Objective: Near-infrared fluorescence with 5-aminoleulinic acid (5-ALA) is an important tool to guide resection of glioblastoma (GBM). However, in the ventricular wall and ependyma, there may be visible fluorescence in response to 5-ALA even in the absence of tumor cells. This may impact the surgical decision to continue resection into the ventricles when the GBM is located in close proximity to the subventricular zone (SVZ). The aim of this study was to determine the surgical, radiological, and oncological implications of fluorescence-guided resection (FGR) of SVZ GBM.
Methods: The electronic medical records of adult patients with newly diagnosed SVZ GBM under treatment at a tertiary medical center between January 2011 and December 2021 were retrospectively reviewed. Clinical, surgical, radiological, and outcome parameters were compared between patients resected under fluorescence guidance (FGR group) and the white light (WL)-only group, with overall and within subgroups defined by the following known prognostic factors: age (≥ 55 vs < 55 years), use of chemoradiation (yes vs no), O6-methylguanine-DNA-methyltransferase (MGMT) methylation status (methylated vs unmethylated), and performance status score (≥ 80 vs ≤ 70).
Results: The cohort included 94 patients. Compared to the WL group (n = 46), the FGR group (n = 48) was characterized by lower postoperative tumor volume (3.97 ± 6.92 cm3 vs 7.21 ± 6.81cm3, p = 0.038), greater extent of resection (90.91% ± 12.9% vs 81.19% ± 17.69%, p = 0.005), and higher rates of gross-total resection (28.6% vs 11.6%, OR 0.296, 95% CI 0.0968-0.9057, p = 0.0329). This group also had higher rates of intraoperative ventricular entry (72.9% vs 42.2%, p = 0.003) and shunt placement (by > 2.5-fold, p = 0.199). There were no significant between-group differences in distant recurrences or leptomeningeal dissemination. Gross-total resection showed a trend-level association with increased 1-year overall survival (HR 0.308, 95%CI 0.073-1.3, p = 0.089). When compared to the entire cohort, FGR was significantly associated with increased overall survival for the subgroups of patients that were < 55 years of age (HR 0.489, p = 0.026), treated with the Stupp protocol (HR 0.562, p = 0.0086), and had a Karnofsky Performance Scale score > 70 (HR 0.428, p = 0.00049), and this association reached near significance for patients with MGMT-methylated status (HR 0.512, p = 0.074). Such significant differences were not demonstrated for any of the WL subgroups.
Conclusions: FGR using 5-ALA had a significant favorable impact on extent of resection and residual tumor in patients with SVZ GBM. These positive effects associated with FGR appeared to outweigh its negative effects of increased rates of ventricular entry and shunt surgery, which had no meaningful impact on most surgical, radiological, and oncological outcomes, including survival. In patients with favorable prognostic parameters, FGR and gross-total resection were associated with clinically meaningful improved overall survival.
Keywords: 5-aminoleulinic acid; glioblastoma; oncology; shunt; subventricular zone; tumor.