Application of MET-PET in Fusion With MRI in the Treatment of Glioblastoma Multiforme

Glioblastoma multiforme (GBM IV WHO) is the most common, primary neoplasm of brain in the adults. Simultanously it is the most agressive one of all primary brain tumors. Despite the treatment the outcome in that group of patients is poor. In case of the optimal therapy the estimated median of survival ranges between 12 and 16 months. The present standard of treatment embraces the gross total resection with the preserved neurological functions and the posoperative management according to the Stupp's protocol (fractionated radiotherapy of 60 Gy dose and the chemotherapy with Temozolamide).

Annually the incidence rate of GBM is 5/100.000 of population. According to the National Tumor Registry 2494 people went down to the malignant neoplasmatic disease of brain classified as C71 (ICD-10) in 2020. The evaluation indicates that it is 600 new patients with the diagnosis of GBM. The disease becomes the 9th cause of death among males and the 13th one among females. The peak of incidence appears in the 5th decade of life and concerns the most productive population. Routinely the management embraces the planning of the resection surgery based on the preoperative magnetic resonance investigation (MRI) with contrast. The common image of the tumor allows to put the preliminary diagnosis with the high probability rate. The GBM occurs as the enhanced tumor with the central necrosis and the circumferential brain edema visible in T2 and Flair sequences of MRI. Commonly the border of tumor becomes the line of contrast enhancement. The enhances area is the aim of surgical treatment. The lack of the preoperative enhanced area in the postoperative MRI is assumed as the gross total resection (GTR). It has been proved that the range of the resection translates into the overall survival (OS) and the progression free survival (PFS). Despite the resection classified as GTR the relapse in the operated area often occurs. It can be explained by the presence of the glioma stem cells in the surrounding neuronal tissue. They are responsible for the early relapse of GBM. Notably, it is evident that the MRI with contrast becomes the method which does not reveal the proper range of resection with the relevant sensitivity so as to extend PFS and OS. The positron emission tomography (PET) is one of the diagnostic methods having been clinically evaluated. PET assesses the metabolic demand of the neoplasm for the biochemical substrates. That methodology is commonly used in case of severity of the solid tumors. The fluorodeoxyglucose (18-FDG) is the most frequently used. However the high metabolism of glucose within the brain, particularly in the grey matter, 18-FDG has the limitation in the process of planning of the tumor resection. The higher specificity and sensitivity are elicited among the markers including aminoacids, praticularly 11-C methionine (11C-MET). Within the gliomas the higher uptake is observed than in the healthy brain. The range of the contrast enhancement in the MRI covers only 58% of the higher 11C-MET metabolism. Comparing these results with a tumor resection beyond the enhancement area, indicates the necessity of the precise assessment of the proposed method in the routine planning of the glioma resection.

Current body of literature lacks in high quality research concerning that issue. The articles regarding the glioma resection beyond the GTR may be found instead. The surgery is limited to the resection of brain area with the incorrect signal in the FLAIR sequence, suspected of the presence of glioma stem cells. The described technique allows to extend PFS by for about 2 months. In that case the resection is based mainly on the FLAIR sequence which does not determine the presence of the neoplasm therein. The fusion of the MRI and the MET-PET images would allow to plan the resection so as to cover the area of incorrectly increased marker uptake.


Eligibility Criteria:
Inclusion Criteria:

* Single macroscopic tumor focus with the appearance of glioblastoma multiforme on MRI with contrast - contrast-enhancing lesion, completely or with central necrosis, with surrounding edema.
* No history of cancer in other organs. No suspicious lesions on X-ray of the chest and abdomen (CT with contrast).
* No clinical suspicion of brain abscess - no meningeal symptoms, signs of neuroinfection, fever, elevated inflammatory parameters.
* Primary tumor, without neurosurgical, radiotherapy or oncology intervention. Prior tumor biopsy is allowed.
* Tumor eligible for surgical treatment - craniotomy and tumor resection.
* Age ≥ 18 years but \< 70 years old.
* Quality of life assessment: KPS ≥ 70.
* Informed patient consent to the study and proposed treatment.
* No allergy to contrast agents used in PET and MRI.
* No medical contraindications to neurosurgery - craniotomy and resection.

Exclusion Criteria:

* Multifocal brain tumor.
* Recurrence of glioblastoma multiforme.
* Clinical or radiological suspicion of brain metastasis or brain abscess.
* Postoperative histopathological diagnosis other than WHO grade IV glioblastoma.
* Medical contraindications to any surgery under general anesthesia.
* Pregnancy, breastfeeding.
* Known allergy to gadolinium contrast or radiopharmaceutical tracing agent.