Background
Methods/design
Aims
Overview of the design
Participants
PREST trial eligibility criteria | |
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Inclusion criteria | Exclusion criteria |
• Patients diagnosed with spinal bone metastases from solid, uncomplicated tumor • Primary or secondary tumor histology related to the treatment lesion • Patients aged > 18 years • Obtained informed consent • ECOG 0–2 • Symptomatic patients at the treatment site (NRS ≥ 4) • Symptomatic patients at the treatment site (NRS 1–3) assuming opioid therapy ongoing for more than 3 days • Spine Instability Neoplastic Score (SINS) < 7 • Prognosis > 6 months according to Mizumoto Prognostic Score (i.e., classes A and B) • Spinal metastases verified at MRI, including the sites to be enrolled • No more than three non-contiguous spinal segments (e.g., separated by at least two metamers) involved in the study | • Unable to assign specific NRS for each CTV to be enrolled • Unable to express autonomous consent to therapies • Pregnancy • Patient in hospice or with prognosis < 6 months • Unavailability forecast for follow-up • Absence of MRI pre-treatment study • Unable to maintain the treatment position for SBRT • Previous radiotherapy at the same site or at the level of adjoining metameres (higher or lower than the one to be enrolled) • Previous radiometabolic therapy • Previous enrolment of the same patient for three irradiated lesions • Epidural compression of the spinal cord or of the cauda equina • Injuries affecting > 25% of the medullary canal and/or a distance < 5 mm from the medulla or from the cauda • Injuries with indication of surgical stabilization • Chemotherapy or target therapy within the previous 7 days and 7 days after SBRT |
Registration
Randomization
Radiotherapy
Follow-up
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0: no pain (better outcome)
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1–3: mild pain
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4–6: moderate pain
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7–10 severe pain (worse outcome)
Toxicity management
Discussion
Outcomes
Endpoint definitions and measurement | |
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Primary outcome measure | |
Pain control (efficacy and pain; time frame 3 months) Overall pain control measured according to IBMC (complete response + partial response events) | |
Secondary outcomes measures | |
• Pain control duration (efficacy and pain; time frame 12 months after end of radiotherapy) Interval from the end of the RT to relapse of the symptom • Rate of retreatments (efficacy; time frame 12 months after end of radiotherapy) Interval from the end of the RT to the start of retreatment • Local control (efficacy; time frame 3, 6, and 12 months from the end of radiotherapy) Control of local disease with diagnostic exams according to RECIST 1.1 criteria • Symptom progression-free survival (SPFS) (efficacy and pain); time frame 12 months after end of radiotherapy) Interval from the end of radiotherapy and progressive disease with symptoms according to the criteria of Chow et al. in 2012 [8] • Progression-free survival (efficacy; time frame 12 months) Interval from the end of radiotherapy and new disease progression • Overall survival (efficacy; time frame 12 months) Interval between the end of radiotherapy and death • Quality of life (efficacy and quality of life; time frame first visit, 1 month, and 3 months after the end of radiotherapy) Quality of life score according to European Organization for Research and Treatment of Cancer (EORTC) QLQ-C15-PAL and QLQ– BM22 questionnaires |
Statistical considerations and sample size
Ethics considerations
Quality assurance
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Diagnostic imaging: MRI imaging before treatment for GTV contouring; follow-up MRI imaging at 3 months is recommended but not mandatory
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Personalized set-up system: the use of personalized set-up systems is considered mandatory
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Planning verification: every single treatment plan needs to respect coverage and constraints indicated in the protocol; before enrolling, every single center should participate in dummy studies to confirm its treatment planning possibilities
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Image-guided radiotherapy (IGRT): Cone-beam daily acquisition before treatment is mandatory to assure good IGRT. A six-degree-of-freedom couch is recommended but not mandatory for set-up error correction