Early Tumor and Nodal Response in Patients with Locally Advanced Non-Small Cell Lung Carcinoma Predict for Oncologic Outcomes in Patients Treated with Concurrent Proton Therapy and Chemotherapy

Purpose: There are no established imaging biomarkers that predict response during chemoradiation for patients with locally advanced non-small cell lung carcinoma. At our institution, proton therapy (PT) patients undergo repeat computed tomography (CT) simulations twice during radiation. We hypothesized that tumor regression measured on these scans would separate early and late responders and that early response would translate into better outcomes. Methods and Materials: Patients underwent CT simulations before starting PT (CT0) and between weeks 1 to 3 (CT1) and weeks 4 to 7 (CT2) of PT. Primary tumor volume (TVR) and nodal volume (NVR) reduction were calculated at CT1 and CT2. Based on recursive partitioning analysis, early response at CT1 and CT2 was defined as ≥20% and ≥40%, respectively. Locoregional and overall progression-free survival (PFS), distant metastasis–free survival, and overall survival by response status were measured using Kaplan–Meier analysis. Results: Ninety-seven patients with locally advanced non-small cell lung carcinoma underwent definitive PT to a median dose of 66.6 Gy with concurrent chemotherapy. Median TVR and NVR at CT1 were 19% (0-79%) and 19% (0-75%), respectively. At CT2, they were 33% (2-98%) and 35% (0-89%), respectively. With a median follow-up of 25 months, the median overall survival and PFS for the entire cohort was 24.9 and 13.2 months, respectively. Compared with patients with TVR and NVR <20% at T1 and <40% at T2, patients with TVR and NVR ≥20% at CT1 and ≥40% at CT2 had improved median locoregional PFS (27.15 vs 12.97 months for TVR ≥40% vs <40%, P < .01, and 25.67 vs 12.09 months for NVR ≥40% vs <40%, P < .01) and median PFS (22.7 vs 9.2 months, P < .01, and 20.3 vs 7.9 months, P < .01), confirmed on multivariate Cox regression analysis. Conclusions: Significantly improved outcomes in patients with early responses to therapy, as measured by TVR and NVR, were seen. Further study is warranted to determine whether treatment intensification will improve outcomes in slow-responding patients.