A phase II trial of mid-treatment FDG-PET adaptive, individualized radiation therapy plus concurrent chemotherapy in patients with non-small cell lung cancer (NSCLC).

7522 Background: We have found that FDG-PET response during chemoradiation for patients with NSCLC is heterogeneous and predicts outcome. We hypothesized that dose escalated treatment targeted to the FDG-avid tumor would improve local tumor control. Methods: This is a phase II trial for patients with locally advanced, inoperable/unresectable NSCLC. Conformal radiotherapy (RT) was given in 30 daily fractions. RT dose was individualized to a fixed risk of lung toxicity and adaptively escalated to the residual tumor on mid-tx FDG-PET up to a total physical dose of 86 Gy. Patients had concurrent weekly followed by consolidation carboplatin/paclitaxel. The primary endpoint was local-regional tumor control (LRTC) at 2 years. Survival was calculated from RT start. Results were compared to stage-matched patients treated during the same time period with standard RT dosing (60-66 Gy). The data are presented as median (95% CI) unless otherwise specified. Results: 42 patients were enrolled: median age 63 years (range 45-83); 28 (67%) male; 39 (93%) smokers; 39 (93%) stage III; and 45% squamous cell. The mean gross tumor volume was 154 cc (range 10-617 cc). Median physical dose reached was 84 Gy (range 63-86 Gy), equivalent to 90 Gy in 2 Gy fractions (biological effective dose 108 Gy). 8 patients (19%) had RT-induced lung toxicity and 13 (31%) grade ≥2 esophagitis. Minimum and median follow-up were 10 and 25 months, respectively. The 2-year rates of in-field LRTC, overall LRTC, and LR-PFS were 84% (63-94%), 68% (47-82%), and 43% (27-58%), respectively. 14 patients progressed: 7 (50%) first at distant sites; 5 (36%) at nodal regions; 2 (14%) at primary tumor. Median overall survival was 26 months and 2-year overall survival rate was 51% (34-65%). These results compared favorably to stage-matched patients treated with standard-dose RT [2-year overall survival 23% (8-41%)]. Conclusions: These results support our hypothesis that adapting RT by escalating dose to the FDG avid region detected mid-tx improves 2-year local-regional tumor control. Adaptive RT may also improve overall survival. RTOG 1106 is currently testing this regimen in a randomized fashion. Clinical trial information: NCT01190527.