Radiotherapy in Glioblastoma Multiforme: Evolution, Limitations, and Molecularly Guided Future

Area of Science:

• Neuro-oncology
• Radiation Oncology
• Medical Physics

Background:

• Glioblastoma multiforme (GBM) is an aggressive brain tumor with poor prognosis.
• Recurrence and treatment resistance are major challenges in GBM management.
• Radiotherapy (RT) is a cornerstone of GBM treatment.

Purpose of the Study:

• To review the evolution of RT techniques for GBM.
• To discuss current treatment guidelines and emerging therapies.
• To highlight challenges and future directions in GBM RT.

Main Methods:

• Review of historical and modern RT techniques (IMRT, VMAT).
• Analysis of standard treatment protocols (Stupp protocol) and adjuvant therapies (TTFields).
• Examination of factors contributing to recurrence and radioresistance (EGFR, PTEN, hypoxia, stem cells).

Main Results:

• The Stupp protocol with temozolomide (TMZ) improves overall survival (OS).
• Tumor Treating Fields (TTFields) further extend survival, especially in MGMT-methylated GBM.
• High recurrence rates within 2 cm of the irradiated field persist.

Conclusions:

• Advanced RT techniques and adjuvant therapies improve GBM outcomes.
• Tumor biology, hypoxia, and stem cells drive resistance and recurrence.
• Personalized RT strategies, novel agents, and advanced imaging are crucial for future progress.