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

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 cm(3) (IQR 12.9-66.0), and median postoperative residual tumor volume was 5.8 cm(3) (IQR 1.1-20.5). On multivariable Cox regression, increasing postoperative volume was associated with worse OS (HR 1.02 per cm(3); 95% CI 1.00-1.03; p = 0.016), PFS (HR 1.01 per cm(3); 95% CI 1.00-1.02; p = 0.001), and MPFS (HR 1.01 per cm(3); 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 cm(3). In oligodendroglioma patients, postoperative residuals impacted survival when exceeding 8 cm(3). 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.