Application of FET-PET in Fusion With MRI in the Treatment of Glioblastoma Multiforme [TYR-GLIO]

NCT06466031 | Recruiting

• 1 other identifier: 2023/ABM/01/00010
• Study Type: interventional
• Target: 189
• Locations: 1 country
• Sites: 1

Brief Summary

Glioblastoma multiforme (GBM WHO IV) is the most common and aggressive primary brain tumor in adults, carrying a poor prognosis with a median survival of 12-16 months. The annual incidence is approximately 5 per 100,000 (roughly 600 cases annually in Poland), predominantly affecting individuals in their prime productive years. The standard of care consists of maximal safe resection followed by the Stupp protocol (60 Gy fractionated radiotherapy and temozolomide chemotherapy). Routine surgical management relies on contrast-enhanced MRI. Gross total resection (GTR) is defined as the complete removal of the contrast-enhancing lesion. Although GTR improves progression-free survival (PFS) and overall survival (OS), local recurrence at the operative site occurs in up to 51% of patients within a year. This rapid regrowth is driven by glioblastoma stem cells infiltrating the surrounding non-enhancing brain tissue. Consequently, standard contrast-enhanced MRI lacks the sensitivity required to define true tumor boundaries for optimal patient outcomes. To overcome this, positron emission tomography (PET-CT) using amino acid tracers like 18F-fluoroethyl-L-tyrosine (18F-FET) offers a promising alternative. Unlike 18-FDG, which is obscured by physiologically high glucose uptake in healthy brain tissue, 18F-FET provides high specificity and sensitivity for glial tumors. Crucially, studies show that MRI contrast enhancement overlaps with only 58% of the hypermetabolic area identified by 18F-FET. While "supramarginal" resections based on FLAIR MRI abnormalities (assumed to contain infiltrating stem cells) improve PFS by roughly 2 months, the FLAIR sequence cannot definitively distinguish active tumor infiltration from standard peritumoral edema. This proposed experiment carries significant innovative value: it aims to use the fusion of 18F-FET PET and contrast-enhanced MRI to precisely guide both primary surgical resection and postoperative radiotherapy. By redefining the primary target volume to include the area of true biological tumor activity rather than just the MRI-enhancing mass (incorporating it into GTV, CTV, and PTV planning), the procedure directly targets residual glioblastoma stem cells. While PET has been evaluated for radiotherapy planning in recurrent GBM, high-quality data regarding its use for primary surgical planning is lacking. This study aims to fill that crucial gap in the literature.

Conditions

Glioblastoma Multiforme

Keywords

Glioblastoma Multiforme; Methionine; Positron-Emission Tomography; Brain neoplasms; Progression-free survival; Dose Fractionation, Radiation; Post-surgical radiotherapy

Outcome Measures

Primary Outcomes (2)

• Progression-free survival

  36 months post surgery

• Overall survival

  36 months post surgery

Secondary Outcomes (5)

• Assessment of tumor volume (GTV) in MRI with contrast in relation to the tumor borders in PET-CT

  1 day before radiotherapy

• Volumetric assessment of the planned radiotherapy volume based on PET-MRI and MRI planning.

  1 day before radiotherapy

• Long-term survival rate and prognostic factors (longer than 1 year from diagnosis).

  36 months post surgery

• Pattern of local recurrence based on postoperative PET-MRI. Assessment of the nature and location of local recurrence based on the postoperative SUV parameter FET-PET and MRI examination.

  36 months post surgery

• Assessment of quality of life related (SF-36 questionnaire) to the increase in the volume of the tumor undergoing treatment.

  7 days post surgery, 1 day before and after radiotherapy

Study Arms (3)

Resection and radiotherapy according to the MRI & PET fusion

EXPERIMENTAL

Surgical treatment and radiotherapy planned based on FET-PET and MRI+T1C fusion.

Other: MRI & PET fusion

Radiotherapy according to the MRI & PET fusion

EXPERIMENTAL

Surgical treatment planned based on MRI+T1C study, radiotherapy planned based on FET-PET and MRI+T1C fusion.

Other: MRI & PET fusion; Other: MRI+T1C

Resection and radiotherapy according to the MRI

SHAM COMPARATOR

Surgical treatment and radiotherapy planned based on MRI+T1C.

Other: MRI+T1C

Interventions

MRI & PET fusion OTHER

MRI+T1C in fusion with FET-PET will be used for tumor resection and/or radiotherapy planning. Resection will be terminated after removal of PET-assigned tumor margin or in case any neuromonitoring-based indications regarding neurological damage occur.

Radiotherapy according to the MRI & PET fusion; Resection and radiotherapy according to the MRI & PET fusion

MRI+T1C OTHER

MRI+T1C will be used for tumor resection and radiotherapy planning. Resection will be terminated after removal of contrast-enhancing part regardless of 5-ALA fluorescence or in case any neuromonitoring-based indications regarding neurological damage occur.

Radiotherapy according to the MRI & PET fusion; Resection and radiotherapy according to the MRI

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Copernicus Memorial Hospital: lead
• Medical Research Agency, Poland: collaborator

Study Sites (1)

Copernicus Memorial Hospital in Łódź, Poland

Lodz, Łódź Voivodeship, 93-513, Poland

RECRUITING

Related Publications (11)

• Hutterer M, Nowosielski M, Putzer D, Jansen NL, Seiz M, Schocke M, McCoy M, Gobel G, la Fougere C, Virgolini IJ, Trinka E, Jacobs AH, Stockhammer G. [18F]-fluoro-ethyl-L-tyrosine PET: a valuable diagnostic tool in neuro-oncology, but not all that glitters is glioma. Neuro Oncol. 2013 Mar;15(3):341-51. doi: 10.1093/neuonc/nos300. Epub 2013 Jan 17.

