Contribution From PET-DOPA in Glioblastoma Re-irradiation - A Randomized Phase II Study

Glioblastoma (GBM) is the most common cerebral tumor in adults. Despite well-conducted treatments including surgery, chemo-radiotherapy and chemotherapy according to the European Organisation for Research and Treatment of Cancer (EORTC) and National Cancer Institute of Canada Clinical Trials Group (NCIC) protocol, recurrences remain unavoidable within approximately 6 months and the overall survival rate of patients at 5 years is inferior to 10%.

In case of recurrence, a second surgery, radiotherapy under stereotaxic conditions, bevacizumab or other innovative techniques have been proposed. However, they are not yet considered as reference treatments, due to the absence of therapeutic trials definitively proving their efficacy.

Evaluation of GBM progression is based on MRI, corticosteroid intake and clinical status.However, positron emission tomography (PET) is an extremely relevant examination for differentiating between true progression and pseudo-progression. Indeed, an increase in the transfer of amino acids in 18 F-dihydroxyphenylalanine (FDOPA)-PET strongly suggests a recurrence. A local treatment can then be proposed by favoring surgery or, as an option, radiotherapy under stereotactic conditions. However, this treatment, even if it is well tolerated, has an efficacy which could be improved.

Often proposed option to improve efficacy of this radiation technic consists in increasing the dose of irradiation. This dose increase is often limited by the tolerance of nearby healthy tissue. It could however be possible with coupled techniques of intensity modulation and stereotaxy within the framework of an integrated boost (Simultaneous Integrated Boost - SIB). At each radiation session, the dose delivered to the tumor volume would be increased in the metabolic volume (BTV) detected by FDOPA-PET.

The objective of this study is to evaluate, in patients with recurrent glioblastoma, the efficacy of a dose increase using an SIB in a volume delineated with FDOPA-PET.

• Percentage of recurrence of irradiated sites [Time frame: up to 24 months]
• Characterization of recurrence sites: classified either as distant, marginal or in-field [Time frame: up to 24 months]
• Percentage of Recurrence free survival at 6 months [Time frame: At 6 months]
• Percentage of Recurrence free survival at 12 months [Time frame: at 12 months]
• Overall survival [Time frame: From date of inclusion until the date of death from any cause, assessed up to 72 months]
• Tolerance of re-irradiation [Time frame: up to 24 months]
• Characterization of PET parameters at recurrence and compare them to baseline parameters with SUV max value [Time frame: up to 24 months]
• Characterization of PET parameters at recurrence and compare them to baseline parameters with SUV mean value [Time frame: up to 24 months]
• Characterization of PET parameters at recurrence and compare them to baseline parameters with SUV peak value [Time frame: up to 24 months]
• Quality of Life at 2 months measured with Quality of Life Questionnaire-Cancer 30items (QLQ-C30) [Time frame: At 2 months]
• Quality of Life at 2 months measured with Quality of Life Questionnaire-Brain Neoplasms 20items (QLQ-BN20) [Time frame: At 2 months]
• Quality of Life at 4 months measured with Quality of Life Questionnaire-Cancer 30items (QLQ-C30) [Time frame: At 4 months]