A retrospective propensity-matched study comparing whole-brain radiotherapy with simultaneous integrated boost to whole-brain radiotherapy alone for brain metastases

Abstract

Background: The effectiveness of whole brain radiation therapy with simultaneous integrated boost (WBRT-SIB) in comparison to whole brain radiation therapy alone (WBRT-alone) is yet unknown, despite the fact that its use in clinic is growing. To investigate the variations in intracranial control and overall survival (OS) between the two approaches, we conducted a matching comparison for patients with brain metastases (BM).

Method: From January 1, 2015, to December 31, 2019, a total of 245 BM patients were eligible for inclusion, including 154 patients who received WBRT-alone (30 Gy/10 fractions) and 91 patients who received WBRT-SIB (40-50 Gy/10 fractions). 1:1 propensity score matching was used to select the patients with balanced baseline characteristics. The intracranial control and OS condition were analyzed using Kaplan-Meier method, Log-rank test, and Cox proportional hazard regression model.

Results: 138 patients were matched into the WBRT-SIB group and the WBRT-alone group. Of these, 113 (81.9%) patients had BM originating from the lungs, and 124 (89.9%) patients had more than 3 intracranial lesions. After the initiation of radiotherapy, the WBRT-SIB group and the WBRT-alone group had respective 2-year intracranial progression-free survival (iPFS), local progression-free survival (iLPFS), and distant progression-free survival (iDPFS) of 46.2% and 24.5% (p = 0.017), 49.4% and 29.8% (p = 0.033), and 68.6% and 54.4% (p = 0.040). There was no significant difference in OS (22.2 vs. 19.0 months, p = 0.768). However, in the exploratory subgroup analysis of infratentorial with/without supratentorial metastases (n = 96), the WBRT-SIB group showed a significantly better OS than the WBRT-alone group (24.6 vs.17.2 months, p = 0.040). Furthermore, the Cox proportional hazard model of this subgroup revealed that WBRT-SIB (p = 0.039) and systemic therapy after radiotherapy (p = 0.002) were independent prognostic factors for OS. There was no difference in the incidence of grade 3-4 acute brain radiation reactions between the two groups (24.6% vs. 17.4%, p = 0.290).

Conclusion: WBRT-SIB is a promising strategy for patients with BM. Compared to WBRT alone, WBRT-SIB can significantly prolong the intracranial PFS (including local and distant PFS). Additionally, while WBRT-SIB did not improve OS in the entire cohort, the OS benefit for patients with BM accompanied by infratentorial involvement warrants further exploration.

Keywords: Brain metastases; Prognosis; Simultaneous integrated boost; Whole brain radiation therapy.

Fig. 1

Flow diagram of the study design. WBRT-SIB indicates whole brain radiation therapy with simultaneous integrated boost; WBRT-alone indicates whole-brain radiation therapy

Fig. 2

(A/B) Intracranial local progression-free survival (iLPFS) and intracranial distant progression-free survival (iDPFS) in WBRT-SIB group were significantly better than WBRT-alone group (p = 0.033, p = 0.040). (C) Intracranial progression-free survival (iPFS) was significantly improved with WBRT-SIB compared with WBRT-alone (12.8 vs. 20.3 months, p = 0.017) (D) There was not significant difference in overall survival (OS) between WBRT-alone group and WBRT-SIB group (p = 0.768), and the median OS were 22.2 months and 19.0 months. (E/F) In the subgroup of infratentorial with or without supratentorial metastasis, iPFS and OS in WBRT-SIB group were significantly better than WBRT-alone group (p = 0.005, p = 0.041)