Surgery Followed by Stupp Protocol with versus Without Gliadel® Wafer in Patients with Primary Glioblastoma Multiforme: A Systematic Review and Meta-analysis

Introduction: Literature has been sparse and disputed in addition of implanted Carmustin Wafer (Gliadel®) to surgery plus Stupp protocol in patients with primary glioblastoma multiforme (GBM). This systematic review and meta-analysis sought to shed light on this topic

Methods: MEDLINE, PubMed, and Embase were searched from 2004 to 10/1/2024. The primary outcomes were overall survival (month) and progression-free survival (month). Secondary outcomes were cytopenia (i.e., leukopenia, anemia, or thrombocytopenia), postoperative infection, postoperative hemorrhage, postoperative seizure, and postoperative venous thromboembolism (VTE). PROSPERO registration # CRD42024510205.

Results: Four out of 880 studies met the eligibility criteria. These studies resulted in 943 patients with primary GBM, of which 440 (46.6%) and 503 (53.4%) underwent surgery followed by Stupp protocol with and without implanted Gliadel®, respectively. Two groups were similar in age (55.5 vs. 54.6 years, p=0.458), male sex (63.1% vs. 70.0%, p=0.597), and gross total resection (55.2% vs. 58%, p=0.382). The overall survival (mean difference [MD]= 4.04 [1.72, 6.36], p=0.006) and progression-free survival (MD=1.99 [0.95, 3.04], p=0.0002) were greater in those who underwent Gliadel® implantation. Although the odds ratio (OR) of cytopenia (OR=3.36 [1.28, 8.79], p=0.01) was higher with combination therapy, the ORs of infection (OR=0.87 [0.43, 1.77], p=0.71) and resection site hemorrhage (OR=0.46 [0.13, 1.64], p=0.23) were similar between the two groups. In addition, the ORs of postoperative seizure (OR=1.49 [0.72, 3.12], p=0.29) and VTE (OR=1.19 [0.49, 2.88], p=0.70) were similar.

Conclusion : The pooled existing evidence demonstrated that adding Gliadel® to Stupp protocol is efficacious and safe for primary GBM patients.