Post-Operative Accelerated-Hypofractionated Chemoradiation With Volumetric Modulated Arc Therapy and Simultaneous...

Area of Science:

• Radiation Oncology
• Neuro-oncology
• Clinical Trials

Background:

• Glioblastoma Multiforme (GBM) is an aggressive primary brain cancer with poor prognosis.
• Modern radiotherapy (RT) techniques offer potential for dose escalation in GBM treatment.
• Volumetric Modulated Arc RT with Simultaneous Integrated Boost (VMAT-SIB) allows precise dose delivery.

Purpose of the Study:

• To define the adjuvant maximum tolerated dose (MTD) for GBM using VMAT-SIB.
• To evaluate VMAT-SIB combined with standard dose temozolomide (TMZ) in resected GBM patients.
• To establish safe dose limits for accelerated hypofractionated RT in GBM.

Main Methods:

• Phase I clinical trial involving 37 operated GBM patients.
• VMAT-SIB technique delivered RT in 25 fractions over 5 weeks.
• Dose escalation in Planning Target Volume 1 (PTV1) from 72.5 Gy to 85 Gy; PTV2 fixed at 45 Gy.
• Concurrent and sequential temozolomide (TMZ) administered per EORTC/NCIC protocol.
• Dose-limiting toxicities (DLTs) assessed using RTOG and RTOG-EORTC scales.

Main Results:

• Thirty-seven patients were enrolled, with dose levels ranging from 72.5 Gy to 82.5 Gy.
• The maximum tolerated dose (MTD) was determined to be 80 Gy in 25 fractions.
• Three patients (8.1%) experienced Grade ≥ 3 acute neurological toxicities at higher dose levels.
• Two dose-limiting toxicities (DLTs) occurred at 82.5 Gy, leading to trial closure at 80 Gy MTD.
• Two asymptomatic radionecrosis cases were documented.

Conclusions:

• 80 Gy in 25 fractions of accelerated hypofractionated RT is the MTD for resected GBM.
• VMAT-SIB combined with standard dose TMZ is a feasible treatment approach for GBM.
• This dose level provides a basis for future efficacy studies in GBM.