Results of a Single Institution Experience with Dose-Escalated Chemoradiation for Locally Advanced Unresectable...

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.

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.

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 V₃₀ over 40% (p = -0.048), and esophageal mean dose over 20% (p = 0.024), V₅ (p = -0.015), and V₆₀ (p = -0.011). On multivariable analysis, PTV above 450 cc (52.2 vs. 25.3 months, p < 0.001) and esophageal V₆₀ >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 V₅ was ≤65 (7.4 vs. 23.8%, p = 0.03). Grade 2 or higher acute esophagitis was reduced if V₆₀ ≤ 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 V₅ and V₁₀.

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 V₆₀ and lung V₅ were associated with lower morbidity and mortality.