In the Annals of Oncology, Chinese scholars have published high scores of SCI articles. Where are the highlights of the precise treatment programmes for non-sma
Recently, the international journal of clinical Oncology yearbook of classic Oncology (Annals of Oncology, SCI impact factor 11.855) in the form of essay (Letter) published the second affiliated hospital of guangzhou medical university professor Li Yuqing joint Shanghai w biological technology co., LTD. (w medical) in non-small cell lung cancer treatment of the latest research results, this is also China's clinical experience in the field of international cancer targeted therapy of lung cancer and a high-quality display, ortega medical circulating tumor DNA (ctDNA) the second generation of gene sequencing technology (NGS) are won the international peer recognition.
Professor li is dedicating to TKIs drug resistance in clinical treatment and research, this case with ctDNA published clinical practice of the second generation sequencing cancer surveillance and guidance personalized medicine have clinical significance.
Summary of the article
A 36-year-old smokeless history of Chinese women in June 2016 diagnosed with lung adenocarcinoma IV, along with multiple metastases, chemotherapy is invalid, ctDNA detection showed that patients with EGFR L858R variation and augmentation, for after he began to adopt it in early July, the clinical symptom significantly reduced, brain metastases disappear (CR), lung and liver lesions narrowing (PR).
Disease progression six months later;
The second ctDNA test results showed that the new c-met increased in the patients, and then the combination of erlotinib and chazolinib combined with drugs, the clinical symptoms were relieved, and the lung lesions were significantly reduced.
After 9 weeks of combined use, the patient developed the disease again.
The results of the third ctDNA test showed that the new NRAS Q61H and KRAS G12D variation were found in the patients.
The MET amplification was not detected, but an unreported missense mutation of the MET G1108C was detected.
The G1108 residues were located in the binding area of the MET kazolinib, which could affect the drug combination and lead to the drug.
The article highlights
Highlight 1: erlotini/kezolitinib has a significant effect and is clinically feasible
CtDNA in patients with second generation sequencing and gene amplification and detection of EGFR L858R mutations and secondary c - MET after amplification, start it for ni/g azole for combination, after cough reduce patients, clinical symptoms, the decline in serum carcinoma, and lung lesions significantly reduced.
Figure 1. CT images of the pulmonary primary and posterior CT images
Highlight 2: new xazolinib potential drug resistance site, MET G1108C mutation
After erlotini/kezolitinib combined with drug resistance, ctDNA ii sequenced an unreported missense mutation of the MET G1108C.
The analysis of the three-dimensional structure of proteins revealed that G1108 residual base was located near the binding site of c-met and kezolitinib, which could affect the combination of drugs, which could lead to the drug.
Figure 2. A three-dimensional simulation of MET - kazolinib
Highlight 3: erlotinib has a significant effect on brain lesions
In the second generation of ctDNA, EGFR L858R and gene amplification were detected, and the clinical symptoms were rapidly relieved after taking erlotinib, especially in the brain metastasis (CR, fig.3).
This indicated that erlotini had a good brain effect and a significant effect on EGFR mutant positive lung cancer.
However, throughout the patient's entire course of illness, the EGFR variation abundance has been at a high level in the progress of the disease, and the effect of erlotinib on the treatment of other EGFR positive lesions still needs further study and discussion.
Figure 3. MRI images of the brain metastases before and after the use of kezoteni
Highlight 4: detection of gene copy number change (CNV) in ctDNA through the second generation gene sequencing is feasible
In this case, CNV was detected multiple times in the second generation of ctDNA, and the corresponding drug regimen was also received with the expected clinical response.
This indicates that ctDNA second-generation sequencing detection technology can realize the accurate analysis of CNV, and has valuable reference value for the clinical medication of patients.
Highlight 5: ctDNA ii sequencing can accurately and accurately reflect the mutation of patients in real time
CtDNA has the advantages of non-invasive and easy to acquire, and it plays a key role in the critical nodes of drug resistance and disease progression, which can assist in the timely adjustment of the drug regimen and the tumor monitoring.
Second-generation sequencing has the advantages of high throughput, sensitive detection and no need to know the nucleic acid sequence in advance, so as to assist the clinical detection of new tumor resistance mechanism and realize the bidirectional transformation of clinical research.
CtDNA testing plays an irreplaceable role in the clinical guidance and drug resistance detection of patients.
However, the total number of ctDNA is relatively small, and the tumor type, location, stage and so on are relatively large, and the fragments are shorter and the half-life is shorter, and the detection is very difficult.
In this study, the method is used to capture the technology and improve the noise reduction of the raw letter algorithm, which greatly improves the detection rate and the accuracy of the result.
After optimization, the detection effect of the second generation of ctDNA sequencing for different mutation types is as follows:
About the journal Annals of Oncology:
Annals of Oncology, tumor by the European medical association of tumor and the Japanese medicine association, is published by Oxford University of peer review of the nature of clinical medical journal, published mainly basic research is of great significance in clinical Oncology and tumor of new medical research, review articles, etc.
In 2016, the latest data show that the journal IF has reached 11.855, among the top 10 journals in the 300-plus oncology field, one of the top SCI journals.