Acute toxicities followed by management of locally advanced nonsmall cell lung cancer – TGF-B1 as a predictor

Background and purpose

Regionally advanced non-small cell lung cancer represents a disease with an extremely poor prognosis. Radiochemotherapy is an effective treatment for locally advanced NSCLC. This management can be limited by acute and late toxicities, especially esophagitis and pneumonitis. Transforming growth factor beta 1 (TGF-B1) could be used to predict patients at risk for the development of radiation pneumonitis.

Patients and methods

Between 2000 and 2005, a total of 30 patients with locally advanced non-small cell lung cancer stage IIIA and IIIB were treated. Neoadjuvant (4 cycles) and concurrent (2 cycles) radiochemotherapy consisted of paclitaxel 175 mg/m² i.v. infusion and cisplatin 75 mg/m² i.v. infusion was administred every 3 weeks in group A (n=15) and group B (n=15). During concurrent radiochemotherapy was administred amifostine i.v. infusion 500 mg daily only in group A. All patients were treated using 3D conformal radiotherapy (3D-CRT) with planning doses to the ICRU reference point ranging from 63.8 to 72.8 Gy. All patients were assessed at each follow-up visit for signs and symptoms of pneumonitis according to Common Toxicity Criteria, version 2.0. Changes in plasma TGF-B1 levels were obtained before CT, before RT, in the middle of course RT, and after RT.

Results

Radiation pneumonitis grade 1/2 occurred in 10 patients in group A vs 6 patients in group B. Radiation pneumonitis grade 3/4 occurred in 5 patients in group A vs 9 patients in group B. Plasma level TGF-B1 were statistically signifi cant elevated (p=0.001) in the middle of course RT in group A (14.9 ng/ml) vs group B (31.3 ng/ml), respectively. Mean gross tumor volume (GTV) and planning target volum 2 (PTV2) were 166.13 cm3 (63.40-284.26) and 283.6 cm3 (183.2-366.4), respectively. Median 3D-CRT dose was 67.4 Gy (63.8-72.8 Gy).

Conclusions

The incidence of radiation pneumonitis was lower for patients receiving amifostine than for patients receiving radiochemotherapy alone. These results suggest that plasma TGF-B1 levels during treatment may be useful to determine which patients are at high risk of developing radiation pneumonitis.