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.
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Abbreviations
- AJCC:
-
American Joint Committee Cancer
- AUC:
-
Area under the ROC curve
- CI:
-
Confidence interval
- iAUC:
-
Integrated area under the ROC curve
- iBS:
-
Integrated Brier score
- iEDI:
-
Immune ecosystem diversity index
- LASSO:
-
The least absolute shrinkage and selection operator
- NCCN:
-
National Comprehensive Cancer Network
- NNE:
-
Nearest Neighbor Estimation
- NSCLC:
-
Non-small cell lung cancer
- OS:
-
Overall survival
- ROC:
-
Receiver operating characteristic
- TIME:
-
Tumour immune microenvironment
- TNM:
-
Tumour-node-metastasis
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Acknowledgements
We thank The Cancer Imaging Archive.
Funding
This study was supported by the National Key Research and Development Program of China (grant number 2021YFF1201003), the Key R&D Program of Guangdong Province of China (grant number 2021B0101420006), the National Science Fund for Distinguished Young Scholars (grant number 81925023), and the National Natural Scientific Foundation of China (grant number 81771912, 81901910, 82071892, and 82001986), the High-level Hospital Construction Project (DFJHBF202105). The funding sources had no involvement in study design, in the collection, analysis, and interpretation of data, in the writing of the report, and in the decision to submit the article for publication.
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The scientific guarantor of this publication is Zaiyi Liu.
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• retrospective
• prognostic study
• multicentre study
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He, L., Li, ZH., Yan, LX. et al. Development and validation of a computed tomography–based immune ecosystem diversity index as an imaging biomarker in non-small cell lung cancer. Eur Radiol 32, 8726–8736 (2022). https://doi.org/10.1007/s00330-022-08873-6
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DOI: https://doi.org/10.1007/s00330-022-08873-6