Imaging-Based Local Control Rates For “Radioresistant” Spinal Metastases Following Spine Stereotactic Body Radiotherapy Using Prostate Cancer As The “Radiosensitive” Reference

Abstract

It is thought that stereotactic body radiotherapy (SBRT) challenges the notion of a radioresistant phenotype given the high rates of local control. To determine the impact on local control for those classically considered radioresistant spinal metastases, we compared outcomes following spine SBRT using prostate cancer metastases as the radiosensitive comparator. We retrospectively reviewed a prospectively maintained database of 1394 spinal segments in 605 patients treated with SBRT between January 2009 to December 2018, and identified renal cell carcinoma (RCC), melanoma, sarcoma, colon cancer, and thyroid cancer metastases as the radioresistant cohort and prostate cancer metastases as the radiosensitive cohort. All patients were serially followed with clinic visit and full spine MRI every 2 to 3 months. The primary endpoint was imaging-based local control using the prostate cancer cohort as the comparator, and secondary endpoints included overall survival (OS) and vertebral compression fracture (VCF). 173 patients/395 radioresistant spinal segments were compared to 94 patients/185 prostate cancer spinal segments and median follow-up was 15.5 months (range: 1.4-84.2 months). For the entire cohort, the majority had an ECOG of 0-1 (87.3%), were treated with 24-28 Gy in 2 fractions (71.9%), and half had oligometastatic disease (53.9%). 1- and 2-year local control (LC) rates for the radioresistant cohort were 80.8% and 77.6%, as compared to 96.8% and 91.6% for the prostate cancer cohort. Variation amongst radioresistant histologies was observed with 1-year LC rates of 76.2% for melanoma (41/395), 76.3% for colon cancer (85/395), 81.1% for renal cell carcinoma (225/395), 86.2% for thyroid cancer (29/395), and 100% for sarcoma (15/395). Local failure was associated with presence of epidural disease (HR 2.481, 95% CI: 1.652-3.724, p<0.0001), radioresistant histology (HR 2.318, 95% CI: 1.397-3.848, p = 0.0011), and a lower CTV V90 (p<0.0001). For the radioresistant and prostate cancer cohorts the median OS was 17.4 and 61.0 months and the 2-year OS rates were 37.4% and 81.4%, respectively. Presence of lung, liver and brain metastases, widespread (non-oligometastatic) disease, epidural disease and ECOG ≥ 2 were prognostic for worse OS. Non-significant differences in the 1- and 2-year VCF rates at 9.8% and 14.1%, and 5.1% and 12.7%, were observed in the radioresistant and prostate cancer cohorts, respectively. Coverage of CTV V95 by > 0.87 (HR 2.32, 95% CI: 1.29-4.18, p = 0.005), no-prior radiotherapy at index lesion (HR 1.963, 95% CI: 1.086-3.546, p = 0.0254), and higher SINS score (p = 0.0125) predicted for VCF. Our results confirm a significant difference in local control rates amongst those histologies classically considered radioresistant compared to radiosensitive. Although local control rates are still high, optimization strategies may include dose escalation and more aggressive management of epidural disease.