Achieving a Better Outcome Through Limiting the Glioblastoma Clinical Target Volume (BELGICA)

Impact of Reducing the Irradiation Volume on Survival, Toxicity, and Quality of Life in Patients With Glioblastoma Treated With Radiochemotherapy: a Prospective Multicenter Randomised Study

The objective of the BELGICA trial is to evaluate if radiotherapy could be given in a more focused manner in patients with glioblastoma in order to reduce side effects and improve quality of life.

The glioblastoma (GBM) is the most common and aggressive tumour originating from the brain, affecting approximately 600 patients per year in Belgium. The treatment consists in surgical resection of the tumour (when feasible), followed by a combination of radiotherapy and chemotherapy. Despite multimodal treatment (surgery, radiotherapy, and chemotherapy), the life expectancy of patients with GBM remains limited, with an average survival of 12-18 months and only 5% of patients surviving more than 5 years. In addition to limited survival, most patients with GBM experience impaired quality of life, both because of the disease and treatments.

Radiotherapy is a treatment where radiation is used to kill cancer cells. In GBM, radiotherapy is targeted at the tumour (or tumour bed if the tumour was resected) with a safety margin around it (the "Clinical Target Volume" or CTV) to account for potential microscopic spread of the tumour. The downside of this safety margin is that a substantial amount of brain tissue is irradiated, which can lead to treatment toxicity. Reducing the CTV margin would enable to decrease the volume of brain being irradiated and could thereby allow to reduce the side effects of brain irradiation.

The BELGICA trial (Achieving a BEtter outcome through Limiting the GlIoblastoma Clinical tArget volume) is a national multicentre trial which will evaluate if reducing the irradiation volume in glioblastoma is safe and allows for lowering side effects and improving quality of life.

Study Overview

• Status: Recruiting
• Conditions: Glioblastoma; Radiotherapy Side Effect
• Intervention / Treatment: Radiation: Radiotherapy (CTV=15mm); Radiation: Radiotherapy (CTV=10mm)

Detailed Description

INDICATION :

Patients with newly diagnosed glioblastoma for whom radiochemotherapy is indicated

RATIONALE :

Glioblastoma is the most frequent primary malignant brain tumour, annually affecting approximately 600 patients in Belgium.

The current management of glioblastoma includes surgical resection (when feasible), followed by radiotherapy (RT) and chemotherapy. Despite this multimodal treatment, the prognosis of patients with glioblastoma is dismal with a median overall survival of approximately 1 year.

In addition to poor survival, patients with glioblastoma face several symptoms, notably cognitive decline and deterioration in quality of life (QOL), which are both resulting from the disease evolution and the treatments. Given the limited life expectancy of these patients, improvement of well-being during the remaining survival period is essential and is a major concern for glioblastoma patients and their relatives.

In glioblastoma, radiotherapy is targeted at the tumour (or tumour bed after resection) with a safety margin around it (i.e., the "Clinical Target Volume" or CTV) to account for potential microscopic extension of the tumour. The downside of this safety margin is that a substantial amount of normal brain tissue is irradiated, which can lead to treatment toxicity. Reducing the CTV margin would enable to decrease the volume of brain being irradiated and could thereby allow to reduce the side effects of brain irradiation.

Current European guidelines in glioblastoma recommend a clinical target volume (CTV) margin of 15 mm around the tumour. However, the optimal target volume is still unknown, mainly based on historical practices, and different margins have been used in clinical practice.

The BELGICA trial will prospectively evaluate if reducing the CTV margin from 15 to 10 mm allows for improving the toxicity profile of the treatment without compromising the outcome.

This intervention is expected to be safe and to reduce toxicity based on available clinical data.

Target volume reduction in glioblastoma Several retrospective or prospective non-randomized series of patients treated with a <= 10 mm CTV margin showed local control and survival outcomes similar to those of patients treated with larger margins, which supports the safety of the intervention. Similarly, pattern of recurrence analysis in patients treated with a >= 15 mm CTV suggests that using a 10 mm CTV margin would not lead to more recurrences.

