Impact of EGFR Mutational Status on SBRT Lung Oligometastatic Tumor Response

Summary: Purpose/Objective(s): Epidermal growth factor receptor (EGFR) mutations in lung cancer are the most common driver mutations in non-small cell lung cancer (NSCLC). Many patients with EGFR-mutated NSCLC have oligometastatic disease that is amenable to treatment with SBRT while maintaining systemic targeted therapy (i.e. with tyrosine kinase inhibitors, or TKIs). In preclinical studies, there is a described radiosensitivity difference between EGFR mutant and wild-type NSCLC, but the clinical imaging impact of radiosensitivity is not well understood. Therefore, our study aims to find any association between the EGFR mutation (with or without concurrent TKI administration) and CT-based tumor response to lung SBRT. Materials/Methods: We examined a consecutively treated cohort of lung adenocarcinoma patients with or without EGFR mutations, from our IRB-approved lung SBRT registry, who developed oligoprogression that was treated with definitive dose SBRT. Pre-treatment CT and post-treatment CTs at 3 and 12 months after treatment completion were reviewed, maximal tumor dimensions were measured, and percent changes were calculated between each timepoint. Also, TKI therapy in the presence of SBRT was reviewed. Results: Overall 24 patients were evaluated. Twelve patients had EGFR mutations and 10/12 patients were on TKI’s. Compared to pretreatment scans, there was a 97% mean reduction in tumor size in the EGFR-mutated cohort compared with 118% decrease for non-EGFR mutated cohort at 3 months. Compared to pretreatment scans and 12-month post treatment, there was a mean reduction in the tumor size by 104% in EGFR-mutated cohort versus 135% mean reduction for non-EGFR mutated cohort. There was a mean reduction of 149% in tumor size between the 3-month and 12-month scans for the EGFR mutated cohort compared with 155% mean reduction in non-EGFR mutated cohort. Two patients from the EGFR-mutated cohort were not on TKI’s. When compared to similar EGFR-mutated patients on TKI’s, the non-TKI EGFR-mutated cohort had 115% and 116% mean reduction in tumor size at 3 months and 12 months respectively. The EGFR-mutated cohort on TKI’s had 43% and 59% mean reduction in tumor size at 3 months and 12 months respectively Conclusion: Numerically (based on raw data), there was a higher initial mean reduction in tumor size in the non-EGFR mutated cohort compared to the EGFR mutated cohort, and a similar 3 to 12-month tumor size reduction between the two groups. There may be early inflammatory changes immediately after SBRT in the EGFR mutated group that obscure/augment true tumor size, for which metabolic Positron Emission Tomography (PET) assessment may be more meaningful in future study. Further investigation with a larger patient population is needed to better characterize these inflammatory imaging changes as they may relate to radiosensitivity conferred by EGFR mutations and/or concurrent TKI administration