Survival Analysis of Patients Undergoing Intraoperative Contrast-enhanced Ultrasound in the Surgical Treatment of Malignant Glioma

Abstract

Objective

Complete resection of malignant gliomas is often challenging. Our previous study indicated that intraoperative contrast-enhanced ultrasound (ICEUS) could aid in the detection of residual tumor remnants and the total removal of brain lesions. This study aimed to investigate the survival rates of patients undergoing resection with or without the use of ICEUS and to assess the impact of ICEUS on the prognosis of patients with malignant glioma.

Methods

A total of 64 patients diagnosed with malignant glioma (WHO grade HI and IV) who underwent surgery between 2012 and 2018 were included. Among them, 29 patients received ICEUS. The effects of ICEUS on overall survival (OS) and progression-free survival (PFS) of patients were evaluated. A quantitative analysis was performed to compare ICEUS parameters between gliomas and the surrounding tissues.

Results

The ICEUS group showed better survival rates both in OS and PFS than the control group. The univariate analysis revealed that age, pathology and ICEUS were significant prognostic factors for PFS, with only age being a significant prognostic factor for OS. In multivariate analysis, age and ICEUS were significant prognostic factors for both OS and PFS. The quantitative analysis showed that the intensity and transit time of microbubbles reaching the tumors were significantly different from those of microbubbles reaching the surrounding tissue.

Conclusion

ICEUS facilitates the identification of residual tumors. Age and ICEUS are prognostic factors for malignant glioma surgery, and use of ICEUS offers a better prognosis for patients with malignant glioma.

Keywords

intraoperative contrast-enhanced ultrasound / malignant glioma / extent of resection / survival / prognosis

References

[1]	Weller M, Wick W, Aldape K, et al. Glioma. Nat Rev Dis Primers, 2015,1:15017
[2]	Wen PY, Kesari S. Malignant gliomas in adults. N Engl J Med, 2008,359(5):492–507
[3]	Louis DN, Ohgaki H, Wiestler OD, et al. The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol, 2007,114(2):97–109
[4]	Galbraith K, Snuderl M. Molecular Pathology of Gliomas. Surg Pathol Clin, 2021,14(3):379–386
[5]	Schiff D, Van den Bent M, Vogelbaum MA, et al. Recent developments and future directions in adult lower-grade gliomas: Society for Neuro-Oncology (SNO) and European Association of Neuro-Oncology (EANO) consensus. Neuro Oncol, 2019,21(7):837–853
[6]	Colman H. Adult Gliomas. Continuum (Minneap Minn), 2020,26(6):1452–1475
[7]	Unsgaard G, Gronningsaeter A, Ommedal S, et al. Brain operations guided by real-time two-dimensional ultrasound: new possibilities as a result of improved image quality. Neurosurgery, 2002,51(2):402–411; discussion 411–412
[8]	Petridis AK, Anokhin M, Vavruska J, et al. The value of intraoperative sonography in low grade glioma surgery. Clin Neurol Neurosurg, 2015,131:64–68
[9]	Le Roux PD, Berger MS, Wang K, et al. Low grade gliomas: comparison of intraoperative ultrasound characteristics with preoperative imaging studies. J Neurooncol, 1992,13(2):189–198
[10]	LeRoux PD, Winter TC, Berger MS, et al. A comparison between preoperative magnetic resonance and intraoperative ultrasound tumor volumes and margins. J Clin Ultrasound, 1994,22(1):29–36
[11]	Tao AY, Chen X, Zhang LY, et al. Application of Intraoperative Contrast-Enhanced Ultrasound in the Resection of Brain Tumors. Curr Med Sci, 2022,42(1):169–176
[12]	Prada F, Bene MD, Fornaro R, et al. Identification of residual tumor with intraoperative contrast-enhanced ultrasound during glioblastoma resection. Neurosurg Focus, 2016,40(3):E7
[13]	Wang J, Yang Y, Liu X, et al. Intraoperative contrast-enhanced ultrasound for cerebral glioma resection and the relationship between microvascular perfusion and microvessel density. Clin Neurol Neurosurg, 2019,186:105512
[14]	Prada F, Mattei L, Del Bene M, et al. Intraoperative cerebral glioma characterization with contrast enhanced ultrasound. Biomed Res Int, 2014:2014:484261
[15]	Stupp R, Mason WP, van den Bent MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med, 2005,352(10):987–996
[16]	Comba A, Faisal SM, Varela ML, et al. Uncovering Spatiotemporal Heterogeneity of High-Grade Gliomas: From Disease Biology to Therapeutic Implications. Front Oncol, 2021,11:703764
[17]	Hong JB, Roh TH, Kang SG, et al. Survival, Prognostic Factors, and Volumetric Analysis of Extent of Resection for Anaplastic Gliomas. Cancer Res Treat, 2020,52(4):1041–1049
[18]	Louis DN, Perry A, Wesseling P, et al. The 2021 WHO Classification of Tumors of the Central Nervous System: a summary. Neuro Oncol, 2021,23(8):1231–1251
[19]	Gritsch S, Batchelor TT, Gonzalez Castro LN. Diagnostic, therapeutic, and prognostic implications of the 2021 World Health Organization classification of tumors of the central nervous system. Cancer, 2022,128(1):47–58
[20]	Li YM, Suki D, Hess K, et al. The influence of maximum safe resection of glioblastoma on survival in 1229 patients: Can we do better than gross-total resection? J Neurosurg, 2016,124(4):977–88
[21]	Harrer JU, Hornen S, Oertel MF, et al. Comparison of perfusion harmonic imaging and perfusion mr imaging for the assessment of microvascular characteristics in brain tumors. Ultraschall Med, 2008,29(1):45–52
[22]	Prada F, Perin A, Martegani A, et al. Intraoperative contrast-enhanced ultrasound for brain tumor surgery. Neurosurgery, 2014,74(5):542–552
[23]	Plate KH, Risau W. Angiogenesis in malignant gliomas. Glia, 1995,15(3):339–347
[24]	Ahir BK, Engelhard HH, Lakka SS. Tumor Development and Angiogenesis in Adult Brain Tumor: Glioblastoma. Mol Neurobiol, 2020,57(5):2461–2478
[25]	Sastry R, Bi WL, Pieper S, et al. Applications of Ultrasound in the Resection of Brain Tumors. J Neuroimaging, 2017,27(1):5–15
[26]	Shang Y, Xie X, Luo Y, et al. Safety findings after intravenous administration of sulfur hexafluoride microbubbles to 463,434 examinations at 24 centers. Eur Radiol, 2023,33(2):988–995
[27]	Schaible J, Stroszczynski C, Beyer LP, et al. Quantitative perfusion analysis of hepatocellular carcinoma using dynamic contrast enhanced ultrasound (CEUS) to determine tumor microvascularization. Clin Hemorheol Microcirc, 2019,73(1):95–104
[28]	Cheng LG, He W, Zhang HX, et al. Intraoperative Contrast Enhanced Ultrasound Evaluates the Grade of Glioma. Biomed Res Int, 2016:2016:643862
[29]	Lassau N, Chami L, Chebil M, et al. Dynamic contrast-enhanced ultrasonography (DCE-US) and anti-angiogenic treatments. Discov Med, 2011,11(56):18–24
[30]	Hervey-Jumper SL, Berger MS. Maximizing safe resection of low- and high-grade glioma. J Neurooncol, 2016,130(2):269–282