Relation between radiation dose and toxicity in glioblastoma Current clinical data in patients with glioblastoma show that lower radiation dose to surrounding normal brain structures is associated with lower cognitive decline, improved QOL, reduced toxicity and fatigue.

Glioblastoma, radiotherapy, and cognitive decline Most patients with glioblastoma present with neurocognitive dysfunction at the time of diagnosis and will experience further progressive decline during the clinical course of the disease. This occurs early, with a median time to deterioration of approximately 1 months .

Neurocognitive decline is multifactorial, due to tumour-, patient-, and treatment-related factors.

Cranial irradiation is associated with cognitive toxicity. In patients with brain metastases, strategies aiming to reduce the radiation dose to the surrounding brain structures have allowed to reduce the rate of cognitive decline, e.g. hippocampal-avoidance in patients receiving whole-brain radiotherapy.

By reducing the irradiation volume in patients with glioblastoma, the dose to the surrounding brain structures will be lowered, potentially reducing the rate of cognitive decline.

METHODS :

The BELGICA trial will include 347 patients in Belgium with newly diagnosed glioblastoma. The patients will be randomized 1:1 into two groups. The experimental group will receive a radiotherapy with a reduced irradiation volume (CTV 10mm). The control group will receive radiotherapy with standard irradiation volume (CTV 15mm). In both groups, patients will receive temozolomide chemotherapy in association with radiotherapy. Stratification factors are: age (under/above 70 years), MGMT promotor methylation status (methylated/unmethylated/unknown), and extent of resection.

• Study Type: Interventional
• Enrollment (Estimated): 347
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Dario Di Perri, MD; Phone Number: +32 2 764 47 52; Email: dario.diperri@saintluc.uclouvain.be
• Study Contact Backup: Name: Chloë De Laet; Phone Number: +32 2 764 82 75; Email: Belgica.kce@saintluc.uclouvain.be

