BIO-SHORT: Hypofractionated RT for Poor-Prognosis GBM

Condition(s) studied

Investigational drug(s) / intervention(s)

Standard radiotherapy using hypofractionated RT: Patients in the standard arm will undergo target volume delineation using conventional imaging. The initial clinical target volume (CTV-initial) will include the postoperative cavity, contrast-enhancing tumor on T1-weighted MRI, and gross disease. A 1-cm isotropic expansion, edited for anatomical barriers, will generate the CTV-final to account for infiltrative spread. The planning target volume (PTV) will be created using a 3-mm geometric margin for setup uncertainty. Radiotherapy will be delivered using photon-based image-guided IMRT, prescribed to a total dose of 40 Gy in 15 fractions, administered five days per week.

Experimental Arm Intervention: Patients in the experimental arm will undergo pretreatment evaluation, MRI-based simulation, and radiotherapy delivery similar to the standard arm, with the addition of pre-treatment F-DOPA PET imaging performed according to institutional consensus protocols. Biological target volumes (BTVs) will be delineated using a tumor-to-white-matter uptake ratio \>2.0. The initial clinical target volume (CTV-initial) will include the BTV, postoperative cavity, contrast-enhancing tumor on T1-weighted MRI, and gross disease. A 1.5-cm margin, edited for anatomical barriers, will generate the CTV-final to account for infiltrative spread. The planning target volume (PTV) will be created using a 3-5-mm geometric expansion. Dose prescription will be based on PTV volume and location. Patients with PTV \>30 cc or tumors not involving the brainstem will receive 40 Gy in 10 fractions to the BTV and 35 Gy in 10 fractions to the PTV. Those with PTV ≤30 cc or brainstem involvement will receive 30 Gy in 5 frac

Study summary

High grade gliomas, particularly glioblastoma, are among the most aggressive brain tumors and are associated with poor outcomes despite standard treatment. Many patients, especially older adults or those with poor general health, are not suitable for surgery and have a life expectancy of less than 12 months. Current standard includes a shortened course of radiotherapy (over 3 weeks) combined with chemotherapy using temozolomide (TMZ), which offers limited survival benefits. This study aims to explore whether delivering radiotherapy in a shorter duration (1 or 2 weeks) at a higher dose, guided by advanced imaging with a PET scan, can improve survival in this group of patients. PET scans help identify the most active parts of the tumor, which aids in targeting of these areas more precisely, potentially improving outcomes while reducing harm to healthy brain tissue. This study will randomly assign 116 eligible patients into two groups:

* One group will receive the current standard of care (3-week radiotherapy + TMZ).
* The other group will receive PET-guided radiotherapy over a shorter duration (either 5 or 10 sessions) at a higher dose, alongside TMZ.

The primary goal is to compare overall survival at one year between the two groups. The study will also assess how the disease progresses, side effects of treatment, and the impact on patients' quality of life. The study will be conducted over a total period of 6 years, including 4 years for patient enrolment and 2 years of follow-up. Participation in the study is entirely voluntary, and all patients will undergo an informed consent process. The study has been designed to follow all applicable ethical and regulatory guidelines. The results may help establish a more effective and convenient treatment option for patients with aggressive brain tumors and poor prognosis.

Eligibility

Primary outcome measure(s)

• Survival Outcomes — 1 year
  . Overall Survival will be defined as the time elapsed from the date of randomization to date of death due to any cause.

Trial sites (1)