CHANGES IN PLASMA TGF-BETA LEVELS DURING PULMONARY RADIOTHERAPY AS A PREDICTOR OF THE RISK OF DEVELOPING RADIATION PNEUMONITIS

Purpose: To determine whether plasma transforming growth factor-beta ( TGF-beta) levels measured before and during radical radiotherapy for l ung cancer could be used to predict patients at risk for the developme nt of radiation pneumonitis. Methods and Materials: The first eight pa tients with lung cancer (nonsmall cell: seven, small cell: one) enroll ed in a prospective study designed to evaluate physiological and molec ular biologic correlates of radiation induced normal tissue injury are described. The study began in June 1991. All patients were treated wi th radiotherapy with curative intent. Plasma transforming growth facto r beta levels were obtained before, weekly during, and at each follow- up after treatment. Pretreatment pulmonary function tests and single p hoton emission computed tomography scans were obtained to assess basel ine lung function and were repeated at follow-up visits. Dose-volume h istogram analyses were performed to determine the volume of lung which received greater than or equal to 30 Gy. Patients were assessed at ea ch follow-up visit for signs and symptoms of pneumonitis. Results: Fiv e patients developed signs and/or symptoms of pulmonary injury consist ent with pneumonitis and three patients did not. In all three patients not developing pneumonitis, plasma TGF-beta levels normalized by the end of radiotherapy. In contrast, four out of five patients who suffer ed pneumonitis had persistently elevated plasma TGF-beta levels by the end of therapy. This finding appeared to be independent of the volume of irradiated lung. Conclusions: These results suggest that plasma TG F-beta levels during treatment may be useful to determine which patien ts are at high risk of developing symptomatic pneumonitis following th oracic radiotherapy. This finding may have implications when planning additional therapy (either chemotherapy or radiotherapy) which may hav e potentially adverse consequences on the lung.