Prospective Phase II Study of Radiotherapy Dose Escalation in Grade 4 Glioma Using ⁶⁸Ga-Pentixafor PET Scan

Area of Science:

• Neuro-oncology
• Radiation Oncology
• Nuclear Medicine

Background:

• Local failure is a significant challenge in treating high-grade gliomas, including glioblastoma (GBM).
• A dose-response relationship for radiotherapy (RT) in GBM has been suggested by pilot studies.
• ⁶⁸Ga-Pentixafor PET scans show promise for precise tumor delineation in glioma.

Purpose of the Study:

• To evaluate the feasibility and safety of dose-escalated radiotherapy guided by ⁶⁸Ga-Pentixafor PET in patients with grade 4 glioma.
• To assess the impact of this approach on overall survival (OS) and progression-free survival (PFS).
• To determine the incidence of radiation necrosis as a secondary endpoint.

Main Methods:

• A prospective Phase II study included 30 patients with biopsy-proven grade 4 glioma.
• Radiotherapy was planned in two phases with a simultaneous integrated boost (SIB) to PET-avid areas, escalating the dose to 67 Gy.
• ⁶⁸Ga-Pentixafor PET scans were used for precise tumor delineation, alongside MRI and standard treatment protocols including temozolomide.

Main Results:

• Analysis of 30 patients revealed a median OS of 23 months (1, 2, and 3-year OS: 90%, 40%, 17.8%).
• Extent of surgery and Karnofsky performance status were significantly associated with OS (p=0.04 and p=0.007, respectively).
• No patients experienced significant radiation necrosis, indicating good treatment tolerability.

Conclusions:

• Dose-escalated radiotherapy guided by ⁶⁸Ga-Pentixafor PET did not demonstrate a survival benefit in this study.
• The treatment regimen was well-tolerated, with no observed radiation necrosis.
• Further research with larger sample sizes is warranted to explore the potential of ⁶⁸Ga-Pentixafor PET in guiding RT dose escalation for GBM.