Overview

Glioblastoma (GBM) is the most common primary brain cancer in adults. Surgery, chemoradiotherapy (temozolomide TMZ) and then adjuvant TMZ is the standard treatment. But, most patients relapse in a median time of 8-9 months; the median overall survival (OS) ranged from 15 to 18 months.

Some frail patients received hypofractionated radiation and concomitant and adjuvant TMZ. For some, the radiation dose is not optimal. Moreover, recurrences develop mainly in the initial tumor site. These two reasons justify increasing the dose. To limit the movements of these fragile patients, the method consists of increasing the dose without increasing the number of sessions by using the Simultaneous Integrated Boost (SIB) which increases the dose in targeted volumes while the rest of the volume receives a minimum dose. A phase I trial showed the possibility of increasing the dose in SIB up to 80 Gy in a part of the GBM enhanced on MRI.

FDOPA PET detects certain more aggressive tumor areas, areas likely to recur. Integrating them into the SIB seems appropriate. A phase II trial showed the interest of SIB guided by FDOPA PET in terms of progression-free survival but without impact on OS. This study differed from the one the investigators propose, because a dose and conventional fractionation, identical to that of the European Organization for Research and Treatment of Cancer/National Cancer Information Center (NCIC/EORTC) protocol were delivered, the gliomas were unmethylated MGMT, less likely to respond. Studies with SIB and hypofractionation are often retrospective and for others, hypofractionation was debatable and the dose increase was not based on PET capture but on MRI. However, a prospective phase II study, with SIB and hypofractionation, not integrating FDopa PET has demonstrated the relevance of SIB.

In this project, the investigators propose to use the integrated boost technique (SIB) guided by PET FDOPA to increase the radiation dose in GBM, in patients either fragile and partially operated, or only biopsied and for whom the prognosis is the most pejorative.

Eligibility

Inclusion Criteria:

• Unfit patient without indication to the STUPP protocol :

Cohort 1 : Non-operable patients and ≥ 18 years old or ≤ 70 years old and Karnofsky Index (KI) ≥ 50% on inclusion AND Result of a biopsy available Cohort 2 : Patients \> 70 years old and Balducci score I or II and KI ≥ 60% on inclusion AND Partial resection (defined on the remnographic criteria of postoperative MRI) OR biopsy result available

• Histologically proven glioblastoma
• Increased metabolism of amino acids in PET FDOPA allowing contouring the Biological Target Volume (BTV)

Exclusion Criteria:

• Patients with an indication for irradiation according to the STUPP protocol (fit patient)
• Patient with a contraindication to MRI or PET
• Limit of the provisional target volume or Planning target volume (PTV), second PTV \< 2 cm from the chiasm and the optic nerves
• Absence of uptake of FDopa