BACKGROUND:In most cases, routine neuropathological analysis can clearly distinguish between methylated and unmethylated MGMT promoters in glioblastoma (GBM). However, some GBMs display weak MGMT promoter methylation. This study aimed to evaluate its impact on disease progression and survival compared with fully methylated and unmethylated cases. METHODS:A quantitative analysis of MGMT promoter methylation was performed on 140 of 190 samples from a cohort of adult patients with newly diagnosed GBM. The MGMT promoter was stratified into three subgroups based on methylation status: unmethylated, weakly methylated (9-28%), and methylated (29-100%). These cut-off values were selected based on previously published data demonstrating significant differences in progression-free survival (PFS) and overall survival (OS) among patients with these categories. Clinical characteristics, treatment regimens, and survival outcomes were analyzed and compared. Cox proportional hazards regression was used to evaluate the impact of MGMT methylation status on progression-free interval (PFI) and overall survival (OS). RESULTS:The MGMT promoter was unmethylated in 57 (40.7%) samples, methylated in 66 (47.1%) samples, and weakly methylated in 17 (12.1%) samples. Compared to patients with methylated and unmethylated MGMT promoters, the PFI of patients with weak MGMT methylation was comparable (P=0.53) and the OS was slightly longer (P=0.08). After stratification following chemoradiotherapy consisting of TMZ, patients with weakly methylated MGMT have a longer PFI. The Cox proportional hazards regression model revealed that a weakly methylated MGMT promoter was a significant risk factor for longer OS (P=0.02), while older age remained an unfavorable prognostic factor for survival (P<0.001). CONCLUSIONS:Weak MGMT promoter methylation may offer clinical benefits comparable to full methylation, including longer PFI and improved OS compared to unmethylated cases. This positive effect on PFI appears more pronounced in patients receiving concurrent chemoradiotherapy with TMZ. Advanced age continues to be associated with a less favorable prognosis.
BACKGROUND:Despite wide variation in the outcomes and costs of lumbar fusion, few studies have integrated these domains together within a single metric to assess "value" (outcomes achieved per dollar spent). In this review, we sought to 1) characterize existing metrics of cost-effectiveness for lumbar fusion, 2) evaluate all applications of time-driven activity-based costing (TDABC) in spine surgery, and 3) outline the conceptual foundation for a standardized Operative Value Index (OVI). METHODS:Two PRISMA-concordant systematic reviews were performed on PubMed and Scopus databases. The first review examined all studies which reported a cost-effectiveness metric for lumbar fusion. The second review examined all applications of TDBAC in spine surgery. RESULTS:Among 366 screened studies, 40 (21 for cost-effectiveness in lumbar fusion, 19 for TDABC in spine surgery) fulfilled inclusion criteria. The incremental cost-effectiveness ratio (ICER) was the most common metric, followed by OVI. Costs were frequently defined as reimbursement or charges; few studies assessed actual costs or TDABC. TDABC studies consistently demonstrated that costs were driven primarily by surgeon-level and procedure-specific factors, not patient characteristics. OVI studies uniformly used TDABC costs combined with disease-specific outcomes, but were limited to short-term follow-up and primarily intraoperative costs. CONCLUSIONS:Current value assessments in lumbar fusion are limited by heterogeneous outcomes and imprecise costing. A standardized framework integrating pathology-specific outcomes with episode-level costing (not charges or reimbursement) may enable more generalizable and accurate comparisons of operative value.
