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Interactive Effects of Molecular, Therapeutic, and Patient Factors on Outcome of DiffuseLow-xGrade Glioma

Interactive Effects of Molecular, Therapeutic, and Patient Factors on Outcome of Diffuse

This study investigates the impact of the extent of resection (EOR) on overall survival (OS) and progression-free survival (PFS) in patients with diffuse low-grade glioma (LGG), considering the molecular and clinical heterogeneity of these tumors. Due to the impracticality of randomized clinical trials in this context, the study utilizes retrospective data and propensity score analysis to estimate the effects of varying levels of EOR.

A retrospective cohort of 392 patients with astrocytoma IDH-mutant or oligodendroglioma IDH-mutant 1p19q codeleted was analyzed. The study examined the relationships between volumetric EOR, molecular and clinical factors, and survival outcomes. Recursive partitioning analysis identified survival risk groups, which were validated in two external cohorts comprising 365 patients. Propensity score matching was used to mimic a randomized clinical trial, accounting for variables such as age, tumor subtype, chemotherapy, radiation, preoperative tumor volume, and tumor location.

Recursive partitioning analysis delineated three distinct survival risk groups based on preoperative and postoperative tumor volumes (TVs), chemotherapy use, and LGG subtype. The median OS was shortest in two subsets of astrocytoma patients: those with postoperative

TV > 4.6 mL, and those with preoperative TV > 43.1 mL and postoperative TV ≤ 4.6 mL. Intermediate OS was observed in astrocytoma patients with smaller preoperative and postoperative TVs who had undergone chemotherapy, and in oligodendroglioma patients with larger preoperative and smaller postoperative TVs. The longest OS was seen in patients with smaller preoperative and postoperative TVs who did not receive chemotherapy, and in oligodendroglioma patients with smaller preoperative and postoperative TVs. Propensity score analysis revealed that an EOR of at least 75% significantly improved OS, while an EOR of 80% or more improved PFS.

In the second analysis, they found that the relative benefit of EOR beyond the imaging-

defined tumor margin (GTR+) appears greatest for patients with astrocytoma. This important

distinction contrasts with patients with oligodendroglioma tumors, in which GTR and GTR+

demonstrated similar beneficial survival outcomes compared to patients who underwent

subtotal resection.

This study supports the hypothesis that greater EOR is associated with improved survival in patients with LGG. Specifically, the data indicate that extensive resection beyond imaging-defined tumor margins is particularly beneficial for patients with astrocytoma. The use of propensity score matching to mimic a randomized trial adds robustness to the findings, addressing the controversies surrounding the role of EOR in LGG treatment. This study reinforces the critical role of surgery in the initial management of gliomas and offers a nuanced understanding of how molecular and clinical factors interact to influence survival outcomes.


Journal: Journal of Clinical Oncology, 2023

Author: Cleiton Formentin, MD, PhD

Mini-CV: Neurological surgeon from University of Campinas, former fellow in neurosurgical

oncology (SNOLA) and skull base surgery (University of Pittsburgh).

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