Implication of Biomarker Mutations for Predicting Survival in Patients With Metastatic Lung Cancer to the Spine

Spine (Phila Pa 1976). 2018 Nov 1;43(21):E1274-E1280. doi: 10.1097/BRS.0000000000002683.

Abstract

Study design: A retrospective cohort study.

Objective: We performed a retrospective study of patients treated at our institution over the last 7 years to ascertain whether gene expression signatures in patients with advanced metastatic disease are associated with survival, when the disease has progressed to the spine.

Summary of background data: Spinal metastases are a major cause of morbidity in patients with cancer. Molecular profiling strategies to characterize lung cancer have identified several genetic biomarkers that may lead to more effective prognostication.

Methods: We queried our institutional database for patients with metastatic lung cancer who underwent treatment for spinal metastases between 2011 and 2017. Genetic mutations in ALK, MET, ROS1, EGFR, and KRAS were chosen a priori for study based on availability by standard SNaPshot Lung Tumor Genotyping Analysis. Survival time was the duration between treatment for spinal metastases and death. Kaplan-Meier methods and the log-rank test were applied to characterize survival data.

Results: Twenty-six patients met criteria for inclusion. Median survival after surgery was 0.67 years. Median overall survival (OS) after diagnosis was 2.7 years. The presence of molecular abnormalities in patients with spinal metastases was significantly associated with increased OS (HR 0.38, 95% CI 0.12-1.22, P = 0.03).

Conclusion: Molecular phenotyping may provide prognostic insight in patients undergoing surgery for spinal metastases. This is the first study to demonstrate an association between genetic mutational data and OS in this patient population. It also represents the largest published series of such patients (n = 26) for which genetic mutational data are reported. Future models estimating survival for patients with spinal metastases may be enhanced by incorporation of molecular criteria.

Level of evidence: 4.

MeSH terms

  • Adult
  • Aged
  • Anaplastic Lymphoma Kinase / genetics
  • Biomarkers
  • ErbB Receptors / genetics
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology*
  • Male
  • Middle Aged
  • Mutation
  • Prognosis
  • Protein-Tyrosine Kinases / genetics
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins c-met / genetics
  • Proto-Oncogene Proteins p21(ras) / genetics
  • Retrospective Studies
  • Spinal Neoplasms / secondary*
  • Spinal Neoplasms / surgery
  • Survival Rate
  • Transcriptome

Substances

  • Biomarkers
  • KRAS protein, human
  • Proto-Oncogene Proteins
  • Anaplastic Lymphoma Kinase
  • EGFR protein, human
  • ErbB Receptors
  • MET protein, human
  • Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins c-met
  • ROS1 protein, human
  • Proto-Oncogene Proteins p21(ras)