PREST: Pain REduction with bone metastases STereotactic radiotherapy: A phase III randomized multicentric trial

Abstract Background Palliative antalgic treatments represent an issue for clinical management and a challenge for scientific research. Radiotherapy (RT) plays a central role. Techniques such as stereotactic body radiotherapy (SBRT) were largely investigated in several phase 2 studies with good symptom response, becoming widely adopted. Still is lacking evidence from randomized, direct comparison of RT and SBRT. Methods/Design The PREST trial was designed as an interventional study without medicinal, randomized 1:1, open-label, multicentric, phase 3. Inclusion criteria: painful spinal bone metastases presenting pain level >4 (or >1 if assuming analgesic) at numeric rating scale (NRS); expected intermediate/high prognosis (superior to 6 months) according to the Mizumoto prognostic score; low spine instability neoplastic score (SINS) sores (<7); magnetic resonance imaging (MRI) assessment of the bulky lesion. Patients will be assigned to either standard conventional radiotherapy administering 4 Gy x5 fractions (fx) to whole involved vertebra or SBRT by intensity modulated radiotherapy with simultaneous integrated boost (IMRT-SIB) administering 7 Gy x3 fx (to the whole involved vertebra) + 10 Gy x3 fx on the macroscopic disease (Gross Tumor Volume -GTV). In the experimental arm, the GTV will be contoured by registration with baseline MRI. Discussion Primary endpoint is overall pain reduction, defined in term of variation between baseline and 3-month evaluation; pain will be measured by Numeric Rating Scale (NRS) score. Secondary endpoints include: pain control duration; retreatment rates (after a minimum interval of 1 month); local control assessed with RECIST Criteria; symptom progression free survival; progression free survival; overall survival and quality of life (at 0, 30 and 90 days). Accrual of 330 lesions is planned. Experimental arm is expected to improve overall pain response rates of 15% respect to standard arm (60% according to Chow et al 2012).