What is the impact of follow-up MRI scans on treatment decisions in patients with a glioblastoma?

imaging neurology Glioblastoma

prof. dr. R.A. Dierckx
dr. A van der Hoorn
dr. P.J. van Laar
dr. R.H. Enting

Nature of the research:
This research will be conducted at the department of radiology and neurology in the UMCG. The current project is embedded in the research line: Diagnosis, treatment-planning and -evaluation in brain and head/neck tumours. This research line is one of the research lines of the Medical Imaging Center (MIC) in the UMCG (See also project description “Differentiation of tumour progression and treatment induced changes on imaging in patients with gliomas”. The current project is a retrospective database (imaging- and clinical data) study.

Fields of study:
neurology oncology radiology

Background / introduction
Glioblastomas are the most common primary brain tumour occurring in a relatively young population [1]. High-grade gliomas are accompanied by a high morbidity and mortality. Patients are initially treated by maximal resection of the tumour. However, the tumour is never completely removed due to its infiltrative nature and the risk of damaging healthy brain tissue during resection. Glioblastomas therefore have high recurrence rates and local recurrence is inevitable [2]. Patients receive additional radiotherapy and chemotherapy to eradicate as much of the residual tumour as possible [3]. However, this extensive and lengthy therapy does not prevent tumour recurrence, meaning that patients need to be monitored and undergo regular follow-up scanning to assess disease progression.

To monitor the treatment and the occurrence of recurrence, standard scanning moments are currently performed, although no formal advise has been formulated in the Dutch guidelines [4]. MRI follow-up is done directly postoperative (<72 hours after surgery), post-radiotherapy, 4 months post-radiotherapy, and 7 months post-radiotherapy [4]. These MRI scans are planned ahead and performed even if the patient is asymptomatic. Unplanned MRI scans are performed in symptomatic patients to exclude or confirm disease progression. However, MRI results do not always provide clarity on the nature of an abnormality as they cannot differentiate between tumour tissue or imaging changes caused by therapy [5]. Both result in a leakage of the blood-brain-barrier, visible as contrast enhancement on post contrast T1-weighted MRI scans. More advanced MRI techniques can be performed to look at the cellularity, the perfusion and metabolites of the abnormal area [5]. However, a definitive differentiation between disease progression and imaging changes caused by therapy remains difficult [4,6]. This is problematic for both the patient and physician.

Therefore, one may question the impact of the MRI follow-up scans on treatment decisions (see for example figure 1). Also, there is no available standard second-line therapy for patients with recurrent disease. These patients may undergo re-resection or participate in a clinical trial. However, none of these options are curative and prognosis remains poor. Follow-up scans that demonstrate to be of little clinical value as treatment decision would not be altered, could possibly be omitted in the standard follow-up regime. This would, decrease medical costs and patient burden.

However, the impact of the standard follow-up MRI scheme on the treatment decisions in glioblastoma patients is unknown. This study aims to assess the impact by analysing the MRI follow-up scans of glioblastoma patients treated in the UMCG in asymptomatic and symptomatic cases.
Research question / problem definition
What is the impact of the MRI follow-up scans on the treatment decisions in patients with a glioblastoma?
The first foundation of this retrospective project is already in place. A non-WMO statement has been given by the medical ethical committee. Currently, we have created the forms (CRF) that needed to be filled in for each subject. All patients with glioblastoma that have been treated in the UMCG and have not objected to use their data for research purposes have been identified.

Patients inclusion criteria are:
- Diagnosis of glioblastoma (Glioma WHO Grade IV).
- Older than 18 years of age at diagnosis.
- No history of previous brain tumour, cranial radiotherapy, or brain surgery.
- Available follow-up MRI scans.

The student will start with checking the selected patient against the patients inclusion criteria. In the next phase, patients’ data will be collected via PoliPlus. Afterwards, the analysis of the data will be performed by the student. Due to the retrospective nature of this study, it can be planned flexible although a sufficient amount of time is required. For motivated students, there will be opportunities to continue to perform research within this area (for example, MD PhD project)..

To acquire a clinical view on the patients involved in this research, it will be possible for the student to join the neurologist at the outpatient department. Joining the neuro-radiologist during MRI scanning and reporting is also possible. Joining the weekly neuro-oncology multidisciplinary meeting on Wednesdays furthers adds to the clinical knowledge within this research subject.
1. Burnet NG, Jefferies SJ, Benson RJ, et al. Years of life lost (YLL) from cancer is an important measure of population burden and should be considered when allocating research funds. Br J Cancer 2005;92:241-245.
2. Brandsma D, Stalpers T, Taal W et al. Clinical features, mechanisms, and management of pseudoprogression in malignant gliomas. Lancet Oncol 2008;9(5):453-61.
3. Stupp R, Mason WP, van den Bent MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 2005;352:987-996.
4. Landelijke werkgroep Neuro-oncologie. Richtlijn Neuro-oncologie beelvormende diagnositiek versie 3.0. [Internet] . Nederland; Integraal Kanker centrum. 2015-04-15 [ Updated 2015-04-15, cited 207-01-05]. Available from: pagina.php&id=38071&richtlijn_id=963&tab=1
5. Dhermain FG, Hau P, Lanfermann H et al. Advanced MRI and PET imaging for assessment of treatment response in patients with gliomas. Lancet Neurol 2010;9:906-920.
6. Price SJ. The role of advanced MR imaging in understanding brain tumour pathology. Br J Neurosurg 2007;21:562-575.
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