  PMID: 23335162 BACKGROUND

• Dunet V, Pomoni A, Hottinger A, Nicod-Lalonde M, Prior JO. Performance of 18F-FET versus 18F-FDG-PET for the diagnosis and grading of brain tumors: systematic review and meta-analysis. Neuro Oncol. 2016 Mar;18(3):426-34. doi: 10.1093/neuonc/nov148. Epub 2015 Aug 4.

  PMID: 26243791 BACKGROUND

• Robert JA, Leclerc A, Ducloie M, Emery E, Agostini D, Vigne J. Contribution of [18F]FET PET in the Management of Gliomas, from Diagnosis to Follow-Up: A Review. Pharmaceuticals (Basel). 2024 Sep 18;17(9):1228. doi: 10.3390/ph17091228.

  PMID: 39338390 BACKGROUND

• Ort J, Hamou HA, Kernbach JM, Hakvoort K, Blume C, Lohmann P, Galldiks N, Heiland DH, Mottaghy FM, Clusmann H, Neuloh G, Langen KJ, Delev D. 18F-FET-PET-guided gross total resection improves overall survival in patients with WHO grade III/IV glioma: moving towards a multimodal imaging-guided resection. J Neurooncol. 2021 Oct;155(1):71-80. doi: 10.1007/s11060-021-03844-1. Epub 2021 Oct 1.

  PMID: 34599479 BACKGROUND

• Harat M, Rakowska J, Harat M, Szylberg T, Furtak J, Miechowicz I, Malkowski B. Combining amino acid PET and MRI imaging increases accuracy to define malignant areas in adult glioma. Nat Commun. 2023 Jul 29;14(1):4572. doi: 10.1038/s41467-023-39731-8.

  PMID: 37516762 BACKGROUND

• Herholz K, Holzer T, Bauer B, Schroder R, Voges J, Ernestus RI, Mendoza G, Weber-Luxenburger G, Lottgen J, Thiel A, Wienhard K, Heiss WD. 11C-methionine PET for differential diagnosis of low-grade gliomas. Neurology. 1998 May;50(5):1316-22. doi: 10.1212/wnl.50.5.1316.

  PMID: 9595980 BACKGROUND

• Kracht LW, Miletic H, Busch S, Jacobs AH, Voges J, Hoevels M, Klein JC, Herholz K, Heiss WD. Delineation of brain tumor extent with [11C]L-methionine positron emission tomography: local comparison with stereotactic histopathology. Clin Cancer Res. 2004 Nov 1;10(21):7163-70. doi: 10.1158/1078-0432.CCR-04-0262.

  PMID: 15534088 BACKGROUND

• Singhal T, Narayanan TK, Jain V, Mukherjee J, Mantil J. 11C-L-methionine positron emission tomography in the clinical management of cerebral gliomas. Mol Imaging Biol. 2008 Jan-Feb;10(1):1-18. doi: 10.1007/s11307-007-0115-2. Epub 2007 Oct 24.

  PMID: 17957408 BACKGROUND

• Grosu AL, Weber WA, Riedel E, Jeremic B, Nieder C, Franz M, Gumprecht H, Jaeger R, Schwaiger M, Molls M. L-(methyl-11C) methionine positron emission tomography for target delineation in resected high-grade gliomas before radiotherapy. Int J Radiat Oncol Biol Phys. 2005 Sep 1;63(1):64-74. doi: 10.1016/j.ijrobp.2005.01.045.

  PMID: 16111573 BACKGROUND

• Galldiks N, Niyazi M, Grosu AL, Kocher M, Langen KJ, Law I, Minniti G, Kim MM, Tsien C, Dhermain F, Soffietti R, Mehta MP, Weller M, Tonn JC. Contribution of PET imaging to radiotherapy planning and monitoring in glioma patients - a report of the PET/RANO group. Neuro Oncol. 2021 Jun 1;23(6):881-893. doi: 10.1093/neuonc/noab013.

  PMID: 33538838 BACKGROUND

• Pirotte B, Goldman S, Dewitte O, Massager N, Wikler D, Lefranc F, Ben Taib NO, Rorive S, David P, Brotchi J, Levivier M. Integrated positron emission tomography and magnetic resonance imaging-guided resection of brain tumors: a report of 103 consecutive procedures. J Neurosurg. 2006 Feb;104(2):238-53. doi: 10.3171/jns.2006.104.2.238.

  PMID: 16509498 BACKGROUND

MeSH Terms

Conditions

Glioblastoma; Brain Neoplasms

Interventions

Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques

Study Officials

• Kamil Krystkiewicz, PhD

  Department of Neurosurgery and Neurooncology, Copernicus Memorial Hospital in Łódź, Poland

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kamil Krystkiewicz, PhD

CONTACT

+48426895341; kamil.krystkiewicz@gmail.com

Marcin Tosik, PhD

CONTACT

+48426895341; sekretariat.neurochirurgia@kopernik.lodz.pl

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 2, 2024
• First Posted: June 20, 2024
• Study Start: December 8, 2025
• Primary Completion (Estimated): August 31, 2030
• Study Completion (Estimated): August 31, 2032
• Last Updated: April 17, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

PL (1)