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

  • 0The Royal Orthopaedic Hospital, Birmingham, UK; The University of Leicester, Leicester, UK.
Surgical Oncology +

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February 6, 2025

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February 6, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

Next Generation Sequencing (NGS) of metastatic cancer in patients with no known primary tumor identified actionable mutations. This genomic analysis offers diagnostic and therapeutic benefits, improving survival outcomes for this challenging patient group.

Area Of Science

  • Oncology
  • Genomics
  • Translational Medicine

Background

  • Patients with metastatic cancer of unknown primary (CUP) have limited treatment options and poor prognosis.
  • Musculoskeletal metastases without a detectable primary tumor represent a significant clinical challenge.
  • Current management for CUP often lacks disease-specific therapeutic strategies.

Purpose Of The Study

  • To investigate the diagnostic, therapeutic, and prognostic utility of targeted Next Generation Sequencing (NGS) in patients with unknown primary (CUP) cancer presenting with musculoskeletal metastases.
  • To assess the feasibility and impact of real-time genomic profiling in guiding treatment decisions for CUP patients.
  • To evaluate potential survival benefits associated with genomic-guided management.

Main Methods

  • Prospective pilot study analyzing tumor DNA and RNA from patients with radiologically confirmed metastases and no discernible primary tumor.
  • Exclusion of sarcoma via biopsy, followed by targeted Next Generation Sequencing (NGS) of tumor samples.
  • Bioinformatic analysis of NGS data, classifying variants by clinical and biological significance.

Main Results

  • 19 patients with unknown primary cancer and musculoskeletal metastases were analyzed.
  • 95% of patients had clinically significant genomic variants identified.
  • 42% of patients were identified as eligible for targeted clinical trials based on NGS results.
  • Genomic-guided multidisciplinary team (MDT) management showed a trend towards improved median survival (11 months) compared to standard CUP MDT (9 months).

Conclusions

  • Real-time genomic analysis of unknown primary cancer (CUP) patients offers significant diagnostic and therapeutic advantages.
  • Targeted NGS can identify actionable mutations, potentially improving treatment selection and patient outcomes.
  • Larger prospective studies are warranted to confirm the survival benefits of genomic profiling in this vulnerable patient population.

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