Lookup NU author(s): Dr Lei Huang,
Professor Andrew Mellor
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.
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.
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
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
PubMed id: 31471311
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