Plasma Cell-free DNA Levels as a Biomarker for Systemic Disease Burden in Metastatic Spine Disease

Introduction: Several prognostic scores exist to assist clinical decision making, but their performance is variable. This study aimed to assess the reliability of plasma cell-free DNA (cfDNA) levels as a biomarker for systemic disease burden in patients with metastatic spine disease.

Methods: This prospective study reports preliminary results of patients who underwent surgery and stereotactic radiosurgery for spinal metastases between June 2023-June 2024. Demographic, clinical, oncologic, and outcome variables were collected for each patient. Plasma cfDNA levels were assessed using kits made by DiaCarta, Inc. (Pleasanton, CA) preoperatively, postoperatively, pre-radiation therapy (RT), post-RT, and 6-weeks post-RT. cfDNA levels at each time point were analyzed for correlation with validated metastatic spine disease prognostic scores (Spinal Instability Neoplastic score, SINS; Modified Bauer score; New England Spine Metastatic score, NESMS; Revised Tokuhashi score; and SORG nomogram), postoperative Karnofsky Performance Status (KPS), and last follow-up survival via linear or logistic regression where appropriate.

Results: 31 patients received pre- and postoperative cfDNA draws, 14 received pre- and post-RT draws, and 7 received 6-week post-RT draws. Included patients were an average of 69.6 (±8.0) years old and primarily male (19/31). Lung (7/31) and renal (6/31) were the most common primary cancers and mean follow up was 5.84 (±4.9) months. Preoperative cfDNA levels correlated with NESMS scores (p=0.020), postoperative KPS (p=0.016), and survival (p=0.041). Postoperative cfDNA levels correlated with NESMS scores (p=0.021) and postoperative KPS (p=0.021). Pre-RT draws correlated with postoperative KPS (p=0.044), while 6-week post-RT cfDNA levels correlated with Modified Bauer (p=0.046), NESMS (p=0.032) and SORG nomogram (p=0.043) scores. Post-RT levels did not correlate with any outcome.

Conclusion : Plasma cfDNA levels correlate with validated prognostic scores and oncologic outcomes among patients with metastatic spine disease and may be a reliable biomarker for systemic disease burden. Future studies with larger samples and longer-term follow-up are ongoing to confirm these results.