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A Validation Study on IDO Immune Biomarkers for Survival Prediction in Non–Small Cell Lung Cancer: Radiation Dose Fractionation Effect in Early-Stage Disease

Lookup NU author(s): Dr Lei HuangORCiD, Emeritus Professor Andrew MellorORCiD

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This is the authors' accepted manuscript of an article that has been published in its final definitive form by American Association for Cancer Research, 2020.

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Abstract

We recently reported that indoleamine 2, 3-dioxygenase (IDO) activity is inversely related to distant metastasis risk and survival in stage III non-small cell lung cancer (NSCLC). The present study examined whether radiotherapy (RT) dose fractionation correlates with IDO-mediated immune activity in patients with early-stage NSCLC.METHODS:Patients with newly diagnosed stage I-II NSCLC treated with either conventionally fractionated 3-dimensional conformal radiotherapy (3DCRT) or stereotactic body radiotherapy (SBRT) were analyzed. Levels of two key molecules associated with the IDO immune checkpoint, serum kynurenine and the kynurenine:tryptophan ratio (K:T ratio), were measured at pre-RT, during-RT, and 3-month post-RT. The relationship between disease control outcomes [overall survival (OS), progression free survival, and local/regional/distant failure rates] and absolute levels of these markers, as well as dynamic changes in their levels during RT, was studied.RESULTS:Fifty-six patients (SBRT=28, 3DCRT=28) with early stage NSCLC were studied. In all patients, higher kynurenine post-RT was significantly associated with worse OS (HR, 1.25, 95% CI 1.01-1.55, P=0.044). No statistically significant differences in absolute kynurenine levels or the K:T ratio were observed in patients treated with 3DCRT or SBRT at any of the three time points. However, the absolute kynurenine levels rose significantly post-RT in the 3DCRT patients with the median increase (0.721 ng/mL), whereas SBRT patients did not (0.115 ng/mL); P=0.022.CONCLUSIONS:This study validated that elevated IDO activity correlated with worse survival outcomes in patients with early-stage NSCLC treated with definitive RT. Hypofractionated SBRT may have less immune suppressive effect than 3DCRT, as measured by IDO.


Publication metadata

Author(s): Wang W, Huang L, Jin JY, Pi W, Ellsworth SG, Jolly S, Mellor AL, Machtay M, Kong FS

Publication type: Article

Publication status: Published

Journal: Clinical Cancer Research

Year: 2020

Volume: 26

Issue: 1

Pages: 282-289

Print publication date: 01/01/2020

Online publication date: 30/08/2019

Acceptance date: 27/07/2019

Date deposited: 02/09/2019

ISSN (print): 1078-0432

ISSN (electronic): 1557-3265

Publisher: American Association for Cancer Research

URL: https://doi.org/10.1158/1078-0432.CCR-19-1202

DOI: 10.1158/1078-0432.CCR-19-1202

PubMed id: 31471311


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