Study Locations

• Belgium
  • Aalst, Belgium, 9300
    • Not yet recruiting
    • Olv Azorg
    • Principal Investigator: Samuel Bral, MD
    • Sub-Investigator: Benedikt Engels, MD
    • Contact: Secretary office; Phone Number: +32 53 72 86 66; Email: radiotherapie@azorg.be
  • Baudour, Belgium, 7331
    • Recruiting
    • EpiCURA
    • Contact: Secretary office; Phone Number: +32 65 61 44 86
    • Principal Investigator: Serge Ndam, MD
  • Bruges, Belgium, 8000
    • Recruiting
    • AZ Sint Jan
    • Contact: Secretary office; Phone Number: +32 50 45 28 00; Email: radiotherapie.brugge@azsintjan.be
    • Principal Investigator: Martijn Swimberghe, MD
  • Brussels, Belgium, 1200
    • Recruiting
    • Cliniques Universitaires Saint-Luc
    • Contact: Secretary office; Phone Number: +32 2 764 47 52
    • Principal Investigator: Dario Di Perri, MD
    • Sub-Investigator: Nicolas Whenham, MD
  • Brussels, Belgium, 1090
    • Not yet recruiting
    • UZ Brussel
    • Contact: Secretary office; Phone Number: +32 2 477 60 41; Email: balie-radiotherapie@uzbrussel.be
    • Principal Investigator: Selma Ben Mustapha, MD
  • Brussels, Belgium, 1070
    • Not yet recruiting
    • Institut Jules Bordet
    • Contact: Secretary office; Phone Number: +32 2 541 38 00; Email: accueil.cons.radiotherapie@hubruxelles.be
    • Principal Investigator: Philippe Martinive, MD
  • Genk, Belgium, 3600
    • Recruiting
    • Ziekenhuis Oost-Limburg (ZOL)
    • Contact: Secretary office; Phone Number: +32 89 80 83 30
    • Principal Investigator: Mieke Govers, MD
    • Sub-Investigator: Annelies Maes, MD
    • Sub-Investigator: Anne-Sophe Van de Velde, MD
  • Ghent, Belgium, 9000
    • Recruiting
    • AZ Sint-Lucas
    • Contact: Secretary office; Phone Number: +32 9 224 66 20; Email: secretariaat.radonco@azstlucas.be
    • Principal Investigator: Wim Duthoy
  • Ghent, Belgium, 9000
    • Not yet recruiting
    • UZ Gent
    • Contact: Secretary office; Phone Number: +32 9 332 30 15; Email: secretariaat.radiotherapie@uzgent.be
    • Principal Investigator: Tom Boterberg, MD
  • Gilly, Belgium, 6060
    • Recruiting
    • Grand Hôpital de Charleroi
    • Contact: Secretary office; Phone Number: +32 60 11 12 13
    • Principal Investigator: Benjamin Ledoux, MD
  • Hasselt, Belgium, 3500
    • Recruiting
    • Jessa Ziekenhuis
    • Sub-Investigator: Mieke Govers, MD
    • Sub-Investigator: Annelies Maes, MD
    • Contact: Secretary office; Phone Number: +32 11 33 79 79
    • Principal Investigator: Anne-Sophe Van de Velde, MD
  • Kortrijk, Belgium, 8500
    • Recruiting
    • Az Groeninge
    • Contact: Secretary office; Phone Number: +32 56 63 39 03; Email: radiotherapie@azgroeninge.be
    • Principal Investigator: Nick Liefhooghe, MD
    • Sub-Investigator: Isabelle Kindts, MD
  • La Louvière, Belgium, 7100
    • Recruiting
    • CHU Helora
    • Contact: Secretary office; Phone Number: +32 64 23 41 88
    • Principal Investigator: Samuel Palumbo, MD
  • Leuven, Belgium, 3000
    • Recruiting
    • UZ Leuven
    • Contact: Secretary office; Phone Number: +32 16 34 76 00
    • Principal Investigator: Maarten Lambrecht, MD
  • Liège, Belgium, 4000
    • Recruiting
    • Chu Liege
    • Contact: Secretary office; Phone Number: +32 4 323 75 96; Email: radiotherapie@chuliege.be
    • Principal Investigator: Lisa Grandjean, MD
  • Mechelen, Belgium, 2800
    • Recruiting
    • Az Sint Maarten
    • Contact: Secretary office; Phone Number: +32 15 89 29 80
    • Principal Investigator: Julie Van der Veen, MD
    • Sub-Investigator: Valerie Vandeputte, MD
  • Montigny-le-Tilleul, Belgium, 6110
    • Recruiting
    • Hôpital André Vésale - HUmani
    • Contact: Secretary Office; Phone Number: +32 71 92 09 52
    • Principal Investigator: Martin Manderlier, MD
    • Sub-Investigator: Pauline Semoulin, MD
  • Mouscron, Belgium, 7700
    • Not yet recruiting
    • CH Mouscron
    • Contact: Secretary office; Phone Number: +32 56 85 83 60; Email: secretariat.radiotherapie@chmouscron.be
    • Principal Investigator: Katrien Thevissen, MD
    • Sub-Investigator: Anne-Emmanuelle Yeo, MD
  • Namur, Belgium, 5000
    • Recruiting
    • CHU UCL Namur - Sainte Elisabeth
    • Contact: Secretary office; Phone Number: +32 81 72 05 25
    • Principal Investigator: Marie Wanet, MD
  • Roeselare, Belgium, 8800
    • Recruiting
    • AZ Delta
    • Contact: Secretary office; Phone Number: +32 51 23 75 82
    • Principal Investigator: Caroline Sweldens, MD
    • Sub-Investigator: Lien Van De Voorde, MD
  • Uccle, Belgium, 1180
    • Recruiting
    • Cliniques de l'Europe
    • Contact: Secretary office (Sainte Elisabeth); Phone Number: +32 2 614 25 40
    • Contact: Secretary office (Saint Michel); Phone Number: +32 2 614 37 26
    • Principal Investigator: Dorothée Berben, MD
  • Verviers, Belgium, 4800
    • Recruiting
    • CHR Verviers
    • Contact: Secretary office; Phone Number: +32 87 21 24 22
    • Principal Investigator: David Devillers, MD
  • Wilrijk, Belgium, 2610
    • Recruiting
    • ZAS Augustinus
    • Contact: Secretary office; Phone Number: +32 3 443 37 37; Email: secretariaat@iridiumnetwerk.be
    • Principal Investigator: Carole Mercier, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participants capable of giving informed consent
• Age >= 18 y.o.
• WHO performance status 0-2
• Newly diagnosed glioblastoma (Histologically proven glioblastoma per WHO 2021 classification based on biopsy or resection )
• Indication of chemoradiotherapy confirmed by multidisciplinary tumour board

