Chromosomal abnormalities
FFPE tissue
6–8 slides of 7–10 μm sections
Chromo-
somal
abnor-
malities
FFPE tissue
6–8 slides of 7–10 μm sections
Tissue testing can be ordered for diagnosis, staging, and to identify actionable and emerging biomarkers5*
The primary purpose of specimens intended for initial diagnoses is to make an accurate diagnosis and preserve tissue for molecular studies
In resection specimens, the primary purpose is to classify the histologic subtype and determine staging5*
Broad molecular profiling should be carried out on samples to help identify patients that may be eligible for targeted therapies5*
Serial biopsies to track tumor evolution and response to therapy can be helpful in informing treatment decisions, but can carry challenges, including complications from invasive diagnostic procedures6
The primary purpose of specimens intended for initial diagnoses is to make an accurate diagnosis and preserve tissue for molecular studies
In resection specimens, the primary purpose is to classify the histologic subtype and determine staging5*
Broad molecular profiling should be carried out on samples to help identify patients that may be eligible for targeted therapies5*
Serial biopsies to track tumor evolution and response to therapy can be helpful in informing treatment decisions, but can carry challenges, including complications from invasive diagnostic procedures6
Tissue insufficiency in NSCLC impacts biomarker testing, as there is often only a small amount of sample available for comprehensive biomarker analysis.
This challenge can impact disease management and the identification of patients that may be eligible for targeted therapies6–8
Technical Considerations6,8
Tissue quantity and quality can vary across patient cases, making testing difficult
- <30% of NSCLCs are resectable at the time of presentation; therefore, most clinical samples available for testing are small and generally include FFPE or cytology specimens
- 10–20% of biopsies are inadequate for molecular testing due to insufficient tissue or amplifiable DNA
- Biopsy specimens are exhausted for other diagnostic purposes
- Although the number of biomarkers for testing has increased in NSCLC, tumor sampling has generally moved towards less invasive procedures, which yield smaller amounts of sample
Patient Considerations6
Tissue from patients may not be available for testing due to a variety of reasons
- Patients may not have enough tissue for molecular testing
- Patients may lack biopsy amenable lesions
- Patients may not want to go through repeat biopsies due to potential risks or complications from invasive procedures
Disease Impact5
Inability to perform testing due to tissue insufficiency may impact disease management:
- Diagnosis
- Understanding of tumor biology
- Treatment selection
- Evaluation of treatment response
- Evaluation of disease progression
Technical Considerations6,8
Tissue quantity and quality can vary across patient cases, making testing difficult
- <30% of NSCLCs are resectable at the time of presentation; therefore, most clinical samples available for testing are small and generally include FFPE or cytology specimens
- 10–20% of biopsies are inadequate for molecular testing due to insufficient tissue or amplifiable DNA
- Biopsy specimens are exhausted for other diagnostic purposes
- Although the number of biomarkers for testing has increased in NSCLC, tumor sampling has generally moved towards less invasive procedures, which yield smaller amounts of sample
Patient Considerations6
Tissue from patients may not be available for testing due to a variety of reasons
- Patients may not have enough tissue for molecular testing
- Patients may lack biopsy amenable lesions
- Patients may not want to go through repeat biopsies due to potential risks or complications from invasive procedures
Disease Impact6
Inability to perform testing due to tissue insufficiency may impact disease management:
- Diagnosis
- Understanding of tumor biology
- Treatment selection
- Evaluation of treatment response
- Evaluation of disease progression
NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Non-Small Cell Lung Cancer (Version 3.2023) recommend broad molecular profiling to minimize tissue use and potential wastage in NSCLC5*
A major limitation in obtaining tissue molecular testing results for NSCLC occurs when minimally invasive techniques are used to obtain samples
- The yield may be insufficient for molecular, biomarker, and histologic testing
- HCPs should procure sufficient tissue to enable all appropriate testing
When tissue is minimal, laboratories should deploy techniques to maximize tissue for molecular and ancillary testing
- This includes dedicated histology protocols for:
- Small biopsies
- Peripheral blood (plasma ctDNA), which can be a surrogate sample to identify oncogenic driver mutations
Recommended biomarker testing in NSCLC includes:
- Broad molecular profiling using NGS, Sanger sequencing, RT-PCR, FISH
- PD-L1 testing using IHC
NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Non-Small Cell Lung Cancer (Version 3.2023) recommend broad molecular profiling to minimize tissue use and potential wastage in NSCLC5*
A major limitation in obtaining tissue molecular testing results for NSCLC occurs when minimally invasive techniques are used to obtain samples
- The yield may be insufficient for molecular, biomarker, and histologic testing
- HCPs should procure sufficient tissue to enable all appropriate testing
When tissue is minimal, laboratories should deploy techniques to maximize tissue for molecular and ancillary testing
- This includes dedicated histology protocols for:
- Small biopsies
- Peripheral blood (plasma ctDNA), which can be a surrogate sample to identify oncogenic driver mutations
Recommended biomarker testing in NSCLC includes:
- Broad molecular profiling using NGS, Sanger sequencing, RT-PCR, FISH
- PD-L1 testing using IHC
References
- Michaels E, Bestvina CM. Meeting an un-MET need: targeting MET in non-small cell lung cancer. Front Oncol. 2022;12:1004198. doi:10.3389/fonc.2022.1004198
- Mino-Kenudson M. Immunohistochemistry for predictive biomarkers in non-small cell lung cancer. Transl Lung Cancer Res. 2017;6(5):570-587. doi:10.21037/tlcr.2017.07.06
- Tsao MS, Yatabe Y. Old soldiers never die: is there still a role for immunohistochemistry in the era of next-generation sequencing panel testing? J Thorac Oncol. 2019;14(12):2035-2038. doi:10.1016/j.jtho.2019.09.007
- List of cleared or approved companion diagnostic devices. US Food and Drug Administration. Updated August 21, 2023. Accessed August 22, 2023. https://www.fda.gov/medical-devices/in-vitro-diagnostics/list-cleared-orapproved-companion-diagnostic-devices-in-vitro-and-imaging-tools
- Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.3.2023. © National Comprehensive Cancer Network, Inc. 2023. All rights reserved. Accessed August 10, 2023. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
- Liam CK, Mallawathantri S, Fong KM. Is tissue still the issue in detecting molecular alterations in lung cancer? Respirology. 2020;25(9):933-943. doi:10.1111/resp.13823
- Fox AH, Nishino M, Osarogiagbon RU, et al. Acquiring tissue for advanced lung cancer diagnosis and comprehensive biomarker testing: a National Lung Cancer Roundtable best-practice guide. CA Cancer J Clin. 2023;73(4):358-375. doi:10.3322/caac.21774
- Kim L, Tsao MS. Tumour tissue sampling for lung cancer management in the era of personalised therapy: what is good enough for molecular testing? Eur Respir J. 2014;44(4):1011-1022. doi:10.1183/09031936.00197013
