The effectiveness and cost-effectiveness of intraoperative imaging in high-grade glioma resection; a comparative review of intraoperative ALA, fluorescein, ultrasound and MRI

• ALA-FIGS in HGG has 82.6% sensitivity, 88.8% specificity, 97.4% PPV, 69.1% GTR and cost-effective cost/QALY.
• FLCN-FIGS in HGG has 86.6% sensitivity, 95.1% specificity, 84.4% GTR and cost-effective cost/QALY.
• IoUS in HGG has 95-88% sensitivity, 95-42% specificity, 98-62% PPV, 73.4% GTR and cost-effective cost/QALY.
• IoMRI in HGG has 55% sensitivity, 96% specificity, 70% GTR and cost-effective cost/QALY.
• There were no statistically significant differences between the different modalities in terms of GTR, sensitivity and specificity in HGG.

BackgroundSurgical resection of high-grade gliomas (HGG) is standard therapy because it imparts significant progression free (PFS) and overall survival (OS). However, HGG-tumor margins are indistinguishable from normal brain during surgery. Hence intraoperative technology such as fluorescence (ALA, fluorescein) and intraoperative ultrasound (IoUS) and MRI (IoMRI) has been deployed. This study compares the effectiveness and cost-effectiveness of these technologies.MethodsCritical literature review and meta-analyses, using MEDLINE/PubMed service. The list of references in each article was double-checked for any missing references. We included all studies that reported the use of ALA, fluorescein (FLCN), IoUS or IoMRI to guide HGG-surgery. The meta-analyses were conducted according to statistical heterogeneity between studies. If there was no heterogeneity, fixed effects model was used; otherwise, a random effects model was used. Statistical heterogeneity was explored by χ2 and inconsistency (I2) statistics. To assess cost-effectiveness, we calculated the incremental cost per quality-adjusted life-year (QALY).ResultsGross total resection (GTR) after ALA, FLCN, IoUS and IoMRI was 69.1%, 84.4%, 73.4% and 70% respectively. The differences were not statistically significant. All four techniques led to significant prolongation of PFS and tended to prolong OS. However none of these technologies led to significant prolongation of OS compared to controls. The cost/QALY was $16,218, $3181, $6049 and $32,954 for ALA, FLCN, IoUS and IoMRI respectively.ConclusionsALA, FLCN, IoUS and IoMRI significantly improve GTR and PFS of HGG. Their incremental cost was below the threshold for cost-effectiveness of HGG-therapy, denoting that each intraoperative technology was cost-effective on its own.