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Journal of Thoracic Oncology:
doi: 10.1097/01.JTO.0000283349.07248.6b
Poster Discussion Abstracts: Session PD2: Tuesday, September 4, Cancer Genetics and Tumor Biology: Cancer Genetics and Tumor Biology, Tue, 16:00 - 17:30

Changes in plasma levels of cytokines during fractionated radiotherapy of non-small cell lung cancer (NSCLC): the relation with metabolic response and toxicity: PD2-1-3

van Baardwijk, Angela1; Bosmans, Geert1; Boersma, Liesbeth1; Wanders, Rinus1; Vernooy, Juanita2; Mandic Havelka, Aleksandra3; Lambin, Philippe1; Cohen-Tervaert, Jan-Willem4; De Ruysscher, Dirk1

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1Dept. of Radiation Oncology (MAASTRO), GROW Research Institute, University Hospital Maastricht, Maastricht, The Netherlands 2Dept. of Respiratory Medicine, Nutrition and Toxicology Research Institute Maastricht, University of Maastricht, Maastricht, The Netherlands 3Cancer Center Karolinska, Karolinska Hospital and Institute, Stockholm, Sweden 4Dept. of Clinical and Experimental Immunology, University Hospital Maastricht, Maastricht, The Netherlands

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Background:

Radiation dose escalation might improve local control in NSCLC, but is associated with increased toxicity. Consequently patients have to be selected carefully to prevent, both over- and undertreatment. As part of a prospective clinical trial we reported that metabolic responders and non-responders (EORTC-criteria) showed different time trends in maximal SUV (standardized uptake value, SUVmax) of 18F-FDG on PET-scan. Moreover, metabolic responders showed an improved overall survival compared to non-responders (van Baardwijk et al., Radioth Oncol 2007). The aim of the current study was to investigate changes in plasma levels of cytokines and the association of these changes with SUVmax and the amount of toxicity during and after radiotherapy (RT), to further unravel underlying mechanisms.

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Methods:

From 21 patients included in the clinical trial, repeated plasma samples (n=67) were collected before RT, on day 7 and 14 during RT and 70 days after RT. Levels of IL-1b, IL-5, IL-6, IL-8, IL-10, TNF-α, M30, M65, osteopontin and neopterin were assessed using ELISA’s. Unmeasurable levels were assumed to be zero. Levels of cytokines were associated with SUVmax of FDG-PET and toxicity score, according to CTCAE-criteria. Moreover, changes in levels of cytokines between the different time points during RT (day 0 versus day 7, day 7 versus day 14) were correlated with changes in SUVmax within the same time-interval. Results are expressed as mean ± SEM. Pearson correlation coefficient and Mann Whitney U-test were used to analyze the data.

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Results:

A large heterogeneity in evolution in cytokine levels during RT was observed between individual patients. It was shown that changes in SUVmax correlated with changes in the level of IL-6, showing a correlation coefficient of 0.51 for the change between day 0 and day 7 (p=0.02) and of 0.59 for the change in the second week of RT (day 7 and 14, p=0.02). This correlation was not observed for other cytokines. Moreover, IL-6 levels were higher in patients showing no metabolic response compared to responders: day 0 resp. 18.9 ± 7.6 and 6.0 ± 0.9 (p=0.06), day 7 resp. 31.0 ± 13.0 and 9.5 ± 3.0 (p=0.03) and for day 14 resp. 25.3 ± 12.2 and 8.5 ± 1.9 (p=0.10). Seventy days after RT, levels of IL-1b (r=-0.55, p=0.04) as well as neopterin (r=0.58, p=0.04) were positively correlated with clinically symptomatic pneumonitis (>grade 1). Furthermore, the dyspnea score at this time point showed a graded correlation with plasma levels of neopterin (r=0.76, p≤0.01) and the cough score with osteopontin levels (r=0.81, p≤0.01), while these phenomena were not observed during RT.

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Conclusions:

Changes in SUVmax were positively correlated with changes in IL-6 levels during radiotherapy, suggesting that changes in FDG uptake might be partly explained by inflammation. Seventy days after radiotherapy, levels of neopterin were correlated with both symptomatic pneumonitis and dyspnea score, assuming cell-mediated immune activation in the development of pneumonitis. Furthermore, levels of osteopontin, a lungfibrosis related protein, were correlated with cough score after radiotherapy.

Copyright © 2007 by the European Lung Cancer Conference and the International Association for the Study of Lung Cancer.

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