Incidental diffuse low-grade gliomas: A systematic review and meta-analysis of treatment results with correction of lead-time and length-time biases

Abstract Background Better overall survival (OS) reported in patients with incidental diffuse low-grade glioma (iLGG) in comparison to symptomatic LGG (sLGG) may be overestimated by lead-time and length-time. Method We performed a systematic review and meta-analysis of studies on adult hemispheric iLGGs according to the PRISMA statement to adjust for biases in their outcomes. Survival data were extracted from Kaplan-Meier curves. Lead-time was estimated by two methods: pooled data of time to become symptomatic (LTs) and time calculated from tumor growth model (LTg). Results We selected articles from PubMed, Ovid Medline, and Scopus since 2000. Five compared OS between patients with iLGG (n = 287) and sLGG (n = 3117). The pooled hazard ratio (pHR) for OS of iLGG to sLGG was 0.40 (95% confidence interval (CI) [0.27-0.61]). The estimated mean LTs and LTg were 3.76 years (n = 50) and 4.16 - 6.12 years, respectively. The corrected pHRs were 0.64 (95%CI [0.51-0.81] by LTs and 0.70 (95%CI [0.56-0.88]) by LTg. In patients with total removal, the advantage of OS in iLGG was lost after correction of lead-time. Patients with iLGG were more likely to be female (pooled odds ratio (pOR) 1.60 (95%CI [1.25-2.04]) and have oligodendrogliomas (pOR 1.59 (95%CI [1.05-2.39]). Correction of the length-time bias, which increased the pHR by 0.01 to 0.03, preserved the statistically significant difference in OS. Conclusions The reported outcome in iLGG was biased by lead-time and length-time. Although iLGG had a longer OS after correction of biases, the difference was less than previously reported.