Positron Emission Tomography–Adjusted Intensity Modulated Radiation Therapy for Locally Advanced Non-Small Cell Lung Cancer

Purpose: To perform a prospective trial examining positron emission tomography (PET)-based, dose-painted intensity modulated radiation therapy (IMRT) in the setting of locally advanced non-small cell lung cancer (NSCLC). Methods and Materials: Patients with stage IIB-III NSCLC were treated with 25 fractions of dose-painted IMRT. Tumors or lymph nodes with metabolic tumor volume exceeding 25 cm³ were deemed “high risk” and received 65 Gy. Smaller lesions were treated with 57 Gy or 52.5 Gy (after November 2014). Patients received concurrent weekly carboplatin (area under the curve = 2) and paclitaxel (45 mg/m²). The primary study endpoint was the absence of high residual metabolic activity (maximum standardized uptake value > 6) in treated lesions on PET 12 to 16 weeks after completion of IMRT. Results: Thirty-five subjects with 116 hypermetabolic lesions were eligible for analysis. The primary endpoint was met for 24 of 30 patients (80%) who underwent posttreatment PET, satisfying our efficacy objective. With a median follow-up duration of 23.8 months for living patients, progression in a lesion targeted with radiation therapy has been observed in 5 patients (14%). Treating progression in other sites and death without progression as competing risks, 2-year cumulative incidence rates of local disease progression in high-risk lesions (n=24) and low-risk lesions (n=92) are 9% and 3%, respectively. The actuarial rate of overall survival at 2 years is 52%. Conclusions: Dose-painted IMRT based on pretreatment PET metrics with concurrent chemotherapy yields high rates of metabolic response and local disease control for locally advanced NSCLC. Future trials should test this approach to maximize the therapeutic ratio of thoracic radiation therapy.