Comparison of Multi-Fraction Versus Single-Fraction Stereotactic Body Radiation Therapy (SBRT) for Symptomatic Bone Metastasis: Results of the STAT RT and STAT RAD Phase I/II Prospective Trials

Purpose/Objective(s): To compare the outcomes of multi-fraction versus single-fraction dose escalated radiation therapy for bone metastases using a Scan-Plan-QA-Treat patient centric workflow. Materials/Methods: Two prospective, phase I/II, IRB approved clinical trials were performed to assess the effectiveness of expedited multi-fraction (STAT RT) and single-fraction (STAT RAD) SBRT for painful bone metastasis. Eligible patients for both trials had 1-3 painful axial or extra axial bone metastases, which had not been previously irradiated. Subjects in STAT RT underwent a treatment course of 2-5 fractions at 5-10 Gy per fraction. Following the completion of STAT RT, STAT RAD enrolled patients onto a dose escalation trial, to receive 8-15 Gy in one fraction. Both trials utilized a Scan-Plan-QA-Treat workflow, allowing for same day CT simulation and treatment with helical 3D conformal radiation therapy. Chi-squared test was used to compare proportions. Results: 28 patients were enrolled and 37 bone metastases (76% axial) were treated in the multi-fraction trial. In the single-fraction trial, 46 patients were enrolled and 60 bone metastases (55% axial) were treated. Median time between consultation and initiation of treatment was 4 days in the multi-fraction trial and 2 days in the single-fraction trial. 96% (n=27) of patients in the multi-fraction trial and 93% (n=43) of patients in the single-fraction trial underwent CT simulation and treatment on the same day. In STAT RT, patients were treated to a median BED10 of 37.5Gy (range 14.4 - 72); however, 24Gy in 3 fractions was the most commonly prescribed regimen. For STAT RAD, patients were treated to a median BED10 of 28.1Gy (range 14.4 - 37.5); 12.5Gy in 1 fraction was most commonly prescribed. The re-treatment rate was 5.4% (2/37) in the multi-fraction study and 16.7% (10/60) in the single-fraction study (p = 0.10). The median time to re-treatment was 10.4 months vs 5.7 months in the multi-fraction and single-fraction trials, respectively. In both trials, two patients recurred at the field edge of a treated lesion and were treated with radiation to the site of recurrence. There were 11 adverse events reported in STAT RT (all ≤ G2) and 10 reported on STAT RAD (2 G3, all others G1). There was a G1 fracture in the multi-fraction trial and a G3 fracture in the single-fraction trial, in the setting of trauma and disease progression, respectively. Conclusion: Dose escalated radiation therapy can be safely planned and delivered in the same day via our Scan-Plan-QA-Treat workflow. We found no significant difference in re-treatment rates between the single versus multi-fraction trials. However, a trend towards a decreased rate of re-treatment and an increased interval to re-treatment argues for a multi-fraction, higher radiobiologic dose for patients with potential for durable control of their systemic disease.