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Early Variations of Circulating Interleukin-6 and Interleukin-10 Levels During Thoracic Radiotherapy Are Predictive for Radiation Pneumonitis

From the Department of Pneumology, Hôpital de la Croix Rousse; Departments of Public Health (Department of Public Health—Biostatistics Unit) and Radiation Oncology and Cytokines and Cancer Research Unit Institut National de la Santé et de la Recherche Médicale U.590, Centre Léon Bérard; Department of Pneumology, Hôpital St Joseph; and Department of Pneumology, Hôpital Louis Pradel, Lyon; Department of Pneumology, Hôpital de Villefranche sur Saône, Villefranche sur Saône, France; and Blokhin Cancer Research Center, Moscow, Russia

Address reprint requests to Dominique Arpin, MD, Hôpital de la Croix Rousse, 103 Grande Rue de la Croix Rousse, 69317 Lyon Cedex 04, France; e-mail: dominique.arpin{at}chu-lyon.fr

PURPOSE: To investigate variations of circulating serum levels of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF), and interleukin-10 (IL-10) during three-dimensional conformal radiation therapy (3D-CRT) in patients with non–small-cell lung cancer and correlate these variations with the occurrence of radiation pneumonitis.

PATIENTS AND METHODS: Ninety-six patients receiving 3D-CRT for stage I to III disease were evaluated prospectively. Circulating cytokine levels were determined before, every 2 weeks during, and at the end of treatment. Radiation pneumonitis was evaluated prospectively between 6 and 8 weeks after 3D-CRT. The predictive value of clinical, dosimetric, and biologic (cytokine levels) factors was evaluated both in univariate and multivariate analyses.

RESULTS: Forty patients (44%) experienced score 1 or more radiation pneumonitis. No association was found between baseline cytokine levels and the risk of radiation pneumonitis. In the whole population, mean levels of TNF, IL-6, and IL-10 remained stable during radiotherapy. IL-6 levels were significantly higher (P = .047) during 3D-CRT in patients with radiation pneumonitis. In the multivariate analysis, covariations of IL-6 and IL-10 levels during the first 2 weeks of 3D-CRT were evidenced as independently predictive of radiation pneumonitis in this series (P = .011).

CONCLUSION: Early variations of circulating IL-6 and IL-10 levels during 3D-CRT are significantly associated with the risk of radiation pneumonitis. Variations of circulating IL-6 and IL-10 levels during 3D-CRT may serve as independent predictive factors for this complication.

Supported by grants from the French Ministry of Health (PHRC No. 2701), La Ligue Contre le Cancer de l'Ain (France), and La Ligue Contre le Cancer du Rhône (France), and European Society of Medical Oncology.

Presented in part at the 40th Annual Meeting of the American Society of Clinical Oncology, June 5-8, 2004, New Orleans, LA.

D.A., D.P., J.-Y.B., and C.C. contributed equally to this work.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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