THE IMPACT OF TARGETED THERAPY ON SURVIVAL AFTER SPINE METASTASIS: A SYSTEMATIC REVIEW AND POOLED DATA ANALYSIS

Tumor specific targeted immunotherapy has substantially impacted the quality and quantity of life for patients with spinal metastatic malignancies. Numerous scoring utilities such as the Tokuhashi, Tomita or Spinal Instability Neoplastic score (SINS) are often used to prognosticate treatment and guide surgical management. However, many of these scoring systems are potentially outdated and do not reflect the recent advances made in medical oncology and targeted therapeutic treatment. The primary aim of this research was to investigate the current state of the literature and treatment options pertaining to advancements in targeted systemic therapy compared to other forms of medical management for metastatic spinal tumors. A systematic literature review and pooled data analysis were performed to evaluate the median overall survival (mOS) for patients with metastatic spinal tumors originating from five (lung, breast, renal, melanoma, thyroid) common primary cancers. A comprehensive search of PubMed was conducted by two authors to identify relevant articles for review. Following PRISMA guidelines, 28 of 1834 initially identified articles met our inclusion criteria, encompassing the five primary tumor locations. Lung cancer articles (n=16) reported a weighted mOS of 6.8 months, while articles on breast cancer (n=5) showed 24.0 months, renal cancer (n=3) demonstrated 58.1 months, and thyroid cancer (n=1) exhibited 123.0 months. 15/16 identified articles on lung cancer with spinal metastases included targeted therapy (TT), primarily utilizing EGFR-TKI, resulting in significant improvements in mOS (21.0 months) compared to those without TT (5.65 months). Six of these articles reported statistically significant (p < 0 .05) hazard ratios (HR), and the pooled HR was found to be 0.486. Breast cancer patients who received TT also had a higher overall mOS (83.2 months) compared to those without TT (overall mOS = 32.86). All three melanoma papers reported patients receiving TT, with two showing a mOS improvement, and notably, one paper indicated significance thereof (HR: 0.32, CI: 0.17-0.58, p=0.0002). Of all included articles, only five studies utilized bisphosphonate therapy. Among these, four demonstrated an extension in mOS when compared to non-treatment groups, with three of them showing statistically significant improvements (p < 0 .05). Among the five lung cancer papers that reported outcomes for both chemotherapy and non-chemotherapy groups, four indicated higher mOS with chemotherapy, with one showing statistical significance (p < 0 .001). Similarly, the breast cancer paper reporting chemotherapy outcomes demonstrated a significant mOS improvement (p=0.013). Articles were excluded if they did not consistently report chemotherapy use or provide survival outcomes. Based on this review and pooled data analysis, targeted therapy, especially in lung and breast cancers, demonstrated the most notable improvements in mOS. Our study provides valuable insights into the recent advancement of medical management of metastatic spinal tumors. Future indications include incorporating this literature into personalized treatment approaches to metastatic spine tumors.