Molecular Pathology Detection of Lung Cancer in China

"The molecular variation spectrum of NSCLC patients in China is different from the Western population.
It is mainly manifested in lung adenocarcinoma.
Which are the mandatory genes? Which are the extended genes?" In January 2021, the Journal of the National Cancer Center (JNCC) was launched and published the latest China Cancer Epidemic Data: "China Cancer Incidence and Mortality in 2015", the data shows that in 2015 there were 3.
929 million new cancer cases and 2.
338 million deaths in China.
Among them, the incidence of lung cancer (787,000 cases) and mortality (631,000 cases) ranks first among all cancers; non-small cell lung cancer (NSCLC) is the main pathological subtype of lung cancer, accounting for about 85%, mainly including lung adenocarcinoma, lung squamous cell carcinoma and large cell carcinoma; With the rapid development of NSCLC targeted therapy and immunotherapy, the 5-year survival rate of advanced NSCLC has increased from less than 5% to 16%
.

At the same time, more and more molecular markers (such as RET, NTRK, TMB, etc.
) have emerged.
Molecular typing based on genes or genomics will gradually surpass the traditional pathological histomorphological typing and become the key to accurate clinical tumor diagnosis and treatment.
Link (Physicians need to guide clinical diagnosis and treatment plans based on molecular pathology testing results); In April 2021, the Chinese Journal of Pathology, Volume 50, Issue 4, published the "Clinical Practice Guidelines for Molecular Pathology Testing of Non-small Cell Lung Cancer (2021 Edition)".
The guidelines are based on domestic clinical practice data and domestic marketed therapeutic drugs, etc.
, to formulate clinical practice guidelines for NSCLC molecular pathology detection that are more in line with China's national conditions; NSCLC molecular pathology detection mainly includes targeted therapy and immunotherapy; targeted therapy related Refer to the table below for molecular pathology testing; *Supplementary information: Domestic third-generation EGFR-TKIs vomitinib has been approved by the NMPA conditional approval in March.
The molecular variation spectrum of NSCLC patients in China is different from that of the Western population.
It is mainly reflected in lung adenocarcinoma (lung squamous cell carcinoma).
Currently, there is no clear genetic testing site and approved molecular targeted drugs)
.

For example, EGFR mutation frequency 45%~55% ALK rearrangement/fusion mutation frequency 5%~10% ROS1 rearrangement/fusion mutation frequency 2%~3% MET ex14 skip mutation frequency 2%~4% (the above are mandatory genes ) MET amplification mutation frequency 3%~19% HER2 mutation frequency 2%~4% BRAF V600 mutation frequency 1%~2% RET rearrangement/fusion mutation frequency 1%~4% KRAS mutation frequency 8%~10% NTRK, NRG1/2, FGFR2 rearrangement/fusion mutation frequencies are all <1%, etc.
(the above are extended genes).
Except for a few cases of co-mutation, the above gene mutations are generally mutually exclusive in the same case; immunotherapy-related molecular pathology See the table below for detection; mainly include PD-L1 protein expression and tumor mutational burden (TMB), other biomarkers, such as high microsatellite instability (MSI-H), are rare in NSCLC (current immunotherapy is mainly used for EGFR , NSCLC patients with negative ALK and ROS1 gene mutations); In recent years, the detection of lung cancer MRD (molecular/minimal residual disease) has received extensive clinical attention
.

On March 6, 2021, the 18th Lung Cancer Summit reached my country’s first "Consensus on the Detection and Clinical Application of Lung Cancer MRD".
At present, the clinical application and detection of MRD need to be further verified and standardized; NSCLC molecular pathology detection is often submitted for inspection What are the sample types? 1) Tumor tissue paraffin specimens: including specimens obtained by surgery and puncture; 2) Cytology specimens: including pleural effusion (supernatant is better than sediment cells), puncture biopsy, alveolar lavage fluid, etc.
(made into paraffin embedded Specimens, evaluate the proportion of tumor cells); 3) Liquid biopsy specimens: routinely select blood, such as meningeal metastasis, select cerebrospinal fluid; commonly used clinical molecular pathology detection methods for NSCLC include Sanger sequencing (cannot fully meet clinical needs), RT-PCR method , FISH method, IHC method and NGS method, each has its own advantages and disadvantages, and can be selected according to clinical needs; *For patients with advanced lung adenocarcinoma with negative driver genes detected by traditional methods, NGS testing is recommended.
It should be noted that for Gene rearrangement/fusion.
In rare cases, gene rearrangements detected at the DNA level (such as the rearrangement of intergenic regions) may not cause the expression of fusion proteins.
DNA+RNA combined detection has high sensitivity And specificity: Compared with traditional detection methods, NGS can detect mutations, rearrangements and amplifications of multiple target genes at the same time, thereby effectively avoiding sample waste, saving detection time and relatively reducing detection costs
.

Therefore, NGS can be used to detect all mandatory and expanded molecular targets of NSCLC in newly treated patients.
NGS is also recommended for drug-resistant patients to find the cause of drug resistance.
The detection method is re-examined at the RNA or protein level); In January 2020, "Lung Cancer" published a performance comparison and cost-benefit analysis of NGS panel and traditional detection methods in Asian NSCLC patients.
The results showed that: compared with sequential detection Compared with strategies, the first choice NGS test is a feasible, cost-effective molecular pathology test method, and supports the implementation of NGS test in Asian non-squamous NSCLC patients, so that patients can get the most suitable personalized treatment (compared with traditional test methods).
Compared with direct NGS testing, the cost is lower, and it can increase the number of patients suitable for targeted therapy by 5%); NGS testing results are transformed into individualized and precise diagnosis and treatment plans for patients, which need to be based on the interpretation of complex results and the interpretation of reports.
MDT It may not be able to meet the growing demand for interpretation of genetic testing reports in lung cancer clinics (especially a variety of potential treatment options after drug resistance); "Chinese Expert Consensus on Clinical Application of Second-Generation Sequencing Technology in NSCLC (2020 Edition)" pointed out that NGS technology Bringing more and more comprehensive gene mutation information to NSCLC patients, and advocating the establishment of NSCLC-MTB (Molecular Tumor Expert Committee) to correctly interpret the results of genetic testing and make individualized clinical treatment decisions; "Guidelines for Interpretation of NGS Clinical Reports" "It also pointed out that for complex situations, multidisciplinary discussions (such as Molecular Tumor Board, MTB) should be encouraged to analyze the biological and clinical significance of different combinations of mutations; MTB (Molecular Tumor Board), the molecular tumor expert Committee; there are already relevant management practices abroad: it is recommended to carry out cancer gene panel testing for cancer patients and submit it to the molecular tumor expert committee (MTB) (A-level recommendation); regional affiliates or outreach agencies may consider discussing risks and On the basis of benefits, submit cases to MTB (recommendation of grade C is required); MTB is just needed for precise diagnosis and treatment of lung cancer (tumor)! Article source: Gene Talks References: 1.
Zhang SW, Sun KX, Zheng RS, Zeng HM, Wang SM, Chen R, Wei WQ, He J.