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

Roman Kowalchuk, Trey C. Mullikin, William Breen, Hunter C. Gits, Marcus Florez, Brian De, William S. Harmsen, Peter Sean Rose, Brittany L. Siontis, Brian A. Costello, Jonathan M. Morris, John J. Lucido, Kenneth R. Olivier, Brad Stish, Nadia N. Laack, Sean Park, Dawn Owen, Amol J. Ghia, Paul D. Brown, Kenneth Wing Merrell

Research output: Contribution to journalArticlepeer-review


Background: Though metastasis-directed therapy (MDT) has the potential to improve overall survival (OS), appropriate patient selection remains challenging. We aimed to develop a model predictive of OS to refine patient selection for clinical trials and MDT. Patients and methods: We assembled a multi-institutional cohort of patients treated with MDT (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, number of additional non-target organ systems involved (NOS), and intracranial metastases. Results: A database of 1,362 patients was assembled with 424 intracranial, 352 lung, and 607 spinal treatments (n=1,383). 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), with lower scores indicating more favorable OS. The model demonstrated high concordance in the TC (0.72) and IVC (0.72). The score also demonstrated high concordance for each target site (spine, brain, and lung). Conclusion: This pre-treatment decision tool represents a unifying model for both intracranial and extracranial disease and identifies patients with the longest survival after MDT who may benefit most from aggressive local therapy. Carefully selected patients may benefit from MDT even in the presence of intracranial disease, and this model may help guide patient selection for MDT.

Original languageEnglish (US)
Article number1095170
JournalFrontiers in Oncology
StatePublished - 2023


  • metastasis-directed radiotherapy
  • metastatic disease
  • modeling
  • oligometastasis
  • outcomes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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