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

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  • 1 Department of Neurosurgery, Mayo Clinic, Jacksonville, Florida;
  • | 2 Department of Neurosurgery, Mayo Clinic, Rochester, Minnesota;
  • | 3 Department of Neurosurgery, Mayo Clinic, Phoenix;
  • | 4 Mathematical Neuro-Oncology Lab, Precision Neurotherapeutics Innovation Program, Mayo Clinic, Phoenix;
  • | 5 Department of Neurology, Division of Neuro-Oncology, Mayo Clinic, Phoenix, Arizona;
  • | 6 Department of Neurology, Division of Neuro-Oncology, Mayo Clinic, Rochester, Minnesota;
  • | 7 Department of Neurology, Division of Neuro-Oncology, Mayo Clinic, Jacksonville;
  • | 8 Department of Radiology, Mayo Clinic, Jacksonville;
  • | 9 Department of Psychology, Mayo Clinic, Jacksonville, Florida;
  • | 10 Feinberg School of Medicine, Northwestern University, Chicago, Illinois; and
  • | 11 Department of Health Sciences, School of Medicine, Universidad de Santander UDES, Bucaramanga, Colombia
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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/[VT2 1/1 − VT1 1/1])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.

ABBREVIATIONS

D = diffusion rate; EOR = extent of resection; GBM = glioblastoma; GTR = gross-total resection; IDH = isocitrate dehydrogenase; KPS = Karnofsky Performance Status; MGMT = O6-methylguanine-DNA methyltransferase; OS = overall survival; PFS = progression-free survival; SMR = supramarginal resection; ρ = proliferation rate.

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