Contemporary assessment of extent of resection in molecularly defined categories of diffuse low-grade glioma: a volumetric analysis

Abstract

Objective: While the effect of increased extent of resection (EOR) on survival in diffuse infiltrating low-grade glioma (LGG) patients is well established, there is still uncertainty about the influence of the new WHO molecular subtypes. The authors designed a retrospective analysis to assess the interplay between EOR and molecular classes.

Methods: The authors retrospectively reviewed the records of 326 patients treated surgically for hemispheric WHO grade II LGG at Brigham and Women's Hospital and Massachusetts General Hospital (2000-2017). EOR was calculated volumetrically and Cox proportional hazards models were built to assess for predictive factors of overall survival (OS), progression-free survival (PFS), and malignant progression-free survival (MPFS).

Results: There were 43 deaths (13.2%; median follow-up 5.4 years) among 326 LGG patients. Median preoperative tumor volume was 31.2 cm3 (IQR 12.9-66.0), and median postoperative residual tumor volume was 5.8 cm3 (IQR 1.1-20.5). On multivariable Cox regression, increasing postoperative volume was associated with worse OS (HR 1.02 per cm3; 95% CI 1.00-1.03; p = 0.016), PFS (HR 1.01 per cm3; 95% CI 1.00-1.02; p = 0.001), and MPFS (HR 1.01 per cm3; 95% CI 1.00-1.02; p = 0.035). This result was more pronounced in the worse prognosis subtypes of IDH-mutant and IDH-wildtype astrocytoma, for which differences in survival manifested in cases with residual tumor volume of only 1 cm3. In oligodendroglioma patients, postoperative residuals impacted survival when exceeding 8 cm3. Other significant predictors of OS were age at diagnosis, IDH-mutant and IDH-wildtype astrocytoma classes, adjuvant radiotherapy, and increasing preoperative volume.

Conclusions: The results corroborate the role of EOR in survival and malignant transformation across all molecular subtypes of diffuse LGG. IDH-mutant and IDH-wildtype astrocytomas are affected even by minimal postoperative residuals and patients could potentially benefit from a more aggressive surgical approach.

Keywords: astrocytoma; extent of resection; low-grade glioma; oligodendroglioma; oncology; volumetric analysis.

FIG. 1.

Kaplan-Meier curves of OS stratified by molecular group. IDHmut = IDH mutant; IDHwt = IDH wildtype.

FIG. 2.

Kaplan-Meier curves of OS stratified by categories of increasing postoperative residuals in all patients (A), oligodendroglioma patients (B), IDH-mutant astrocytoma patients (C), and IDH-wildtype astrocytoma patients (D). p values are log-rank across the 4 categories.

FIG. 3.

Scatterplot and estimated regression line (translucent bands represent 95% CIs) demonstrating the significant association of preoperative tumor volume with achieved EOR across molecular subtypes.