Intraoperative Ultrasound Guided Glioma Surgery; a Randomised, Controlled Trial. (US-GLIOMA)

Intraoperative Ultrasound Guidance and Extent of Resection in High Grade Glioma Surgery: a Randomised, Controlled Trial.

The main goal of high grade glioma (HGG) surgery is to achieve gross total resection (GTR) without causing new neurological deficits1-8. Intraoperative navigated high resolution ultrasound (US) is a promising new tool to acquire real-time intraoperative images to localize and to resect gliomas9-12. The aim of this study was to investigate whether intraoperative guided surgery leads to a higher rate of GTR, when compared with standard non-ultrasound guided surgery.

Study Overview

• Status: Unknown
• Conditions: Glioma
• Intervention / Treatment: Procedure: ultrasound guided surgery.

Detailed Description

Study design:

The US-GLIOMA study is a randomized controlled trial with blinded primary outcome measure.

Study population:

Fifty patients with newly diagnosed contrast enhancing presumed high grade glioma on first MRI scan.

Intervention:

The study consists of two treatment arms: non-ultrasound guided glioma resection (conventional treatment) versus ultrasound guided glioma resection (intervention) .

Main study parameters/endpoints:

• Gross total resection (yes/no)
• Extent of resection (%)
• Neurological outcome (Karnofsky Performance Status)
• Quality of Life (EORTC QLQ-C30 and QLQ-BN20 quality of life questionnaire)
• Surgery associated neurological deficits (National Institutes of Health Stroke Scale)
• Adverse events (classified according to the US National Cancer Institute common toxicity criteria version 4.0)
• Survival time (days)

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Zuid-Holland
    • Rotterdam, Zuid-Holland, Netherlands
      • Erasmus MC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Individuals of 18 years or older
• Newly diagnosed, untreated, contrast enhancing presumed high-grade glioma
• KPS ≥ 60
• Preoperative intention to perform gross-total resection of the enhancing tumor
• Written informed consent conform ICH-GCP

Exclusion Criteria:

• Tumours crossing the midline basal ganglia, cerebellum, or brain stem prohibiting gross total resection
• Multifocal contrast enhancing lesions
• Pre-existing neurological deficit (e.g. aphasia, hemiparesis) due to neurological diseases (e.g. stroke)
• Inability to give consent because of dysphasia or language barrier

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ultrasound; ultrasound navigation guided surgery.	Procedure: ultrasound guided surgery.; during surgery, the neurosurgeon will acquire ultrasound guided images (fused with the standard neuronavigation system) to evaluate the progress of tumor resection.
No Intervention: Non-ultrasound; standard surgery without ultrasound guidance.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gross total resection (Yes or No)	Gross-total resection (yes vs. no): No residual contrast enhancement on post-operative MRI scans; 100% of all contrast enhancing tumor has been resected when compared to initial enhancing tumor on pre-operative MRI scans.	within 48 hours after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Extent of resection (%)	as a continous variable The extent of resection (%) is a secondary outcome measurement defined as the residual tumor volumes on post-operative MRI studies compared to the operative tumor volume.	within 48 hours after surgery
Neurological outcome (Karnofsky Performance status)	Karnofsky Performance status	within 1 week after surgery
Quality of Life (QLQ C30 questionnaires)	QLQ C30 questionnaires A brain tumor specific quality of life measurement tool	1, 3 and 6 months after surgery
Quality of Life (QLQ BN20 questionnaires)	QLQ BN20 questionnaires A brain tumor specific quality of life measurement tool	1, 3 and 6 months after surgery
Surgery associated neurological deficits (National Institutes of Health Stroke Scale)	National Institutes of Health Stroke Scale 0 No stroke symptoms 1-4 Minor stroke 5-15 Moderate stroke 16-20 Moderate to severe stroke 21-42 Severe stroke NIHSS is a tool used by healthcare providers to objectively quantify the impairment caused typically by a stroke, however it is also used for tumor studies to assess functioning on the level of speech, motor and sensory functions.	1 month after surgery
Survival (time in days)	time measured from surgery until death in days. This study has a follow up of 6 months. However, when patients are alive at months after surgery, we will contact the general practictioner of the patient 15 months after the trial to obtain survival data.	status will be checked 15 months after surgery

Collaborators and Investigators

• Sponsor: Erasmus Medical Center
• Collaborators: Stichting Coolsingel

Publications and helpful links

General Publications

• Incekara F, Smits M, Dirven L, Bos EM, Balvers RK, Haitsma IK, Schouten JW, Vincent AJPE. Intraoperative B-Mode Ultrasound Guided Surgery and the Extent of Glioblastoma Resection: A Randomized Controlled Trial. Front Oncol. 2021 May 19;11:649797. doi: 10.3389/fonc.2021.649797. eCollection 2021.

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2016
• Primary Completion (Actual): December 31, 2019
• Study Completion (Anticipated): August 1, 2020

Study Registration Dates

• First Submitted: November 2, 2017
• First Submitted That Met QC Criteria: May 9, 2018
• First Posted (Actual): May 21, 2018

Study Record Updates

• Last Update Posted (Actual): January 13, 2020
• Last Update Submitted That Met QC Criteria: January 9, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: Glioma, intraoperative ultrasound, gross total resection, quality of life
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioma
• Other Study ID Numbers: MEC-2015-46

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No