Extensive Resection Boosts Survival in Low-Grade Brain Tumor

A recent reclassification of brain tumors based on molecular subtypes has led to questions over whether extensive surgery is the best approach for some tumor types or whether chemoradiotherapy may be considered instead.

A new analysis confirms that for patients with low-grade glioma (LGG), extensive tumor resection is associated with improved survival, regardless of the tumor subtype.

The study of over 750 patients with grade 2 astrocytoma or oligodendroglioma showed that with extent of surgical tumor resection (EOR) of ≥75%, there was significant overall survival benefit and that an EOR of ≥80% was associated with improved progression-free survival (PFS).

“Our findings put an end to the controversy that maximal resection may not be required for some low-grade gliomas,” said study first author Shawn L. Hervey-Jumper, MD, Department of Neurological Surgery, University of California, San Francisco, in a statement.

“Even for oligodendrogliomas, there is no question that maximal resection is critical for enhancing survival,” he added.

The research was published online in Journal of Clinical Oncology on January 4.

“Studies that did not follow patients for as long as we did have raised questions about the need for maximal surgery, especially in oligodendroglioma,” commented co–senior author Annette M. Molinaro, PhD, Department of Neurological Surgery, University of California, San Francisco.

“But we found that resecting as much as possible soon after diagnosis offered a distinct survival advantage when we looked at the disease trajectory 10 years later.”

However, such surgery should not be at the “expense of deficits,” observed co–senior author Mitchel S. Berger, MD, Department of Neurological Surgery, University of California, San Francisco.

This is particularly the case when considering whether to perform gross total resection (GTR) or GTR+, in which a margin of apparently healthy tissue is resected with the tumor, he underlined.

Recent Controversy

The authors note that despite their relatively slow growth, LGGs are “locally invasive and prone to malignant transformation.”

Until recently, more extensive tumor resection was the standard of care because it was associated with longer survival, they add.

However, in 2016, the World Health Organization reclassified diffuse gliomas on the basis of their tumor histology and molecular characteristics.

This led to suggestions that the benefits of extensive resection apply only to certain molecular subgroups of tumors.

In particular, it is argued that “complete surgical resection for patients with oligodendroglioma may not offer a survival advantage,” the authors write, and that chemoradiotherapy may yield a better response.

This has, they add, created “controversy and confusion among both providers and patients.”

They set out to clarify the issue by conducting a retrospective analysis of 392 patients with IDH-mutant grade 2 glioma. The patients were followed for a median of 11.7 years.

The investigars compared the outcomes of these patients with those in two external cohorts totaling 365 patients.

A propensity score analysis of the combined cohort of 757 patients was carried out to mimic a randomized clinical trial of varying EOR levels.

The median overall survival in the development cohort was 19.9 years, the median PFS was 8.65 years, and the median malignant transformation-free survival (MTFS) was 18.6 years. Among patients with astrocytoma, the median overall survival was 13.1 years, the median PFS was 5.7 years, and the median MTFS was 18.6 years.

The researchers subsequently identified three survival risk groups, using the following four key characteristics:

  • Postoperative tumor volume >4.6 mL

  • Preoperative tumor volume >43.1 mL

  • LGG disease subtype

  • Whether or not a patient received chemotherapy

The median overall survival, at a median of 9.0 years, was shortest among patients with astrocytoma of larger postoperative tumor volume and among those with smaller postoperative tumor volume but larger preoperative tumor volume.

At a median of 19.9 years, intermediate overall survival occurred among patients with astrocytoma of smaller preoperative and postoperative tumor volume who received chemotherapy and among patients with oligodendroglioma of either larger preoperative tumor volume and smaller residual tumor volume or larger postoperative residual volume.

The longest overall survival was observed among patients with astrocytoma of smaller preoperative and postoperative tumor volume who did not receive chemotherapy and among patients with oligodendroglioma of smaller preoperative and postoperative tumor volume. The median was not reached.

Overall, the team calculated that, across the development and validation cohorts, an EOR of ≥75% was associated with a significant improvement in survival outcomes, an EOR of ≥80% was associated with improved PFS, and an EOR of ≥70% was associated with improved MTFS.

The study was supported by institutional funding from National Institutes of Health, the loglio Collective, the National Brain Tumor Foundation, the Stanley D. Lewis and Virginia S. Lewis Endowed Chair in Brain Tumor Research, the Robert Magnin Newman Endowed Chair in Neuro-oncology, and by donations from families and friends of John Berardi, Helen Glaser, Elvera Olsen, Raymond E. Cooper, Resonance Philanthropies, and William Martinusen. Hervey-Jumper has relationships with Gilmartin Capital. Molinaro and Berger have disclosed no relevant financial relationships. Other authors have disclosed numerous financial relationships.

J Clin Oncol. Published online January 4, 2023. Full text

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