The genomic analysis of patients with musculoskeletal metastases from an unknown origin

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.