FET-PET Directed Simultaneous In-field Boost for Primary GBM

Study Overview
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Brief Summary
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The combination of anatomical MRI examination with functional examination of tissue metabolic activity such as FET-PET (PET using the radiotracer - 18F-fluoro-ethyl-tyrosine) is a valuable tool to determine the actual tumor infiltration. The FET-PET examination can be performed using the dual-time point aqusition of FET for exact treatment planning. It has also been proven that using the dual FET-PET method, it is possible to obtain a precise image of the glioblastoma infiltration corresponding to the location and shape of the recurrence, and the tumor volumes in dual FET-PET are significantly larger than in MRI. Moreover, tumor defined in dual FET-PET is different than that of the tumor defined in single FET-PET acquisition. In the DualFETboosT trial we plan to assess the safety and preliminary efficacy of hypofractionated irraditon using simultaneous in-field boost directed on dual FET-PET based tumor volumes for treatment of primary glioblastoma multiforme with concomitant temozolomide.

Detailed Description
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In the case of the treatment of glioblastoma multiforme, as a standard, radiotherapy lasts 6 weeks, and the extension of treatment may adversely affect the tumor cells death, the patient's well-being and treatment costs (prolonged hospitalization). In turn, escalating the dose may increase the toxicity of radiation therapy by increasing DNA damage in healthy brain tissue. Using of dual FET-PET images for treatment planning allow to reduce volumes of healthy tissue irradiated. Dose-intensification proposed in the study using simultaneous in-field boost allows the dose escalation without increasing the overall treatment time. All patient will be treated with moderately hypofractionated radiotherapy (2.6 Gy per fraction) directed on PET positive volumes and conventional fractionation (60Gy in 30 fractions) on tumor margin.

Official Title
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Safety and Preliminary Efficacy of Hipofractionated Irradiation Based on Dual FET-PET in Patients With Primary Glioblastoma Multiforme With Concomitant Temozolomide

Conditions
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Glioblastoma Multiforme

Intervention / Treatment
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* Radiation: Moderately Hypofractionated Radiotherapy using Simultaneous In-Field Boost


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histopathological confirmation of glioblastoma (WHO grade IV) Age between 18-75 years of age General condition according to the Zubrod scale 0 or 2 The results of the blood counts are normal Liver enzyme parameters normal The results of the parameters of the patient's functions are normal Informed consent to participate in the category Exclusion Criteria: Coexistence of another cancer The location of the tumor in the area of the brain stem or cerebellum Prior brain radiation therapy No uptake visible in the FET-PET imaging Contraindications for MRI Contraindications to radiotherapy or chemotherapy Pregnancy, lack of consent to the use of protection against pregnancy, puerperium Alcohol addiction Mental illness Claustrophobia

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Simultaneous In-Field Boost on FET-PET positive target volumes<br> | Radiation: Moderately Hypofractionated Radiotherapy using Simultaneous In-Field Boost<br>* 78Gy in 30 fractions on FET-PET based target volumes; 60Gy in 30 fractions on 2cm margin from MRI based target volumes; all patients will be treated with concomitant and adjuvant temozolomide<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | From date of surgery until the date of death from any cause, percent of patient that are alive 1 and 2 years after surgery | assessed up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival | from the date of surgery until progression of the disease or the date of death from any cause assessed | up to 24 months | 
| Objective response | according to Rano criteria; from the end of radiation therapy | up to 9 months | 
| Location of treatment failure | from the end of radiation therapy up to progression until progression of the disease or the date of death from any cause; according to irradiation field | up to 24 months | 
| Radiation necrosis | from the end of radiation therapy up to progression until progression of the disease or the date of death from any cause; histopathological diagnosis of radiation necrosis | assessed up to 24 months | 
| Side effects | from the end of radiation therapy up to progression until progression of the disease or the date of death from any cause; CTCAE grade 3 or higher | up to 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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FET-PET, Boost, Glioblastoma, Dose-intesification, Dose-escalation