Toggle Main Menu Toggle Search

Open Access padlockePrints

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 Huang, Professor Andrew Mellor

Downloads


Licence

This is the authors' accepted manuscript of an article that has been published in its final definitive form by American Association for Cancer Research, 2019.

For re-use rights please refer to the publisher's terms and conditions.


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: 2019

Issue: ePub ahead of Print

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


Altmetrics

Altmetrics provided by Altmetric


Actions

Find at Newcastle University icon    Link to this publication


Share