IDH–wild-type glioblastoma cell density and infiltration distribution influence on supramarginal resection and its impact on overall survival: a mathematical model

Abstract

OBJECTIVE Recent studies have proposed resection of the T2 FLAIR hyperintensity beyond the T1 contrast enhancement (supramarginal resection [SMR]) for IDH–wild-type glioblastoma (GBM) to further improve patients’ overall survival (OS). GBMs have significant variability in tumor cell density, distribution, and infiltration. Advanced mathematical models based on patient-specific radiographic features have provided new insights into GBM growth kinetics on two important parameters of tumor aggressiveness: proliferation rate (ρ) and diffusion rate (D). The aim of this study was to investigate OS of patients with IDH–wild-type GBM who underwent SMR based on a mathematical model of cell distribution and infiltration profile (tumor invasiveness profile). METHODS Volumetric measurements were obtained from the selected regions of interest from pre- and postoperative MRI studies of included patients. The tumor invasiveness profile (proliferation/diffusion [ρ/D] ratio) was calculated using the following formula: ρ/D ratio = (4π/3)2/3 × (6.106/[VT21/1 − VT11/1])2, where VT2 and VT1 are the preoperative FLAIR and contrast-enhancing volumes, respectively. Patients were split into subgroups based on their tumor invasiveness profiles. In this analysis, tumors were classified as nodular, moderately diffuse, or highly diffuse. RESULTS A total of 101 patients were included. Tumors were classified as nodular (n = 34), moderately diffuse (n = 34), and highly diffuse (n = 33). On multivariate analysis, increasing SMR had a significant positive correlation with OS for moderately and highly diffuse tumors (HR 0.99, 95% CI 0.98–0.99; p = 0.02; and HR 0.98, 95% CI 0.96–0.99; p = 0.04, respectively). On threshold analysis, OS benefit was seen with SMR from 10% to 29%, 10% to 59%, and 30% to 90%, for nodular, moderately diffuse, and highly diffuse, respectively. CONCLUSIONS The impact of SMR on OS for patients with IDH–wild-type GBM is influenced by the degree of tumor invasiveness. The authors’ results show that increasing SMR is associated with increased OS in patients with moderate and highly diffuse IDH–wild-type GBMs. When grouping SMR into 10% intervals, this benefit was seen for all tumor subgroups, although for nodular tumors, the maximum beneficial SMR percentage was considerably lower than in moderate and highly diffuse tumors.

A Systematic Review and Meta-Analysis of Supramarginal Resection versus Gross Total Resection in Glioblastoma: Can We Enhance Progression-Free Survival Time and Preserve Postoperative Safety?

“…Nevertheless, the rates of other new postoperative neurological complications (e.g., speech impairment, visual impairment, seizure, cognitive/memory status, and sensory deficits) were not significantly different among the completely resected tumors with <53.21% or ≥53.21% resection of the surrounding FLAIR abnormality. In contrast, the studies by Tripathi et al [ 10 ] and Vivas-Buitrago et al [ 43 ] identified lower optimum thresholds ranging from 10 to 20% and at 20% of an additional resection of FLAIR abnormalities surrounding the contrast-enhancing portion regarding the improvement of OS. Furthermore, the study by Vivas-Buitrago et al [ 43 ] also observed that a significant benefit with regard to PFS can be found in patients who underwent a resection of 20 to 40% of the surrounding FLAIR abnormality beyond the conventional GTR of the contrast-enhancing portion, but no significant influence has been shown in patients who underwent an additional FLAIR resection of 50% or greater.…”

“…Although it is known that glioma cells can be found throughout the brain, up to 80% of patients develop initial tumor recurrence in close proximity to the resection site ( (accessed on 1 February 2023)) [ 5 , 6 , 7 ]. Reasons for this might be manifold, e.g., the growth-promoting influence of peri-tumoral microenvironments, local glioma regrowth with help of functional tumor cell networks, or simply higher tumor cell density around the resection cavity [ 8 , 9 , 10 ].…”

Update for astrocytomas: medical and surgical management considerations

“…A number of studies have suggested ideal average ranges of FLAIR resection ranging from 20-53% [160][161][162][163]. A more recent study by Tripathi et al [164] suggests that the ideal SMR volume for GBs depends on the physiology of the tumor, with a range of 10-29% for nodular, 10-59% for moderately diffuse, and 30-90% for highly diffuse. One retrospective analysis of 102 patients with GBs showed a statistically significant 6.06-month median overall survival improvement in SMR when compared with GTR [165].…”

Bilateral Laser Interstitial Thermal Therapy for Butterfly Gliomas Compared With Needle Biopsy: A Preliminary Survival Study

“…The region of interest tool was used to delineate the borders of the tumor throughout all the MRI slices, and an automatic volume calculation was then performed by the software, as previously described. [12][13][14] For patients undergoing LITT, the preoperative, postoperative, and ablation volumes were obtained. For patients undergoing biopsy, only the preoperative volume was obtained.…”