This study was conducted to investigate the efficacy and safety of temozolomide (TMZ) with fractionated stereotactic radiotherapy (FSRT) for large brain metastases (BMs).
From 2009 to 2016, 72 patients (pts) with large BMs (diameter>3cm or volume>6cc) undergoing concurrent TMZ and FSRT (Group A, n = 38) or FSRT alone (Group B, n = 34) were compared by using the propensity score matching method at the ratio of 1:1. Finally, 27 pts of each group were matched. FSRT was given by 52-52.5Gy/3.5-4Gy/13-15f, while TMZ was given by 75mg/m2 concurrently. The disease control rate (DCR, CR+PR+SD) was assessed after 2-3 months from treatment. Toxicity was recorded according to CTCAE, v4.0. Local control (LC), intracranial progression-free survival (IPFS), progression-free survival (PFS) and overall survival (OS) were assessed with Kaplan–Meier method and log-rank test.
The median GTV of Group A and B were 19.7cc (6.02-142.81cc) and 15.7cc (6.27-62.35cc), respectively. During treatment, more lesions in Group A shrank greatly and got re-contoured (39 VS 29, p = 0.005), and the median GTV shrinkage rate was 30.5% versus (VS) 23.1%. After 2-3 months of treatment, the DCR was 97.4% (37/38) in Group A and 85.3% (29/34) in Group B (p = 0.064). The median follow-up time was 20.6 months. Before matching, the LC (p = 0.037) and PFS (p = 0.025) of Group A were significantly greater than Group B. IPFS (p = 0.059) and OS (p = 0.059) were marginally longer in Group A. After matching, the median PFS time and 1-year PFS rate of Group A were significantly greater than Group B (12.7m VS 3.3m and 55.2% VS 26.4%, respectively, p = 0.041). The rate of intracranial progression death of Group A was significantly lower (18.2% VS 45.8%, p = 0.04). Both overall survival time and IPFS were also marginally longer in Group A (MST: 23.7m VS 17.5m, p = 0.064; 1y-IPFS: 61.6% VS 40.7%, p = 0.069), while there was no significant difference in 1-y LC (89.8% VS 84.2%, p = 0.23). There was no severe toxicity in both groups (p = 0.623).
The addition of TMZ to FSRT shows advantages in accelerating the shrinkage of large BMs and might improve intracranial control and overall survival, with no increase of toxicities. Further studies with large sample sizes are warranted.
Clinical trial identification
Legal entity responsible for the study
Cancer Hospital, Chinese Academy of Medical Sciences
All authors have declared no conflicts of interest.