Predictive factors for radiation-induced pulmonary toxicity after three-dimensional conformal chemoradiation in locally advanced non-small-cell lung cancer

Abstract

Radiation pneumonitis (RP) is a restricting complication of non-small-cell lung cancer irradiation. Three-dimensional conformal radiotherapy (3D-CRT) represents an advance because exposure of normal tissues is minimised. This study tries to identify prognostic factors associated with severe RP. Eighty patients with stage IIIA (20%) and IIIB (80%) NSCLC treated with cisplatin- based induction chemotherapy followed by concurrent chemotherapy and hyperfractionated 3D-CRT (median dose: 72.4 Gy, range: 54.1-85.9) were retrospectively evaluated. Acute and late RP were scored using RTOG glossary. Potential predictive factors evaluated included clinical, therapeutic and dosimetric factors. The lungs were defined as a whole organ. Univariate and multivariate analyses were performed. Early and late RP grade>or=3 were observed in two patients (2%) and 10 patients (12%), respectively. Five patients (6%) died of pulmonary toxicity, 3 of whom had pre-existing chronic obstructive pulmonary disease (COPD). Median time to occurrence of late RP was 4.5 months (range: 3-8). Multivariate analysis showed that COPD (OR=10.1, p=0.01) and NTCPkwa>30% (OR=10.5, p=0.007) were independently associated with late grade>or=3 RP. Incidence of RP>or=3 grade for patients with COPD and/or NTCPkwa>30% was 25% vs. 4% for patients without COPD and NTCPkwa<30% (p=0.01). Risk of severe RP was higher for patients with COPD and/or NTCPkwa>30% (OR=7.3; CI 95%=1.4-37.3, p=0.016). COPD and NTCP are predictive of severe RP. Careful medical evaluation and meticulous treatment planning are of paramount importance to decrease the incidence of severe RP.