Introduction

1. Lung cancer is the third most common cancer and the leading cause of cancer-related death in the United States.
2. Two Main Types:
   • Small cell lung cancer: 5-year overall survival (OS) = 7%
   • Non-small cell lung cancer (NSCLC): 5-year OS = 25%
   • Includes: adenocarcinoma, squamous cell carcinoma, large cell carcinoma
     
3. Initial Diagnosis:
• Staging: Provides information regarding tumor size and extent the tumor has spread throughout the body.
• Clinical Workup:
  • Imaging: X-ray, MRI, CT and/or PET scan
    • Including the brain, bones and liver
  • Lung Biopsy: If diagnostic biopsy is an option, enough tissue should be collected to allow for biomarker assessment.
• Tumor Molecular Profiling: Tissue and/or blood biomarkers help guide and optimize a patient’s treatment decisions and outcomes. It is important for tumor biomarker testing to be performed at diagnosis and repeated at time of progression to assess potential mechanisms of acquired resistance, including additional driver mutations that may have developed due to therapy.
  • FISH (fluorescent in situ hybridization): Rapid technique that provides information about tumor DNA.
    • Limitations include tissue depletion, being more difficult to interpret clinically, and not providing information related to fusion partners or positions.
  • IHC (immunohistochemistry): Rapid low-cost technique that provides information related to transcribed and translated events (protein information).
    • Limitations include tissue depletion, being less well-validated, and not providing information related to fusion partners or position.
  • RT-PCR (reverse-transcriptase polymerase chain reaction): Rapid technique with high sensitivity and specificity that provides information related to RNA and can detect specific fusion partners.
    • Limitations include specific primer sets being required for each fusion, inability to detect novel fusion partners, difficulty in extracting high-quality RNA from tumor, and limited multiplexing ability.
  • NGS (next generation sequencing — including RNA and DNA): Technique allows for multiplexing to maximize information obtained from single tissue sample. NGS provides information about targeted DNA and/or RNA locations and/or the whole genome in a single test. It can provide information about fusion partners and identify position.
    • Limitations include higher cost and longer wait time for results.
  • Liquid Biopsy: Noninvasive method for assessing circulating tumor-derived materials — cell-free DNA — from plasma in patients at advanced stages where biopsy is not an option.
    • Limitations include lack of reliability in clinical setting.

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