Multi-Institutional Validation of the Recursive Partitioning Analysis for Overall Survival in Patients Undergoing Spine Radiosurgery for Spine Metastasis

Abstract

The recently published spine radiosurgery (sSRS) recursive partitioning analysis (RPA) for overall survival (OS) separated patients into 3 distinct prognostic groups. We sought to externally validate this RPA using 3 separate multi-institutional datasets. A total of 444 patients were utilized to develop the recently published sSRS RPA predictive of OS in patients with spine metastases. The RPA identified three distinct prognostic classes. RPA Class 1 was defined as KPS >70 and controlled systemic disease (n = 142); RPA Class 2 was defined as KPS>70 with uncontrolled systemic disease or KPS ≤70, age ≥54 and absence of visceral metastases (n = 207); RPA Class 3 was defined as KPS ≤70 and age <54 years or KPS≤70, age ≥54 years and presence of visceral metastases (n = 95). We utilized data from 3 large tertiary care centers to independently validate this RPA. Data from each institution was utilized independently to validate the RPA to minimize confounding based on institutional differences in patient selection. A total of 1,184 patients (221 patients from institution A, 749 institution B, and 214 from institution C) were in the validation cohort and were divided based on their RPA Class. Kaplan-Meier method was used to estimate OS and log-rank test was used to compare OS between RPA classes. In each of the validation cohorts, the median OS was 19.9 months (institution A), 11.0 months (institution B), and 24.4 months (institution C). The patient distribution into RPA classification based on Institution A/B/C was, Class 1 (19.4%, 15.1%, 50.5%), Class 2 (74.7%, 57.7%%, 37.9%), and Class 3 (5.9%, 27.2%%, 11.2%), respectively. The median OS for patients in the validation cohort at Institution A/B/C based on RPA class was Class 1 (54 months, 27.1 months, 50.0 months), Class 2 (15.9 months, 13.0 months, 15.1 months) and Class 3 (6.9 months, 3.5 months, 6.1 months), respectively. Patients in RPA Class 1 had a significantly better OS compared to those in Class 2 of the each of the three external institution validation cohorts (p<0.01). Similarly, patients in RPA Class 2 had a significantly better OS compared to those in Class 3 (p<0.01). The external datasets from three large institutions independently validated the spine SRS RPA successfully for OS in patients undergoing sSRS for spinal metastases. This is the first RPA for OS to have been externally validated using multiple large datasets. Based on this validation, upfront spine SRS is strongly supported for patients in RPA Class 1 and Class 2 and is also cost effective with median OS >11 months for these patients. Patients in RPA Class 3 would benefit most from upfront conventional radiotherapy given their poor expected survival. Given successful external validation, this RPA helps guide physicians to identify those patients with spinal metastases who most benefit from sSRS.