Functional mapping-guided resection of low-grade gliomas in eloquent areas of the brain: improvement of long-term survival. Clinical article

Abstract

Object: Low-grade gliomas (LGGs) frequently infiltrate highly functional or "eloquent" brain areas. Given the lack of long-term survival data, the prognostic significance of eloquent brain tumor location and the role of functional mapping during resective surgery in presumed eloquent brain regions are unknown.

Methods: We performed a retrospective analysis of 281 cases involving adults who underwent resection of a supratentorial LGG at a brain tumor referral center. Preoperative MR images were evaluated blindly for involvement of eloquent brain areas, including the sensorimotor and language cortices, and specific subcortical structures. For high-risk tumors located in presumed eloquent brain areas, long-term survival estimates were evaluated for patients who underwent intraoperative functional mapping with electrocortical stimulation and for those who did not.

Results: One hundred and seventy-four patients (62%) had high-risk LGGs that were located in presumed eloquent areas. Adjusting for other known prognostic factors, patients with tumors in areas presumed to be eloquent had worse overall and progression-free survival (OS, hazard ratio [HR] 6.1, 95% CI 2.6-14.1; PFS, HR 1.9, 95% CI 1.2-2.9; Cox proportional hazards). Confirmation of tumor overlapping functional areas during intraoperative mapping was strongly associated with shorter survival (OS, HR 9.6, 95% CI 3.6-25.9). In contrast, when mapping revealed that tumor spared true eloquent areas, patients had significantly longer survival, nearly comparable to patients with tumors that clearly involved only noneloquent areas, as demonstrated by preoperative imaging (OS, HR 2.9, 95% CI 1.0-8.5).

Conclusions: Presumed eloquent location of LGGs is an important but modifiable risk factor predicting disease progression and death. Delineation of true functional and nonfunctional areas by intraoperative mapping in high-risk patients to maximize tumor resection can dramatically improve long-term survival.

Fig. 1

Algorithm for analysis and grouping by treatment in this study. Preoperative MR images from 281 patients with LGGs were blindly reviewed for tumor location that occupied presumed eloquent locations, based upon anatomical criteria. Those patients with tumors in presumed eloquent locations were considered to be “high-risk” and were further stratified by whether they underwent intraoperative functional mapping. Cases in which tumors were confirmed to be in an eloquent location were designated as “true eloquent” compared with those that were determined by mapping to be adjacent but not directly overlapping eloquent brain (“false eloquent”).

Fig. 2

Representative schematic illustrations of eloquent tumor locations in left lateral view for cortical sites (A) and axial transection for deeper subcortical sites (B). Red signifies language areas; blue, sensorimotor cortex; green, deep subcortical structures, including the thalamus, basal ganglia, and internal capsule. The 3 circle sizes designate tumor diameter in centimeters.

Fig. 3

A and B: Kaplan-Meier survival estimates of OS (A) and PFS (B) stratified by “presumed eloquence” on MR images. C and D: Kaplan-Meier survival estimates of OS (C) and PFS (D) stratified by specific eloquent regions. (Probability values based on log-rank test.)

Fig. 4

Kaplan-Meier survival estimates of OS (A) and KPS (B) stratified by subgroups. “False Eloquent Mapping” refers to cases in which the brain region was preoperatively presumed to be eloquent based on anatomical imaging, but was actually not eloquent based on intraoperative functional mapping. “True Eloquent Mapping” refers to those cases in which intraoperative functional mapping confirmed the anatomical imaging determination of eloquence. (Probability values based on log-rank test.)

Fig. 5

Surgical extent of resection stratified by mapping subgroups. The black line corresponds to the median value for each subgroup data distribution (circles).