TY - JOUR
T1 - Radiation-induced lung toxicity in non-small-cell lung cancer
T2 - Understanding the interactions of clinical factors and cytokines with the dose-toxicity relationship
AU - Hawkins, Peter G.
AU - Boonstra, Philip S.
AU - Hobson, Stephen T.
AU - Hearn, Jason W.D.
AU - Hayman, James A.
AU - Ten Haken, Randall K.
AU - Matuszak, Martha M.
AU - Stanton, Paul
AU - Kalemkerian, Gregory P.
AU - Ramnath, Nithya
AU - Lawrence, Theodore S.
AU - Schipper, Matthew J.
AU - (Spring) Kong, Feng Ming
AU - Jolly, Shruti
N1 - Publisher Copyright:
© 2017 Elsevier B.V.
PY - 2017/10
Y1 - 2017/10
N2 - Background and purpose Current methods to estimate risk of radiation-induced lung toxicity (RILT) rely on dosimetric parameters. We aimed to improve prognostication by incorporating clinical and cytokine data, and to investigate how these factors may interact with the effect of mean lung dose (MLD) on RILT. Materials and methods Data from 125 patients treated from 2004 to 2013 with definitive radiotherapy for stages I-III NSCLC on four prospective clinical trials were analyzed. Plasma levels of 30 cytokines were measured pretreatment, and at 2 and 4 weeks midtreatment. Penalized logistic regression models based on combinations of MLD, clinical factors, and cytokine levels were developed. Cross-validated estimates of log-likelihood and area under the receiver operating characteristic curve (AUC) were used to assess accuracy. Results In prognosticating grade 3 or greater RILT by MLD alone, cross-validated log-likelihood and AUC were −28.2 and 0.637, respectively. Incorporating clinical features and baseline cytokine levels increased log-likelihood to −27.6 and AUC to 0.669. Midtreatment cytokine data did not further increase log-likelihood or AUC. Of the 30 cytokines measured, higher levels of 13 decreased the effect of MLD on RILT, corresponding to a lower odds ratio for RILT per Gy MLD, while higher levels of 4 increased the association. Conclusions Although the added prognostic benefit from cytokine data in our model was modest, understanding how clinical and biologic factors interact with the MLD-RILT relationship represents a novel framework for understanding and investigating the multiple factors contributing to radiation-induced toxicity.
AB - Background and purpose Current methods to estimate risk of radiation-induced lung toxicity (RILT) rely on dosimetric parameters. We aimed to improve prognostication by incorporating clinical and cytokine data, and to investigate how these factors may interact with the effect of mean lung dose (MLD) on RILT. Materials and methods Data from 125 patients treated from 2004 to 2013 with definitive radiotherapy for stages I-III NSCLC on four prospective clinical trials were analyzed. Plasma levels of 30 cytokines were measured pretreatment, and at 2 and 4 weeks midtreatment. Penalized logistic regression models based on combinations of MLD, clinical factors, and cytokine levels were developed. Cross-validated estimates of log-likelihood and area under the receiver operating characteristic curve (AUC) were used to assess accuracy. Results In prognosticating grade 3 or greater RILT by MLD alone, cross-validated log-likelihood and AUC were −28.2 and 0.637, respectively. Incorporating clinical features and baseline cytokine levels increased log-likelihood to −27.6 and AUC to 0.669. Midtreatment cytokine data did not further increase log-likelihood or AUC. Of the 30 cytokines measured, higher levels of 13 decreased the effect of MLD on RILT, corresponding to a lower odds ratio for RILT per Gy MLD, while higher levels of 4 increased the association. Conclusions Although the added prognostic benefit from cytokine data in our model was modest, understanding how clinical and biologic factors interact with the MLD-RILT relationship represents a novel framework for understanding and investigating the multiple factors contributing to radiation-induced toxicity.
KW - Biomarker
KW - Cytokine
KW - Lung toxicity
KW - Non-small-cell lung cancer
KW - Radiotherapy
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U2 - 10.1016/j.radonc.2017.09.005
DO - 10.1016/j.radonc.2017.09.005
M3 - Article
C2 - 28947099
AN - SCOPUS:85029756714
SN - 0167-8140
VL - 125
SP - 66
EP - 72
JO - Radiotherapy and Oncology
JF - Radiotherapy and Oncology
IS - 1
ER -