedded resected specimens in Resec1 and Resec2 were stained by immunohistochemistry, and the density percentiles of CD3+, CD4+, and CD8+ T cells to all cells were quantified to estimate intratumoural immune status. Then, EDI features were extracted using preoperative computed tomography to develop an imaging biomarker, called iEDI, to determine the immune status. The prognostic value of iEDI was investigated on NSCLC patients receiving surgical resection (Resec1; Resec2; internal cohort Resec3, n = 419; external cohort Resec4, n = 96; and TCIA cohort Resec5, n = 55).

Results

iEDI successfully classified immune status in Resec1 (AUC 0.771, 95% confidence interval [CI] 0.759–0.783; and 0.770 through internal validation) and Resec2 (0.669, 0.647–0.691). Patients with higher iEDI-score had longer overall survival (OS) in Resec3 (unadjusted hazard ratio 0.335, 95%CI 0.206–0.546, p < 0.001), Resec4 (0.199, 0.040–1.000, p < 0.001), and TCIA (0.303, 0.098–0.944, p = 0.001).

Conclusions

iEDI is a non-invasive surrogate of intratumoural immune status and prognostic of OS for NSCLC patients receiving surgical resection.

Key Points

• Decoding tumour immune microenvironment enables advanced biomarkers identification.
• Immune ecosystem diversity index characterises intratumoural immune status noninvasively.
• Immune ecosystem diversity index is prognostic for NSCLC patients.
Appendix
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Metadata
Title
Development and validation of a computed tomography–based immune ecosystem diversity index as an imaging biomarker in non-small cell lung cancer
Authors
Lan He
Zhen-Hui Li
Li-Xu Yan
Xin Chen
Sebastian Sanduleanu
Wen-Zhao Zhong
Phillippe Lambin
Zhao-Xiang Ye
Ying-Shi Sun
Yu-Lin Liu
Jin-Rong Qu
Lin Wu
Chang-Ling Tu
Madeleine Scrivener
Thierry Pieters
Emmanuel Coche
Qian Yang
Mei Yang
Chang-Hong Liang
Yan-Qi Huang
Zai-Yi Liu
Publication date
31-05-2022
Publisher
Springer Berlin Heidelberg
Published in
European Radiology / Issue 12/2022
Print ISSN: 0938-7994
Electronic ISSN: 1432-1084
DOI
https://doi.org/10.1007/s00330-022-08873-6

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