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Bone modifying agents and multikinase inhibitors as treatments for chordoma: A TriNetX-based retrospective cohort study
Journal article   Peer reviewed

Bone modifying agents and multikinase inhibitors as treatments for chordoma: A TriNetX-based retrospective cohort study

Kamal Shaik, Spencer Rasmussen, Rudy Rahme and Michael Karsy
Clinical neurology and neurosurgery, v 261, 109282
01 Feb 2026
DOI: https://doi.org/10.1016/j.clineuro.2025.109282
PMID: 41349423

Abstract

Bone-modifying agents Chordoma Multikinase inhibitors TriNetX
Chordomas are rare malignant tumors arising from embryonic remnants of the notochord, most commonly affecting the axial skeleton. Although advances have been made in surgical resection and radiation therapy, systemic treatment options remain limited. Bone-modifying agents (BMAs), including zoledronic acid and denosumab, as well as multikinase inhibitors (MKIs) like lenvatinib and cabozantinib, have emerged as potential targeted therapies based on preclinical models. However, comparative real-world data evaluating their outcomes in chordoma patients is lacking. A retrospective cohort study was conducted using the TriNetX Research Network. Patients with chordoma (ICD-10-CM C41.0, C41.2, C41.4) were stratified into treatment groups based on receipt of zoledronic acid, denosumab, or multikinase inhibitors (MKIs). Propensity score matching was used to adjust for baseline confounders. Outcomes evaluated at 5 years post-diagnosis included all-cause mortality, pathologic fracture, spinal cord compression, and osteonecrosis. Risk ratios with 95 % confidence intervals were calculated. Compared to denosumab, zoledronic acid was associated with a higher 5-year mortality risk, but a lower osteonecrosis risk. Comparisons involving MKIs showed no difference in mortality. No pathologic fractures were reported across cohorts. Spinal cord compression was not different among treatments. This study highlights potential differences in survival and skeletal-related outcomes among chordoma patients treated with BMAs, specifically denosumab and MKIs. These preliminary findings underscore the need for prospective studies to better define optimal systemic therapies for this rare malignancy. •Denosumab was associated with lower 5-year mortality than zoledronic acid.•Denosumab showed higher osteonecrosis risk compared with zoledronic acid.•MKIs and zoledronic acid demonstrated no mortality differences.•Spinal cord compression rates did not differ across treatment groups.

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Collaboration types
Domestic collaboration
Web of Science research areas
Clinical Neurology
Surgery
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