Interactive Effects of Molecular, Therapeutic, and Patient Factors on Outcome of Diffuse Low-Grade Glioma

Abstract

PURPOSE In patients with diffuse low-grade glioma (LGG), the extent of surgical tumor resection (EOR) has a controversial role, in part because a randomized clinical trial with different levels of EOR is not feasible. METHODS In a 20-year retrospective cohort of 392 patients with IDH-mutant grade 2 glioma, we analyzed the combined effects of volumetric EOR and molecular and clinical factors on overall survival (OS) and progression-free survival by recursive partitioning analysis. The OS results were validated in two external cohorts (n = 365). Propensity score analysis of the combined cohorts (n = 757) was used to mimic a randomized clinical trial with varying levels of EOR. RESULTS Recursive partitioning analysis identified three survival risk groups. Median OS was shortest in two subsets of patients with astrocytoma: those with postoperative tumor volume (TV) > 4.6 mL and those with preoperative TV > 43.1 mL and postoperative TV ≤ 4.6 mL. Intermediate OS was seen in patients with astrocytoma who had chemotherapy with preoperative TV ≤ 43.1 mL and postoperative TV ≤ 4.6 mL in addition to oligodendroglioma patients with either preoperative TV > 43.1 mL and residual TV ≤ 4.6 mL or postoperative residual volume > 4.6 mL. Longest OS was seen in astrocytoma patients with preoperative TV ≤ 43.1 mL and postoperative TV ≤ 4.6 mL who received no chemotherapy and oligodendroglioma patients with preoperative TV ≤ 43.1 mL and postoperative TV ≤ 4.6 mL. EOR ≥ 75% improved survival outcomes, as shown by propensity score analysis. CONCLUSION Across both subtypes of LGG, EOR beginning at 75% improves OS while beginning at 80% improves progression-free survival. Nonetheless, maximal resection with preservation of neurological function remains the treatment goal. Our findings have implications for surgical strategies for LGGs, particularly oligodendroglioma.

Technical Aspects of Motor and Language Mapping in Glioma Patients

“…Maximal safe resection is defined as resecting as much tumor-infiltrated tissue as possible to improve survival while minimizing the risk of postoperative neurological deficits and retaining quality of life [ 2 , 25 , 26 , 27 ]. As mentioned, SpTR has recently been associated with improved overall survival (OS) for both LGG and GBM [ 2 , 28 ]; however, the survival advantage of these more aggressive resections is lost when patients have a postoperative deficit [ 8 , 9 , 10 ]. As such, significant efforts have been made to develop pre- and intra-operative methods for maximizing EOR.…”

MGMT Methylation Status in Grades 2 and 3 Gliomas Is Important, but Is It Prognostic?

“…The extent of tumor resection is a significant factor in determining low-risk vs high-risk outcomes in grades 2 and 3 gliomas. Studies have demonstrated that PFS and OS benefit when comparing gross total resections with subtotal resections in low-grade gliomas . Worse performance status has similarly demonstrated an association with worse OS and PFS in patients with low-grade gliomas .…”

“…While Kinslow et al included age, sex, IDH variant status, 1p/19q codeletion status, chemotherapy, radiotherapy, and MGMT promoter methylation status as covariables, they failed to account for extent of resection or Karnofsky performance status, 2 well-established prognostic indicators . These data were missing from the MSK-IMPACT cohort; therefore, they were not included in the final analysis.…”

Long-Term Outcomes in Resected IDH-Mutant Subtypes of Diffuse Low-Grade Glioma

“…Hervey-Jumper et al 1 have written a timely paper about the management of low‐grade glioma (LGG) as recently redefined. The WHO publications on LGG in 2016 and 2021 2 have grouped LGG into more precise variants whose biological behavior is better known.…”

“…The patients included in the analysis by Hervey-Jumper et al 1 are different from cases included in trials about chemotherapy for astrocytoma (Table 1). In the analysis by Hervey-Jumper et al, 1 all patients had astrocytoma IDH-mutant, all were resectable, and most had an extensive resection.…”