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

TitleA Validation Study on IDO Immune Biomarkers for Survival Prediction in Non–Small Cell Lung Cancer: Radiation Dose Fractionation Effect in Early-Stage Disease
Authors
Keywordsadult
aged
amino acid blood level
cancer chemotherapy
cancer staging
Issue Date2020
PublisherAmerican Association for Cancer Research. The Journal's web site is located at http://clincancerres.aacrjournals.org/
Citation
Clinical Cancer Research, 2020, v. 26 n. 1, p. 282-289 How to Cite?
AbstractPurpose: 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.
DescriptionLink to Full access
Persistent Identifierhttp://hdl.handle.net/10722/293326
ISSN
2020 Impact Factor: 12.531
2020 SCImago Journal Rankings: 5.427
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorWang, W-
dc.contributor.authorHuang, L-
dc.contributor.authorJin, JY-
dc.contributor.authorPi, W-
dc.contributor.authorEllsworth, SG-
dc.contributor.authorJolly, S-
dc.contributor.authorMellor, AL-
dc.contributor.authorMachtay, M-
dc.contributor.authorKong, FMS-
dc.date.accessioned2020-11-23T08:15:08Z-
dc.date.available2020-11-23T08:15:08Z-
dc.date.issued2020-
dc.identifier.citationClinical Cancer Research, 2020, v. 26 n. 1, p. 282-289-
dc.identifier.issn1078-0432-
dc.identifier.urihttp://hdl.handle.net/10722/293326-
dc.descriptionLink to Full access-
dc.description.abstractPurpose: 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.-
dc.languageeng-
dc.publisherAmerican Association for Cancer Research. The Journal's web site is located at http://clincancerres.aacrjournals.org/-
dc.relation.ispartofClinical Cancer Research-
dc.subjectadult-
dc.subjectaged-
dc.subjectamino acid blood level-
dc.subjectcancer chemotherapy-
dc.subjectcancer staging-
dc.titleA Validation Study on IDO Immune Biomarkers for Survival Prediction in Non–Small Cell Lung Cancer: Radiation Dose Fractionation Effect in Early-Stage Disease-
dc.typeArticle-
dc.identifier.emailKong, FMS: kong0001@hku.hk-
dc.identifier.authorityKong, FMS=rp02508-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1158/1078-0432.CCR-19-1202-
dc.identifier.pmid31471311-
dc.identifier.hkuros319527-
dc.identifier.volume26-
dc.identifier.issue1-
dc.identifier.spage282-
dc.identifier.epage289-
dc.identifier.isiWOS:000505668000031-
dc.publisher.placeUnited States-
dc.identifier.issnl1078-0432-

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