Rapid early progression (REP) of glioblastoma is an independent negative prognostic factor: Results from a systematic review and meta-analysis

BACKGROUND: In patients with newly diagnosed glioblastoma, rapid early progression (REP) refers to tumor regrowth between surgery and postoperative chemoradiotherapy. This systematic review and meta-analysis appraised previously published data on REP to better characterize and understand it.

METHODS: Systematic searches of MEDLINE, EMBASE and the Cochrane database from inception to October 21, 2021. Studies describing the incidence of REP-tumor growth between the postoperative MRI scan and pre-radiotherapy MRI scan in newly diagnosed glioblastoma were included. The primary outcome was REP incidence.

RESULTS: From 1590 search results, 9 studies were included with 716 patients. The median age was 56.9 years (IQR 54.0-58.8 y). There was a male predominance with a median male-to-female ratio of 1.4 (IQR 1.1-1.5). The median number of days between MRI scans was 34 days (IQR 18-45 days). The mean incidence rate of REP was 45.9% (range 19.3%-72.0%) and significantly lower in studies employing functional imaging to define REP ( P  < .001). REP/non-REP groups were comparable with respect to age ( P  = .99), gender ( P  = .33) and time between scans ( P  = .81). REP was associated with shortened overall survival (HR 1.78, 95% CI 1.30-2.43, P  < .001), shortened progression-free survival (HR 1.78, 95% CI 1.30-2.43, P  < .001), subtotal resection (OR 6.96, 95% CI 4.51-10.73, P  < .001) and IDH wild-type versus mutant tumors (OR 0.20, 95% CI 0.02-0.38, P  = .03). MGMT promoter methylation was not associated with REP (OR 1.29, 95% CI 0.72-2.28, P  = .39).

CONCLUSIONS: REP occurs in almost half of patients with newly diagnosed glioblastoma and has a strongly negative prognostic effect. Future studies should investigate its biology and effective treatment strategies.