Pattern of failure and clinical value of local therapy for oligo-recurrence in locally advanced non-small cell lung cancer after definitive chemoradiation: Impact of driver mutation status.

Abstract

Considerable differences of treatment response and pattern of failure may exist between definitive chemoradiation (CRT) treated locally advanced non-small cell lung cancer (LA-NSCLC) patients. The clinical value of additional tyrosine kinase inhibitors (TKIs) before disease recurrence and salvage local therapy after initial recurrent disease remain controversial. Consecutive LA-NSCLC patients receiving definitive CRT and having definite results about driver mutations (EGFR, ALK and ROS1) were retrospectively reviewed. Initial recurrent disease was classified as in-field recurrence, out-of-field recurrence and distant metastasis. Recurrent disease occurred only in the brain or limited to ≤3 extra-cranial organs and ≤5 extra-cranial lesions, was defined as oligo-recurrence. Progression free survival and overall survival (OS) were calculated from diagnosis to disease progression or death, and to death, respectively. OS2 was measured from initial disease recurrence to death among patients who had recurrent disease. Of the 153 enrolled patients, 39 had driver mutations and 13 received additional TKI therapy besides definitive CRT. Patients harboring driver mutations but without additional TKI therapy had a similar PFS and significantly longer OS (p=0.032) than those without driver mutations. Additional TKI therapy prolonged PFS (p=0.021) but not OS among patients with driver mutations. No significant difference of pattern of failure was observed between patient subgroups stratified by the status of driver mutations and the usage of additional TKI therapy. Furthermore, 57 of the 95 patients with initial recurrent disease developed oligo-recurrence and salvage local therapy significantly improved OS2 (p=0.01) among patients with oligo-recurrence disease. LA-NSCLC patients receiving definitive CRT generally had similar PFS and pattern of treatment failure, regardless of driver mutation status. Additional TKI therapy besides definitive CRT could prolong PFS but not OS. The majority of recurrent disease after definitive CRT belongs to oligo-recurrence and salvage local therapy may provide survival benefit.