Radiation pneumonitis and early circulatory cytokine markers

Chen, Yuhchyau; Williams, Jacqueline P.; Ding, Ivan; Hernady, Eric; Liu, Weimin; Smudzin, T.; Finkelstein, Jacob N.; Rubin, Philip; Okunieff, Paul

doi:10.1053/srao.2002.31360

Cited by 216 publications

(126 citation statements)

References 27 publications

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“…Inflammatory cytokines have been implicated in the development and perpetuation of post-irradiation injury in various tissues, including the lung [27]. Serum levels of cytokines, in particular, interleukin-6 (IL-6) and transforming growth factor-β (TGF-β), are inconclusive in predicting radiation pneumonitis [28][29][30][31][32]. To what extent such changes are a direct result of radiation as opposed to a consequence of up-regulation of other cytokines and chemokines remains to be established [33,34].…”

Section: Discussionmentioning

confidence: 99%

High superoxide dismutase and low glutathione peroxidase activities in red blood cells predict susceptibility of lung cancer patients to radiation pneumonitis

Park

Ramnath

Yang

et al. 2007

Free Radical Biology and Medicine

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Radiation pneumonitis is an unpredictable complication of radiotherapy for lung cancer and a condition which can cause significant morbidity. The ability to identify patients at a high risk of developing pneumonitis is critical, since it will enable the individualization of the treatment plan. Because the cytotoxic effect of radiation is propagated through ROS and ROS-driven oxidative stress, the role of anti-oxidant defense systems in radiation pneumonitis was investigated. Using the pneumonitis-sensitive C3H/HeN mice as a model, we demonstrated that the anti-oxidant response of the lung correlated well with that of RBC. We then proceeded to test whether differences of RBC anti-oxidant response would predict the pneumonitis development in patients. SOD, GPX, CAT activities and glutathione in RBC were measured at baseline and then weekly for 6 weeks of treatment in fifteen eligible patients receiving concurrent chemo-radiotherapy for unresectable stage III NSCLC. Striking differences were found in the anti-oxidant activities of RBC with respect to the pneumonitis development. Those who developed pneumonitis showed higher SOD and lower GPX activities at baseline compared to those who did not (3.7 vs. 6.8 unit/mg for median SOD, 16.5 vs. 10.7 nmol/min/mg for median GPX). The functional imbalance of SOD and GPX was displayed consistently throughout the treatment period. The sensitivity and specificity of pneumonitis prediction were further increased when the GPX/SOD ratio was analyzed (pre-treatment P = 0.0046). Our results provide a strong rationale to monitor SOD and GPX activities of RBC to identify patients who are at risk of developing pneumonitis, and to implement a strategy of increasing the GPX/SOD ratio in order to lower the risk.

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Section: Discussionmentioning

confidence: 99%

High superoxide dismutase and low glutathione peroxidase activities in red blood cells predict susceptibility of lung cancer patients to radiation pneumonitis

Park

Ramnath

Yang

et al. 2007

Free Radical Biology and Medicine

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“…The mechanisms through which TGF-β1 performs are complex, and involve both the inhibition of epithelial cell proliferation and the development of tissue fibrosis in response to irradiation [3,15,[29][30][31]. The role of TGF-β1 in the progression of human disease and in tissue response to therapy has already been described in great detail [3,7,[12][13][14][15][16][17][18]20,22,[32][33][34].…”

Section: Discussionmentioning

confidence: 99%

“…In studies from the University of Rochester, Chen et al [33] suggested that interleukin 1α (IL-1α) and interleukin 6 (IL-6) might also be predictive for RP. The production of cytokines (TGF-β1, among others) that occurs in the tumor may be affected by treatment.…”

Section: Discussionmentioning

confidence: 99%

Does transforming growth factor-β1 predict for radiation-induced pneumonitis in patients treated for lung cancer?

et al. 2006

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The purpose of the study was to reassess the utility of transforming growth factor-beta-1 (TGF-β1) together with dosimetric and tumor parameters as a predictor for radiation pneumonitis (RP). Of the 121 patients studied, 32 (26.4%) developed grade ≥ 1 RP, and 27 (22.3%) developed grade ≥ 2 RP. For the endpoint of grade ≥ 1 RP, those with V30 > 30% and an end-RT/baseline TGF-β1 ratio ≥ 1 had a significantly higher incidence of RP than did those with V30 > 30% and an end-RT/baseline TGF-β1 ratio < 1. For most other patient groups, there were no clear associations between TGF-β1 values and rates of RP. These findings suggest that TGF-β1 is generally not predictive for RP except for the group of patients with a high V30.

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“…Other studied have correlated serum inflammatory biomarkers with RP symptoms. [6][7][8] Whereas the volume of lung irradiated can be accurately determined from the radiation treatment plan, the individual inflammation response cannot be readily measured at the time of clinical symptoms. Because outliers in response to thoracic radiotherapy are often present, such as the case of fatal RP in Graham's data 9 with a V20 (percentage of lung volume that received > 20 Gy) of only 22%, an objective measure of pulmonary radiation response is needed.…”

Section: Introductionmentioning

confidence: 99%

Radiation Pneumonitis: Correlation of Toxicity With Pulmonary Metabolic Radiation Response

Hart

McCurdy

Ezhil

et al. 2008

International Journal of Radiation Oncology*Biology*Physics

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Purpose-To characterize the relationship between radiation pneumonitis (RP) clinical symptoms and pulmonary metabolic activity on post-treatment [ 18 F]-fluorodeoxyglucose positron emission tomography (FDG PET).Methods-We retrospectively studied 101 esophageal cancer patients who underwent restaging FDG PET/CT imaging between 3 and 12 weeks after completing thoracic radiotherapy. The Common Toxicity Criteria version 3 (CTC3) was used to score RP clinical symptoms. Linear regression was applied to the FDG PET/CT images to determine the normalized FDG uptake versus radiation dose. The pulmonary metabolic radiation response (PMRR) was quantified as this slope. Modeling was performed to determine the interaction of PMRR, mean lung dose (MLD), and percentage of lung receiving greater than 20 Gy (V20) with RP outcomes.Results-Of the 101 patients, 25 had grade 0, 10 had grade 1, 60 had grade 2, 5 had grade 3, and 1 had grade 5 RP symptoms. Logistic regression demonstrated that increased values of both MLD and PMRR were associated with a higher probability of RP clinical symptoms (P=0.032 and P=0.033, respectively). Spearman's rank correlation found no association between the PMRR and dosimetric parameters (PTV, MLD, V5 through V30). Two-fold cross validation demonstrated the combination of MLD and PMRR was superior to either alone for assessing the development of Conflict of Interest Notification:The authors declare that they have no commercial or financial interests related to this study to disclose.Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Conclusions-This study demonstrated a significant correlation between RP clinical symptoms and the PMRR measured by FDG PET/CT following thoracic radiotherapy. NIH Public Access

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Radiation pneumonitis and early circulatory cytokine markers

Cited by 216 publications

References 27 publications

High superoxide dismutase and low glutathione peroxidase activities in red blood cells predict susceptibility of lung cancer patients to radiation pneumonitis

High superoxide dismutase and low glutathione peroxidase activities in red blood cells predict susceptibility of lung cancer patients to radiation pneumonitis

Does transforming growth factor-β1 predict for radiation-induced pneumonitis in patients treated for lung cancer?

Radiation Pneumonitis: Correlation of Toxicity With Pulmonary Metabolic Radiation Response

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