TGF-beta, radiation-induced pulmonary injury and lung cancer

To determine whether changes in TGF-beta plasma levels during radiation therapy may be useful in predicting radiation-induced pulmonary injury and tumour response in non-small-cell lung cancer (NSCLC) patients.

Plasma TGF-beta was investigated in 27 patients with stage III NSCLC, who were treated with 60 Gy (2Gy/day) radiotherapy with or without carboplatin. TGF-beta was measured prior to beginning radiotherapy and weekly during treatment; evaluated as a ratio between TGF-beta levels obtained during treatment and the pretreatment TGF-beta level. The endpoints of the study were development of symptomatic radiation pneumonitis and tumour response.

Nine of the 27 patients developed pneumonitis. The patients who developed pneumonitis had high persistent TGF-beta levels throughout the course of treatment (TGF-beta ratio>1), whereas the TGF-beta levels in patients who did not develop pneumonitis were unchanged or declined towards normal (TGF-beta ratio < 1). Patients who responded to treatment had low or normal TGF-beta levels during treatment compared with patients who failed to respond. Other parameters such as pretreatment TGF-beta values, carboplatin treatment or field size did not appear to have a significant effect, which is probably due to the small number of patients entered in the study.

This pilot study, with a limited number of patients, suggests the hypothesis that elevated TGF-beta levels during radiotherapy may not only indicate patients with a higher risk of developing pulmonary toxicity but also patients with a higher risk of treatment failure. This remains to be tested in a larger clinical study.