1264MO Development and validation of a unifying pre-treatment decision tool for intracranial and extracranial metastasis-directed radiotherapy

Metastasis-directed therapy (MDT) has the potential to improve clinical outcomes and even overall survival (OS). However, prognostication and appropriate patient selection for MDT remain challenging. We aimed to develop a unifying model predictive of OS for patients with intracranial and extracranial disease to refine patient selection for MDT and clinical trials. We assembled a multi-institutional cohort of patients treated with MDT to spine, brain, and/or lung metastases. Treatments included stereotactic body radiation therapy, radiosurgery, and whole brain radiation therapy. Candidate variables for recursive partitioning analysis were selected per prior studies: ECOG performance status, time from primary diagnosis (TPD), number of additional non-target organ systems involved (NOS), and intracranial metastases. A database of 1,362 patients was assembled with 424 intracranial, 352 lung, and 607 spinal treatments (n=1,383). Of patients treated for intracranial disease, 75% also had extracranial disease. Treatments were split into training (TC) (70%, n=968) and internal validation (IVC) (30%, n=415) cohorts. The TC had median ECOG of 0 (interquartile range [IQR]: 0-1), NOS of 1 (IQR: 0-1), and OS of 18 months (IQR: 7-35). The resulting model components and weights were: ECOG = 0, 1, and > 1 (0, 1, and 2); 0, 1, and > 1 NOS (0, 1, and 2); and intracranial target (2). The model demonstrated high concordance in the TC (0.72) and IVC (0.72). The score demonstrated concordance of 0.65-0.71 for each target site (spine, brain, and lung), and each variable used in the model met statistical significance (p<0.0001). This pre-treatment decision tool identifies patients with the longest survival after MDT, indicating a patient population with systemic disease who may benefit most from aggressive local therapy. This model represents a unifying model applicable in settings of both intracranial and extracranial disease. Carefully selected patients may benefit from MDT even in the presence of intracranial disease.