Exclusion Criteria:

• Participation in a competing trial
• Known contraindication to undergo MRI scans

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
Active Comparator: Standard of Care	Radiation: Radiotherapy (CTV=15mm); Radiotherapy with standard irradiation volume CTV=15mm
Experimental: Interventional arm	Radiation: Radiotherapy (CTV=10mm); Radiotherapy with reduced irradiation volume CTV=10mm

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Number of days from date of randomization to the date of death due to any cause	From randomization to the end of the study

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neurocognitive functioning	Hopkins verbal learning test revised; Trail Marking Test A & B; Controlled Oral Word Association Test	at baseline, 1 month after radiotherapy and at 1 year
Radiation-induced toxicity	Assessment of fatigue, headache, nausea, alopecia and radiatio dermatitis according to the CTCAE assessment score. Score ranges from Grade 1 to Grade 5, with higher grades resulting in more severe symptoms.	From enrollment until end of follow-up (2 years)
Health-related Quality of Life	EQ-5D-5L; QLQ-C30; QLQ-BN20	From enrollment until end of follow-up (2 years)
Progression-free survival	Length of time during and after treatment for a disease, such as cancer, that a patient lives with the disease without it worsening	From randomization until end of follow-up (2 years)
Pattern of recurrence	(in case of progression) Manner in which the tumor returns after a period of improvement or remission. It often involves tracking the frequency, timing, and location of the tumor's return	From randomization until end of follow-up (2 years)
Anti-edema therapy	Recording of the needs of anti-edema therapy	From randomization until end of follow-up (2 years)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Normal tissue complication probability model (NTCP)	To develop a normal tissue complication probability model (NTCP) for radiation-induced cognitive toxicity, based on clinical and dosimetric measures (e.g. radiation dose delivered to brain structures)	From enrollment until end of follow-up (2 years)

Collaborators and Investigators

• Sponsor: Cliniques universitaires Saint-Luc- Université Catholique de Louvain
• Collaborators: Belgium Health Care Knowledge Centre
• Investigators: Principal Investigator: Dario Di Perri, MD, Cliniques universitaires Saint-Luc- Université Catholique de Louvain

Study record dates

Study Major Dates

• Study Start (Actual): May 12, 2025
• Primary Completion (Estimated): October 1, 2031
• Study Completion (Estimated): October 1, 2031

Study Registration Dates

• First Submitted: November 15, 2024
• First Submitted That Met QC Criteria: December 3, 2024
• First Posted (Actual): December 5, 2024

Study Record Updates

• Last Update Posted (Actual): February 27, 2026
• Last Update Submitted That Met QC Criteria: February 24, 2026
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Wounds and Injuries; Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Radiation Injuries; Therapeutics; Radiotherapy
• Other Study ID Numbers: KCE23-1426

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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