Study of tumor control probability by stereotactic body radiotherapy with first-generation EGFR-TKIs

Our previous study suggested that patients with advanced epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma treated with first-generation EGFR tyrosine kinase inhibitors (EGFR-TKIs) followed by standard-dose stereotactic body radiotherapy (SBRT) had a larger area of computed tomography (CT)-detected radiation-induced lung injury. Radiotherapy-related lung injury remains a clinically relevant dose-limiting toxicity in thoracic SBRT. This study evaluated clinical outcomes after dose-reduced SBRT following first-generation EGFR-TKI therapy in this population. Patients with advanced EGFR-mutant lung adenocarcinoma treated with first-generation EGFR-TKI therapy combined by SBRT to the primary lung tumor between September 2016 and December 2022 were retrospectively included. Clinical outcomes after standard-dose SBRT (50–60 Gy in 5–8 fractions) were compared with those after dose-reduced SBRT (40–48 Gy in 5–8 fractions), including one-year local control rate (LCR), progression-free survival (PFS), overall survival (OS), and radiation pneumonitis (RP). Tumor control probability (TCP) modeling based on one-year LCR was performed as an exploratory analysis. A total of 54 patients were included in the primary analysis: 22 in the standard-dose group and 32 in the dose-reduced group. No statistically significant differences were observed in median PFS (13.5 vs. 13.3 months, P = 0.41), median OS (24.9 vs. 28.9 months, P = 0.67), or one-year LCR (90% vs. 90%). Grade 2 RP occurred in 6 of 22 patients (27.3%) in the standard-dose group and 5 of 32 patients (15.6%) in the dose-reduced group. Exploratory TCP modeling estimated the 50% tumor control dose (TCD 50 ) as 50 Gy for the EGFR-TKI plus SBRT cohort and 61.9 Gy for the SBRT-alone reference cohort. In patients with advanced EGFR-mutant lung adenocarcinoma receiving first-generation EGFR-TKI therapy combined by SBRT, the protocol-defined 20% dose-reduced SBRT regimen yielded observed local tumor control comparable to that of standard-dose SBRT, with no statistically significant differences in PFS or OS and a numerically lower incidence of grade 2 RP.