檢測關鍵

組織採樣是檢測準確度的關鍵，盡可能採取最大的組織樣本1,2

Limited tissue availability1 Sampling site: metastases are preferred2
  • Single sampling generates a relatively small amount of tissue
    • Sample may contain limited tumor tissue because of the heterogeneity of NSCLC tissue
    • Only one opportunity to fix and process the tissue
  • Amount of tissue available for molecular testing may be limited by priorities of testing:
    1. Histologic diagnosis
    2. IHC for tumor classification
    3. Molecular testing
  • Sampling metastases ensures that the more important fraction of total tumor cell burden is collected
  • This approach also avoids potential heterogeneity problems within the primary tumor 

建議事項：

  1. A number of proposed algorithms have been published based on the advantages and characteristics of individual testing methods1-3
  2. There is no standard diagnostic algorithm1
  3. Shown to the right is one example of a proposed algorithm designed to prevent misdiagnoses3

FDA核准的檢測方法：

Vysis ALK Break Apart FISH Probe
  • Vysis ALK Break Apart FISH Probe Kit
    • First FDA-approved companion diagnostic test for detection of ALK rearrangements in NSCLC
    • Detects ALK rearrangements regardless of fusion partner
Ventana ALK (D5F3) IHC CDx Assay Staining
  • Ventana ALK (D5F3) CDx Assay
    • Fully automated IHC diagnostic test
    • FDA-approved diagnostic test for ALK rearrangements (June 2015); previously approved in Europe (2012) and China (2013)
FoundationOne CDxTM
  • Approved comprehensive genomic profiling test for solid tumor cancers
  • NGS-based in vitro diagnostic that incorporates multiple companion diagnostics including detection of ALK rearrangements in NSCLC
MSK-IMPACTM
  • First FDA-approved laboratory-developed test (2017)
  • NGS-based in vitro diagnostic with a 468-gene oncopanel, including ALK rearrangements
Oncomine Dx6
  • FDA-approved targeted NGS test for NSCLC that detects 368 variants in 23 cancer-associated genes including ALK mutations, but not ALK fusions/translocations

FDA=US Food and Drug Administration; MSK-IMPACT=Memorial Sloan Kettering Integrated Mutation Profiling of Actionable Cancer Targets; ALK=anaplastic lymphoma receptor tyrosine kinase; NSCLC=non–small cell lung cancer; IHC= immunohistochemical; CDx assay=companion diagnostic assay; FISH=fluorescence in situ hybridization; LDT=laboratory-developed test; NGS=next-generation sequencing; RT-PCR=real-time polymerase chain reaction

References:
  1. Tsao MS, et al. IASLC Atlas of ALK and ROS1 Testing in Lung Cancer. Aurora, CO: IASLC Press; 2016.
  2. Thunnissen E, et al. Virchows Arch. 2012;461(3):245-257.
  3. Marchetti A, et al. J Thorac Oncol. 2016;11(4):487-495.
  4. Vysis ALK Break Apart FISH Probe Kit [package insert]. Des Plaines, IL: Abbott Molecular; 2011.
  5. Ventana receives FDA approval for the first fully automated IHC companion diagnostic to identify lung cancer patients eligible for XALKORI® (crizotinib). Tucson, AZ: Ventana Medical Systems Inc; June 15, 2015.
  6. Foundation Medicine. http://investors.foundationmedicine.com/releasedetail.cfm?releaseid= 1050380. Accessed June 13, 2019.
  7. Memorial Sloan Kettering Cancer Center. MSK-IMPACT™ is the first tumor-profiling multiplex panel authorized by the FDA, setting a new pathway to market for future oncopanels [press release]. https://www.mskcc.org/press-releases/msk-impact-first-tumor-profiling-multiplex-panel-authorized-fda-setting-new-pathway-market-future-oncopanels. Accessed June 13, 2019.
  8. Cheng DT, et al. J Mol Diagn. 2015;17(3):251-264.
  9. ThermoFisher Scientific. https://www.thermofisher.com/us/en/home/clinical/diagnostic-testing/condition-disease-diagnostics/oncology-diagnostics/oncomine-dx-target-test/oncomine-dx-target-test-us-only.html. Accessed June 13, 2019.