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Improved local control of chordoma initially treated with surgery or not, thanks to adjuvant radiotherapy oriented by conventional imaging Computed Tomography /Magnetic Resonance Imaging (CT / MRI) and guided by the [18Fluor] ([18F]) Fluoroazomycin Arabinofuranoside (FAZA) Positron Emission Tomography / Computed Tomography (PET / CT) to target the radioresistant hypoxic cells.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| [18F]FAZA PET/CT | Experimental | In residual chordoma tumors after surgery, Investigators propose a protontherapy guided by conventional imaging (CT/MRI) and a boost guided by FAZA PET/CT, in order to target the hypoxic zones and to increase the dose in an adequate manner, which could result in improving long-term local control and reducing complications. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Surgery | Procedure | The operative approach and operating time will be performed according to neurosurgical practices (for head and neck) or surgical orthopaedic team (for sacrum) depending on the location, the extension and the relationship of the lesion to critical structures. The surgery can be macroscopically complete or incomplete. |
| Measure | Description | Time Frame |
|---|---|---|
| Improvement local control of chordomas according to RECIST criteria. | Rate of local control at 3 years | 36 months |
| Improvement local control of chordomas according to PERCIST criteria | Rate of local control at 3 years | 36 months |
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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 :
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:
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| Name | Affiliation | Role |
|---|---|---|
| Hamid MAMMAR, MD | Institut Curie | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Institut Curie - Hôpital René Huguenin | Saint-Cloud | Île-de-France Region | 92210 | France |
Investigators will share de-identified data sets with interested researchers, educators or clinicians. Materials generated under the project will be disseminated in accordance with Institut Curie policies.
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Data requests can be submitted starting 9 months after article publication and will be made accessible for up to 12 months.
Access to trial individual participant data can be requested by qualified researchers engaging in independent scientific reserach, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a data sharing agreement (DSA).
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| Protontherapy | Radiation | Radiotherapy will be done with the Cyclotron, for a total dose of 78 Gray Relative Biological Effective (Gy RBE) - 70 Gy RBE to the tumor bed and macroscopic volume and 8 Gy RBE to the the hypoxic component volume, delivered in 39 fractions spread over 67 days. |
|
| 18F FAZA | Drug | FAZA PET/CT, in order to target the hypoxic zones |
|
|
| ID | Term |
|---|---|
| D013514 | Surgical Procedures, Operative |
| C498052 | fluoroazomycin arabinoside |
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