Improvement of Local Control in Skull Base, Spine and Sacral Chordomas Treated by Surgery and Protontherapy Targeting Hypoxic Cells Revealed by [18F]FAZA) PET/CT Tracers

Due to the close contacts of the lesion with the neurovascular structures, in the case of skull base chordoma and mobile spine, surgery is often incomplete. On the contrary, surgery of the sacral region (for which the block excision is often possible) brings a better therapeutic outcome. Radiotherapy with high-dose supplement improves the outcomes for all these lesions.

Intratumoral hypoxia is a primary factor of radioresistance, it's known since long by radiation oncologists. [18F]FAZA gives an image of the hypoxic volume target. Investigators propose to increase the radioactive dose in the hypoxic volume target but in order to succeed, radiation oncologists have to precisely identify this hypoxic volume. Radiation oncologists would increase of 10% the radioactive dose that will allow us to improve local control at 3 years of 15% without any additional side effect.

Inclusion criteria

• Typical chordoma and chondroid chordoma of the skull base, spine or chordoma of sacral region
• Patient undergoing an additional or exclusive radiotherapy (Photontherapy and/or Prothontherapy)
• Age ≥ 18 years old
• ECOG performance status 0 to 2
• Satisfying biological functions 28 days before inclusion :

• Haemoglobin ≥ 9 g/dL
• Neutrophils ≥ 1500/mm3
• Platelets ≥ 100 000/mm3
• ASAT, ALAT, GGT, PAL ≤ 1.5 N, bilirubin ≤ 40 μmol/L, LDH ≤ 1.5 N
• Creatininemia < 1.5 N
• Satisfying vital cardiac and respiratory functions
• Neurologic functions well stabilised
• Effective contraception for women of childbearing age during the the protontherapy treatment and during the month following the end of treatment. A pregnancy test shall be negative at inclusion.
• Patient covered by health insurance
• Patient provided with information and signature of informed consent.

Exclusion criteria

• Dedifferentiated chordomas, chondrosarcoma
• History of cancer (except cutaneous basocellular epithelioma or epithelioma of the uterine cervix) having recurred in the 5 years preceding entry in the trial and no relapse in the last 3 years
• Metastatic patient
• History of brain radiation therapy, or base of the skull or spinal segments to be treated
• Contraindications to radiotherapy
• Contraindications to PET/CT examinations [18F] Fluorodexoxyglucose (FDG) and [18]FAZA
• Associated pathology likely to prevent the patient from receiving treatment,
• Incompatible treatment with the inclusion in the study (oxygen therapy, EPO, anti-vascular treatments, anti-angiogenic treatments)
• Patient already included in another therapeutic trial with an experimental medication,
• Patient currently nursing,
• Persons deprived of their liberty, or under guardianship,
• Impossibility of undergoing the trial's medical follow-up for geographical, social or psychological reasons.