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

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  • 1 Computational Neuroscience Outcomes Center, Department of Neurosurgery, Brigham and Women’s Hospital;
  • 2 Harvard Medical School;
  • 3 Department of Radiology, Brigham and Women’s Hospital;
  • 4 Department of Medical Oncology, Dana-Farber Cancer Institute;
  • 5 Department of Pathology, Brigham and Women’s Hospital; and
  • 6 Center for Neuro-Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts
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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.

ABBREVIATIONS CPH = Cox proportional hazards; EOR = extent of resection; GTR = gross-total resection; iMRI = intraoperative MRI; LGG = low-grade glioma; MPFS = malignant progression–free survival; NTR = near-total resection; OS = overall survival; PFS = progression-free survival; STR = subtotal resection.

Supplementary Materials

    • pdf Supplementary Tables and Figures (PDF 2.60 MB)

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Contributor Notes

Correspondence Vasileios K. Kavouridis: Brigham and Women’s Hospital, Harvard Medical School, Boston, MA. vkavouridis@bwh.harvard.edu.

ACCOMPANYING EDITORIAL DOI: 10.3171/2019.7.JNS191747.

INCLUDE WHEN CITING Published online October 25, 2019; DOI: 10.3171/2019.6.JNS19972.

Disclosures Dr. Reardon reports receiving clinical or research support for the study described (includes equipment or material) from Acerta Pharmaceuticals, Agenus, Celldex, EMD Serono, Incyte, Inovio, Midatech, Omniox, and Tragara.

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