Predictive factors for late toxicity after endobronchial brachytherapy: A multivariate analysis

Purpose: To determine the predictive factors associated with hemoptysis and radiation bronchitis after endobronchial brachytherapy by univariate and multivariate analyses Methods and Materials: One hundred forty-nine patients underwent endobronchial brachytherapy and were divided into three therapeutic groups: group I: patients treated with palliative intent (n = 47); group 2: patients treated with curative intent (small endobronchial tumors without mediastinal or general dissemination: n = 73); group 3: patients also receiving external irradiation (n = 29). One hundred twelve patients had previously received external irradiation. Brachytherapy was delivered with a dose per fraction ranging from 4 to 7 Gy and a prescription point between 0.5 and 1.5 cm, usually 1 cm from the source center. Two to six fractions were delivered according to the therapeutic group and clinical situation. The influence of the following variables on the incidence of hemoptysis or radiation bronchitis was studied: age, sex, Karnofsky score, therapeutic group, histologic type, endoscopic tumor length, dose per fraction, total brachytherapy dose, total external beam irradiation dose, total dose (brachytherapy dose plus external irradiation dose), volumes of the 100% and 200% isodoses, and volumes of the 7 and 14 Gy isodoses. Results: We observed 11 hemoptyses (7.4%), 10 were lethal. All but one occurred in patients with progressive disease. Two clinical factors were significantly associated with hemoptysis by univariate analysis: palliative group (p = 0.009) and endobronchial tumor length (p = 0.004). No technical factors seem to be implicated in the occurrence of hemoptysis. Only endobronchial tumor length remained in the multivariate model (p = 0.02). Radiation bronchitis was observed in 13 cases (8.7%). By univariate analysis, a good Karnofsky score (p = 0.02), curative treatment (p = 0.02), and tumor location on trachea and main stem bronchus (p = 0.002) were significantly associated with this complication. Two technical factors were also incriminated: the total dose (p 0.04) and the 100% isodose volume (p = 0.02). By multivariate analysis, only the tumor location retained statistical significance (p = 0.009). Conclusion: Hemoptysis is most likely due to disease progression, with the bleeding being facilitated by brachytherapy. Some rare cases could be a direct complication of brachytherapy itself, particularly when tumors are located in the upper lobes. In contrast, radiation bronchitis occurred more frequently in patients with controlled disease, and was significantly influenced by tumor location and technical factors (dose and volumes treated). Technical improvements should increase the therapeutic ratio. (C) 1998 Elsevier Science Inc.