The Genomic Analysis of Patients with Musculoskeletal Metastases from an Unknown Origin.

Eastley, Nicholas; Cool, Paul; Jafri, Mariam; Raghavan, Manoj; Stevenson, Jonathan

Abstract

Background
A subgroup of patients present with musculoskeletal (MSK) metastases but no detectable primary tumour. An inability to employ disease-specific treatment means this cohort's median survival is just 6–10 months. We present a novel, prospective, pilot study investigating the role of targeted Next Generation Sequencing (NGS) of metastases in these ‘Cancer of Unknown Primary’ (CUP) patients, reporting on diagnostic, therapeutic and prognostic benefits.
Materials and methods
Patients with an MSK lesion radiologically consistent with a metastases, no previous cancer diagnosis, and no discernible primary tumour were analysed. After biopsy ruled out sarcoma, patients’ tumoural DNA and RNA was analysed using targeted NGS. Data was processed using a custom bioinformatics pipeline and variants classified by biological and clinical significance.
Results
19 patients (8F:11M, median age 70 years, range 40–76) were analysed. 18 (95 %) had ≥1 variant with ‘potential’ or ‘strong’ clinical significance. 8 (42 %) patients' variants highlighted them as eligible for an open clinical trial(s). 3 (16 %) had variant(s) with potential therapeutic or prognostic ramifications. Median cohort survival was 15 months (0–41). 5 of the 11 (45 %) patients referred to an appropriate MDT based on their genomic analysis died during follow up (median survival 11 months, 4–32), compared to 7/8 (88 %) managed by a CUP MDT (median survival 9 months, 0–18).
Conclusion
Our data suggests the real-time genomic analysis of CUP patients has multiple diagnostic and therapeutic benefits. Larger, prospective trials are needed to characterise the genomics of this vulnerable patient cohort, looking for survival benefits of this analysis.

Citation

Eastley, N., Cool, P., Jafri, M., Raghavan, M., & Stevenson, J. (2025). The Genomic Analysis of Patients with Musculoskeletal Metastases from an Unknown Origin. Surgical Oncology, 58, 1-5. https://doi.org/10.1016/j.suronc.2025.102187

• Journal Article Type: Article
• Acceptance Date: Jan 21, 2025
• Online Publication Date: Jan 27, 2025
• Publication Date: 2025-02
• Deposit Date: Apr 16, 2025
• Journal: Surgical Oncology
• Print ISSN: 0960-7404
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 58
• Article Number: 102187
• Pages: 1-5
• DOI: https://doi.org/10.1016/j.suronc.2025.102187
• Keywords: Metastatic bone disease, Cancer unknown primary, Next-Generation Sequencing, Sarcoma, Metastases
• Public URL: https://keele-repository.worktribe.com/output/1054209
• Publisher URL: https://www.sciencedirect.com/science/article/pii/S0960740425000027