Results of a Single Institution Experience with Dose-Escalated Chemoradiation for Locally Advanced Unresectable Non-Small Cell Lung Cancer

BACKGROUND: We determined factors associated with morbidity and outcomes of a series of non-small cell lung cancer (NSCLC) patients treated with dose-escalated chemoradiotherapy at the University of Pittsburgh Lung Cancer Program. METHODS AND MATERIALS: The records of 170 stage III NSCLC patients treated with definitive intent were retrospectively reviewed. All patients received four-dimensional CT simulation scan and had respiratory gating if tumor movement exceeded 5 mm. Overall survival (OS), locoregional control (LRC), and freedom from distant metastasis (FFDM) were calculated using log-rank and Cox regression analysis. RESULTS: For the present series of patients, median follow-up was 36.6 months, median survival 27.4 months, and the 2- and 4-year OS was 56.0 and 30.7%, respectively. The 4-year LRC and FFDM were 43.9 and 40.7%, respectively. No benefit was associated with irradiation doses above 66 Gy in OS (p = 0.586), LRC (p = 0.440), or FFDM (p = 0.230). On univariate analysis, variables associated with worse survival included: clinical stage IIIB (p = 0.037), planning target volume (PTV) over 450 cc (p < 0.001), heart V(30) over 40% (p = −0.048), and esophageal mean dose over 20% (p = 0.024), V(5) (p = −0.015), and V(60) (p = −0.011). On multivariable analysis, PTV above 450 cc (52.2 vs. 25.3 months, p < 0.001) and esophageal V(60) >20% (43.8 vs. 21.3 months, p = −0.01) were associated with lower survival. Grade 2 or higher acute lung toxicity and esophagitis were detected in 9.5 and 59.7%, respectively of patients. Grade 2 or higher acute lung toxicity was reduced if lung V(5) was ≤65 (7.4 vs. 23.8%, p = 0.03). Grade 2 or higher acute esophagitis was reduced if V(60) ≤ 20% (62 vs. 81.3%, p = 0.018). The use of intensity-modulated radiation therapy was more frequent in stage IIIB compared to stage IIIA patients (56.5 vs. 39.5%, p = 0.048) and was associated with a higher lung V(5) and V(10). CONCLUSION: The outcomes of a program of dose-escalated chemoradiotherapy for unresectable stage IIIA and IIIB NSCLC patients were consistent with other studies and showed no benefit to radiation doses above 66 Gy. Furthermore, maintaining low esophageal V(60) and lung V(5) were associated with lower morbidity and mortality.