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

Autor:	Wang W; Department of Radiation Oncology, University Hospitals Cleveland Medical Center/Seidman Cancer Center, Cleveland, Ohio.; Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, Ohio., Huang L; Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, Newcastle-upon-Tyne, United Kingdom., Jin JY; Department of Radiation Oncology, University Hospitals Cleveland Medical Center/Seidman Cancer Center, Cleveland, Ohio.; Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, Ohio., Pi W; Department of Radiation Oncology, Indiana University School of Medicine, Indianapolis, Indiana., Ellsworth SG; Department of Radiation Oncology, Indiana University School of Medicine, Indianapolis, Indiana., Jolly S; Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan., Mellor AL; Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, Newcastle-upon-Tyne, United Kingdom., Machtay M; Department of Radiation Oncology, University Hospitals Cleveland Medical Center/Seidman Cancer Center, Cleveland, Ohio.; Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, Ohio., Kong FS; Department of Radiation Oncology, University Hospitals Cleveland Medical Center/Seidman Cancer Center, Cleveland, Ohio. fxk132@case.edu/kong0001@hku.hk.; Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, Ohio.; Departments of Clinical Oncology, Hong Kong University Shenzhen Hospital, and Hong Kong University, Hong Kong, China.
Jazyk:	angličtina
Zdroj:	Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2020 Jan 01; Vol. 26 (1), pp. 282-289. Date of Electronic Publication: 2019 Aug 30.
DOI:	10.1158/1078-0432.CCR-19-1202
Abstrakt:	Purpose: We recently reported that indoleamine 2, 3-dioxygenase (IDO) activity is significantly correlated with more distant metastasis and worse survival. 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% confidence interval (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 more post-RT in the 3DCRT patients with a median increase 0.721 ng/mL, compared to that of SBRT patients (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 immunosuppressive effect than 3DCRT, as measured by IDO. (©2019 American Association for Cancer Research.)
Databáze:	MEDLINE
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