Safety and Efficacy of Dose-Escalated Radiotherapy with a Simultaneous Integrated Boost for the Treatment of Spinal Metastases

Abstract

<h3>Purpose/Objective(s)</h3> Dose-escalated radiotherapy (RT) using a spinal simultaneous integrated boost (SSIB) has been recently utilized for treatment of metastatic lesions not amenable to spine stereotactic radiosurgery (SSRS). Prior reports have utilized small sample sizes with short follow-up times. Our goal was to characterize the long-term efficacy and safety of this technique in a large cohort of patients with long term follow-up. <h3>Materials/Methods</h3> We reviewed 58 patients with 63 spinal metastatic sites that were treated with RT using a SSIB between 2012 and 2021. All patients received 30 Gy to the clinical tumor volume (CTV)and 40 Gy to the gross tumor volume, each delivered simultaneously in 10 fractions (GTV). Acute and late toxicities were noted for each patient. Local control (LC) was defined as having no progression on magnetic resonance imaging (MRI) at the SSIB-treated site. Overall survival (OS) was defined as the time from initiation of SSIB to death or last follow up, and was estimated using the Kaplan-Meier method. Multivariable Cox analysis was performed to identify associations with OS and LC. <h3>Results</h3> In our cohort, the median Karnofsky Performance Score (KPS) prior to RT was 80 (interquartile range [IQR], 80-90). Tumor histology was considered to be radioresistant in 81% of patients. Most patients had paraspinal involvement (65%) and epidural extension (82%). The median follow-up was 31 months with a median OS of 18 months (95% confidence interval [CI], 13-27 months). OS at 1, 2, and 3 years were 64%, 45%, and 24%, respectively. Actuarial LC was 98% (CI, 95-100%) and 95% (CI, 89-100%) at 1 and 2 years, respectively. The median GTV and CTV doses were 4123 cGy (range, 3400-4318 cGy) and 3641 cGy (range, 3302-4089 cGy), respectively. The mean cord dose was 2401 cGy (range 59-3168 cGy). The most commonly observed acute toxicities were fatigue (41%), pain (38%), esophagitis (8%), and nausea (8%). However, only one patient (2%) experienced Grade 3 or higher toxicity (pain). At last follow-up, no patients had developed myelopathy and all patients maintained ambulation. Following RT, pain improvement was achieved in 82% with a median pain score of 2 (IQR, 1-4) out of 10 from a pre-RT baseline of 4 (IQR, 3-6). Multivariable Cox analysis revealed that higher KPS score prior to RT (hazard ratio [HR], 0.40, 95%, CI, 0.20-0.84; <i>P</i>=0.016) was associated with longer OS, whereas increased size of PTV (HR 1.003, CI 1.001-1.005; <i>P</i>=0.017) was associated with shorter survival. <h3>Conclusion</h3> Our data show that the use of RT with SSIB provides favorable LC and OS with improved pain relief for selected patients that are not amenable for SSRS. Importantly, there were limited acute toxicities with no observed instances of radiation-induced myelopathy. Multi-institutional validation is warranted.