Achieving a Better Outcome Through Limiting the Glioblastoma Clinical Target Volume
- Conditions
- GlioblastomaRadiotherapy Side Effect
- Registration Number
- NCT06719440
- Lead Sponsor
- Cliniques universitaires Saint-Luc- Université Catholique de Louvain
- Brief Summary
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.
What is glioblastoma (GBM)? GBM is the most common and aggressive tumour originating from the brain, affecting approximately 600 patients per year in Belgium.
What is the current treatment for patients with GBM? The treatment consists in surgical resection of the tumour (when feasible), followed by a combination of radiotherapy and chemotherapy.
What is the outcome of patients with GBM? 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.
How is radiotherapy applied in GBM, and how could this be improved to decrease side effects and improve quality of life? 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.
What is the BELGICA trial? 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
- 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.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 347
-
• 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
-
• Participation in a competing trial
- Known contraindication to undergo MRI scans
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Primary Outcome Measures
Name Time Method Overall Survival From randomization until death of patient, assessed up to 26 months time until death
- Secondary Outcome Measures
Name Time Method Neurocognitive functioning from screening until follow-up, on average once per year Controlled Oral Word Association Test
HRQOL multiple timepoints QLQ-C30; QLQ-BN20; EQ-5D-5L
QLQ-C30 From Randomization to end of trial, assed up to 26 months Quality of life questionnaire. Points scale from 0 to 100. Higher score means higher response level.
QLQ-BN20 From Randomization to end of trial, assed up to 26 months Quality of life questionnaire. Points scale from 0 to 100. Higher score means higher symptomatic levels/more problems.
EQ-5D-5L From Randomization to end of trial, assed up to 26 months Quality of life questionnaire. Points scale from 0 to 100. Higher score means higher health level.
CTCAE assessment for radiation-induced toxicity From Randomization to end of trial, assed up to 26 months Assessment of fatigue, headache, nausea, alopecia and radiatio demratitis according to the CTCAE assessment score. Score ranges from Grade 1 to Grade 5, with higher grades resulting in more severe symptoms.