P3-205: Long-term results of adjuvant radiotherapy in patients with resected non small cell lung cancer

Abstract

Purpose: To investigate,prospectively,clinical,physical parameters and changes in serum interleukin-1α(IL-1α), IL-1β, IL-6,IL-7, tumor necrosis factor-α (TNF-α), transforming growth factor-β1(TGF-β1) and manganese superoxide dismutase (MnSOD) as indicators for CT-CAE3.0 ≥Grade2 pulmonary fibrosis induced by neoadjuvant platinumbased chemotherapy and thoracic radiotherapy(TRT). Methods: Between January and December 2004, 86 patients (66 with lung cancer,10 esophageal cancer, 5 malignant thymoma, 5 mediastinum tumor) who received incidental thoracic irradiation and neoadjuvant platinum-based chemotherapy were enrolled in this prospective study. There were 9 females and 77 males(median age, 57 years; range, 19-74). The median follow-up was 96 days (range, 30-557). All patients received neoadjuvant platinum-based chemotherapy. Chemo-regimen included NP, NIP, EP, IEP and CAP. The medium pre-RT cycle was one (range, 1-6). Radiation dose ranged 30-66Gy.Cad-plan™v6.08 and Pinnacle 3 ™v7.0 treatment planning system were applied to generate dosimetric metrics as following: mean lung dose(MLD),V 10 to V 60 in 10Gy increments. Serial serum concentration of IL-1α, IL-1β, IL-6, IL-7, TNF-α, TGF-β1 and MnSOD were determined by enzymelinked immunosorbent assay (ELISA) prior to and weekly during RT. Since great inter-patient divergence was revealed for baseline serum cytokines and MnSOD levels,we calculated week1/pre-RT ratios (w1/0 ratio, defined as serum concentration in the 1 st week of RT/Pre-RT level) as surrogates.On univariate analysis,various dosimetric,serum cytokines,serum MnSOD,smoking history(<20 pack-year vs.≥20 pack-year) and clinical parameters (conventional RT vs.non-conventional RT, age) were studied. Hazard ratios(HRs) were estimated by Cox proportional hazard models for indicators to CTCAE3.0 Grade≥2 pulmonary fibrosis. Results: Six of 86(7%) patients developed CTCAE3.0 Grade≥2 pulmonary fibrosis. Two developed Grade2 fibrosis (proportion of total lung volume that is fibrotic is 25-<50%), 2 Grade3 (50-<75%), 2 Grade4 (≥75% or honeycombing) and 0 Grade5 (death). On univariate analysis, no single parameter significantly correlated with severe pulmonary fibrosis.IL-7 w1/0 ratio approached marginal statistical significance (p=0.06). On multivariate analysis,baseline FEV1(p=0.0352, HR 0.062) was significantly associated with ≥Grade2 pulmonary fibrosis. A trend towards significant correlation with fibrosis was observed for IL-1β w1/0 ratio and TGF-β1 w1/0 ratio,p=0.0716(HR 7.929) and p=0.0925(HR 2.561),respectively. Conclusions: Baseline FEV1 seemed to significantly associate with CTCAE3.0 Grade≥2 pulmonary fibrosis in this group of patients.IL-1β w1/0 ratio and TGF-β1 w1/0 ratio were meanwhile marginally significant indicators. However,since only a few events were observed,care should be taken in interpreting the present findings.