Outcomes of surgery and subsequent therapy for central nervous system oligoprogression in EGFR-mutated NSCLC patients

Abstract

Background: Oligoprogression is an emerging issue in patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC). However, the surgical treatment for central nervous system (CNS) oligoprogression is not widely discussed. We investigated the outcomes of craniotomy with adjuvant whole-brain radiotherapy (WBRT) and subsequent therapies for CNS oligoprogression in patients with EGFR-mutated NSCLC.

Methods: NSCLC patients with CNS oligoprogression were identified from a tertiary medical center. The outcomes of surgery with adjuvant WBRT or WBRT alone were analyzed, along with other variables. Overall survival and progression-free survival were analyzed using the log-rank test as the primary and secondary endpoints. A COX regression model was used to identify the possible prognostic factors.

Results: Thirty-seven patients with CNS oligoprogression who underwent surgery or WBRT were included in the study after reviewing 728 patients. Twenty-one patients underwent surgery with adjuvant WBRT, and 16 received WBRT alone. The median overall survival for surgery and WBRT alone groups was 43 (95% CI 17-69) and 22 (95% CI 15-29) months, respectively. Female sex was a positive prognostic factor for overall survival (OR 0.19, 95% CI 0.06-0.57). Patients who continued previous tyrosine kinase inhibitors (OR 3.48, 95% CI 1.06-11.4) and induced oligoprogression (OR 3.35, 95% CI 1.18-9.52) were associated with worse overall survival. Smoking history (OR 4.27, 95% CI 1.54-11.8) and induced oligoprogression (OR 5.53, 95% CI 2.1-14.7) were associated with worse progression-free survival.

Conclusions: Surgery combined with adjuvant WBRT is a feasible treatment modality for CNS oligoprogression in patients with EGFR-mutated NSCLC. Changing the systemic-targeted therapy after local treatments may be associated with improved overall survival.

Keywords: Metastasis; Metastatic brain tumors; Non-small cell lung cancer; Oligometastasis; Oligoprogression; Tyrosine kinase inhibitor.

Fig. 1

Diaphragm of patient selection. NSCLC, non-small cell lung cancer; EGFR, epidermal growth factor receptor; TKI, tyrosine kinase inhibitors; WBRT, whole brain radiation therapy

Fig. 2

T1-weighted gadolinium-enhanced brain MRI of a 58-year-old man. Oligoprogression lesions were found in the left occipital (A), left frontal lobe (B), and right cerebellum (C). After left occipital tumor excision and adjuvant whole-brain radiotherapy, the patient changed from afatinib to osimertinib. Lesions were controlled well after a 6-month image follow-up (D, E, F)

Fig. 3

T1-weighted gadolinium-enhanced brain MRI of a 64-year-old man. Olioprogression lesions were noted in left occipital lobe (A), right basal ganglia (B), and left cerebellum (C). The patient continued afatinib after surgically removing the left occipital tumor with adjuvant WBRT. After a 6-month follow-up, the tumor was controlled in the left occipital (D) but progressed in the right basal ganglia (E) and left cerebellum (F)

Fig. 4

The Kaplan–Meier survival curve for different variables, including local therapies (A), genders (B), Karnofsky performance scale (KPS) (C), and different oligoprogression types (D) in patients with NSCLC central nervous system oligoprogression

Fig. 5

The Kaplan–Meier survival curve of overall survival (A), progression-free survival (B), and overall survival for T790M negative patients who received different subsequent therapies (C) in NSCLC central nervous system oligoprogessive disease. *p value done by Breslow method