Sacral Chordoma: Surgery Versus Definitive Radiation Therapy in Primary Localized Disease

Title of Study: SAcral Chordoma: a Randomized & Observational Study on Surgery Versus Definitive Radiation Therapy in Primary Localized Disease (SACRO)

Comparative study on surgery versus definitive radiation therapy in primary localized sacral chordoma

International, multicenter, comparative, open-label, parallel-group, mixed Observational-Randomized Controlled Trial.

All the patients, who are candidate for the study will receive full information on the characteristics, potential effectiveness and side effects of the two alternatives treatments: radiotherapy (RT) and surgical treatment Eligible patients will be asked to be randomized in order to receive treatment A (surgery, with or without RT) or treatment B (definitive RT) Who will refuse randomization will be included in the Prospective Cohort Study (PCS) and will be treated accordingly to their choice (treatment option A or treatment option B).

The same radiotherapy and surgical regimen will be administered in the PCS and in the Randomized Clinical Trial (RCT) cohort

Inclusion Criteria:

• Histologically confirmed diagnosis (brachyury expression) of primary sacral chordoma,of any diameter and arising at any site from S1 to coccyx.
• Age≥18years
• ECOG-performance status (PS) 0-2
• No previous antineoplastic therapy
• Macroscopic tumor detectable at MRI/CT scan
• Patient amenable for surgery
• Patient amenable for RT
• Written informed consent given before the enrolment, according to International Conference on Harmonisation/good clinical practice (ICH/GCP).

Exclusion Criteria:

• Distant metastasis
• Inability to maintain treatment position
• Prior radiotherapy to the pelvic region
• Prior therapy for sacral chordoma (including surgery, cryoablation, hyperthermia, etc)
• Local conditions that increase the risk of RT toxicity (tumor ulcerated skin infiltration, non-healing soft tissue infection, fistula in treatment field)
• Rectal wall infiltration
• General conditions that increase the risk of RT toxicity (active sclerodermia, xeroderma pigmentosum, cutaneous porphyria)
• Presence of a second active cancer (with the exception of non-melanoma skin cancer in-situ cervix neoplasia and other in-situ neoplasia)
• Severe comorbidities resulting in a prognosis of less than 6 months
• Inability to give informed consent
• Other malignancy within the last 5 years
• Performance status ≥ 2 (ECOG).
• Significant cardiovascular disease (for example, dyspnea > 2 NYHA)
• Significant systemic diseases grade >3 on the NCI-CTCAE v4.03 scale, that limit patient availability, or according to investigator judgment may contribute significantly to treatment toxicity
• Women who are pregnant or breast-feeding
• Psychological, familial, social or geographic circumstances that limit the patient's ability to comply with the protocol or informed consent