Demographics
The study included 232 males and 247 females. The median age of the patients was 62.5 years (range: 29.2-91.3 yrs.). A total of 131 patients (27.3%) presented with 1 intracranial lesion, 306 patients(63.9%)presented with 2~10 intracranial lesions, and the other patients presented with 11~25 lesions. Extracranial metastasis was reported in 231 patients (48.2%). The median Karnofsky Performance Scale (KPS) score was 90 (range 50-100). The median imaging follow-up period was 12.3 months (range: 0.13-114 months), and the median clinical follow-up period was 12.7 months (range: 0-120.5 months). The treatment regimens were as follows: Craniotomy prior to GKRS (13.9%), WBRT (13.9%), chemotherapy (44.1%), and TKIs (70.8%). The major tumor type was pure adenocarcinoma (90.0%). Gene mutation distribution was as follows: wild-type EGFR (150 patients), ALK+ mutations (25 patients), EGFR mutations (296 patients). Most of the mutations were located at L858R (25.5%), followed by exon 19 (22.3%) and exon 20 (1.9%). Among the deceased patients, the median survival time was 10.9 months and the longest survival time was 122.3 months (Table 1).
Overall survival after GKRS
The median follow up duration time was 12.7 months. OS rates of all patients in this study (n=479) were as follows: 12 months (73.8%), 24 months (58.4%), 36 months (52.1%), and 48 months (39.9%) (Figure 1A). The 2-year survival rate in the two main groups was as follows: EGFR positive patients (62.6%) and EGFR wild-type patients (46.2%) (p = 0.0016, Figure 1B). As shown in Fig. 1C, among EGFR-positive patients, the 2-year survival rate was as follows: GKRS with TKIs (63.7%) and GKRS alone (44.4%) with a p-value of 0.085 and hazard ratio of 0.53 in multivariate analysis (Table 2). As shown in Fig. 1D, among EGFR wild-type patients, the 2-year survival rate was as follows: GKRS with TKIs (30.9%) and GKRS alone (55.7%)) with a p-value of 0.049 and hazard ratio of 1.819 in multivariate analysis (Table 3).
Intracranial tumor control after GKRS
The median image follow-up duration time was 12.3 months. Local tumor control of all tumors (n=1982) was as follows: 6 months (92.0%), 12 months (87.0%), 18 months (84.8%), 24 months (82.3%), and 36 months (80.5%) (Figure 2A). We did not observe a significant difference between cases of EGFR mutation and EGFR wild-type in terms of local tumor control (p = 0.53) (Figure 2B). We did not observe a significant difference between treatment modalities (GKRS with TKIs versus GKRS alone) in terms of local tumor control, regardless of tumor type (EGFR positive or wild-type) (Figure 2C, D).
Distal intracranial tumor control of all tumors was as follows: 6 months (58.0%), 12 months (38.6%), 18 months (28.5%), 24 months (22.2%), and 36 months (10.6%) (Figure 3A). We did not observe a significant difference between EGFR mutation and EGFR wild-type in terms of distal intracranial tumor control (p = 0.30) (Figure 3B). Among EGFR positive patients, GKRS with TKIs outperformed GKRS alone: 6 months (60.0 vs 50.8%), 12 months (39.9 vs 29.0%), and 24 months (22.1 vs 14.5%) (Figure 3C) with a p-value of <0.001 and hazard ratio of 0.507 in multivariate analysis (Table 2). Among EGFR wild-type patients GKRS with TKIs did not attain the effectiveness of GKRS alone, as follows: 6 months (46.0 vs 64.6%), 12 months (36.4 vs 37.4%), and 24 months (19.2 vs 33.3%) (Figure 3D) with a p-value of 0.011 and hazard ratio of 1.402 in multivariate analysis (Table 3).
Other Prognostic factors associated with GKRS
EGFR positive patients benefited from WBRT and chemotherapy in terms of local tumor control; this approach was negatively associated with primary tumor control. TKI treatment proved effective in distal intracranial control; however, prior craniotomy was identified as a negative prognostic factor (Table 2). Among EGFR wild-type patients, prior craniotomy was a positive prognostic factor in terms of OS, whereas TKI use and extracranial metastasis were negative prognostic factors. Undergoing prior craniotomy, WBRT and primary tumor control disclose negative effect on local tumor control. TKIs is the only positive factor under our criteria (Table 3). In the current study, statistically significant treatment effects were defined as a p-value <0.05 concurrently with a hazard ratio (HR) of >1.4 or <0.7 in multivariate analysis.