A Phase 2 Trial of Primary Tumor Stereotactic Body Radiation Therapy Boost Before Concurrent Chemoradiation for Locally Advanced Non-Small Cell Lung Cancer

ABSTRACT

BACKGROUND

Primary tumor failure is common in patients treated with chemoradiation (CRT) for locally-advanced NSCLC (LA-NSCLC). Stereotactic body radiation therapy (SBRT) yields high rates of primary tumor control (PTC) in early-stage NSCLC. This trial tested an SBRT boost to the primary tumor prior to the start of CRT to improve PTC.

MATERIALS/METHODS

Patients with LA-NSCLC received an SBRT boost in 2 fractions (central location 12 Gy, peripheral location 16 Gy) to the primary tumor, followed by standard CRT (60 Gy in 30 fractions). The primary objective was PTC rate at 1-year with a hypothesis that the 1-year PTC rate is ≥90%. Secondary objectives included objective response rate (ORR), regional & distant control, disease-free survival (DFS), and overall survival (OS). Correlative studies included functional MRI (fMRI) and blood-based miRNA analysis.

RESULTS

The study enrolled 21 patients (10 male, 11 female), with median age 62 years (range 52-78). Median pre-treatment primary tumor size was 5.0 cm (range 1.0-8.3). The most common non-hematologic toxicities were pneumonitis, fatigue, esophagitis/dysphagia, dyspnea, and cough. Only 1 treatment-related grade 4 non-hematologic toxicity occurred (respiratory failure/radiation pneumonitis), and there were no grade 5 toxicities. ORR at 3 and 6 months was 72.7% and 80.0%, and PTC at 1 and 2 years was 100% and 92.3%, respectively. The 2-year regional and distant control were 81.6% and 70.3%, respectively. DFS and OS at 2 yrs were 46.1% and 50.3%, respectively. Median survival was 37.8 months. fMRI detected a mean relative decrease in BOLD signal of -87.1% (p=0.05), and miR.142.3p correlated with increased risk of grade≥3 pulmonary toxicity (p=0.01).

CONCLUSIONS

Dose escalation to the primary tumor utilizing upfront SBRT appears feasible and safe. PTC was high and other oncologic endpoints compared favorably to standard treatment. fMRI suggested changes in oxygenation with the first SBRT boost dose, and miR.142.3p correlated with pulmonary toxicity.