Editor's note: With the rapid development of precision medicine, the European Society of Oncology (ESMO) Precision Medicine Working Group has recently updated its guidance on next-generation sequencing (NGS) of tumors in patients with advanced cancer in routine clinical practice. In this issue, Professor Xu Hao from the First Affiliated Hospital of Nanjing Medical University will give us an in-depth interpretation of the latest recommendation released by the ESMO Precision Medicine Working Group in 2024: Correlation Analysis of Circulating Tumor DNA (ctDNA) and Gastrointestinal Stromal Tumor (GIST) Tumor Volume.
Expert presentation
Xu Hao
Chief physician, associate professor, master's supervisor
Deputy Director of the Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University
Member of the Gastric Cancer Professional Committee of the Chinese Anti-Cancer Association
Vice Chairman of the Youth Committee of the Gastrointestinal Stromal Tumor Diagnosis and Treatment Committee of the Surgeon Branch of the Chinese Medical Doctor Association
Member of the Gastrointestinal Stromal Tumor Professional Committee of the Chinese Anti-Cancer Association
Member of the Gastrointestinal Stromal Tumor Expert Committee of the Chinese Society of Clinical Oncology (CSCO).
He is a member of the Upper Gastrointestinal Tract Tumor Professional Committee of the Chinese Association of Research Hospitals
Vice Chairman of the Gastrointestinal Stromal Tumor Committee of Jiangsu Anti-Cancer Association
Member of the Surgery Branch of Jiangsu Medical Association
Deputy head of the Surgical Nutrition Group of the Surgery Branch of Jiangsu Medical Association
Director of Jiangsu Anti-Cancer Association
Specialty: Comprehensive treatment of gastric cancer and gastrointestinal stromal tumors
summary
Patients with gastrointestinal stromal tumors (GIST) who are treated with tyrosine kinase inhibitors require monitoring and evaluation with regular CT examinations, which exposes the patient to the accumulation of radiation. This exploratory study aims to assess ctDNA levels to monitor tumor response to treatment and to compare changes in ctDNA levels to RECIST 1.1 and total tumor volume measurements. Between 2014 and 2021, this study included 6 GIST patients with mutations in the KIT proto-oncogene, KIT exon 11, and long-term plasma samples were prospectively collected. ctDNA levels of relevant plasma samples were determined using a KIT 11 exon digital droplet PCR titration. Tumor volume measurement is performed using a semi-automated method. In this study, ctDNA levels were actually analyzed in 94 out of 130 samples from the clinic. ctDNA was undetectable in patients with a clear response to treatment; ctDNA is detectable in 5/6 of patients at the time of disease progression. The higher the ctDNA level, the larger the tumor volume. Undetectable ctDNA at the time of disease progression is consistent with a smaller tumour volume on imaging compared with detectable ctDNA. In summary, ctDNA levels appear to correlate with total tumor volume at the time of disease progression. Our exploratory study shows that ctDNA testing has the potential to be an indicator of treatment follow-up.
Brief comment on
ctDNA is an important part of liquid biopsy, which has a short half-life in the blood and can better reflect the dynamic changes of tumors. In this study, a total of 6 patients were included in ctDNA as a hematological index to measure the copy number level of KIT exon 11 mutations and compare them with traditional imaging examinations to explore the effectiveness of the two methods in evaluating the response to drugs, the change in tumor volume and the prognosis of patients after receiving drug therapy. In general, the increase of ctDNA index has a certain correlation with the increase of GIST tumor volume, which can reflect the patient's response to drugs to a certain extent. As a non-invasive test, ctDNA is a relatively simple, safe and convenient examination method without the potential hidden danger of radiation accumulation, and it has been relatively accurately applied in other tumors, and it also has broad prospects in GIST.
However, to more closely integrate ctDNA with tumor progression and patient prognosis, more and more rigorous data are needed. First of all, the relationship between ctDNA and tumor volume is obviously more close, and when the tumor volume is large, ctDNA is more sensitive, and the change of tumor volume can be evaluated through its value, and then the tumor response to drugs can be judged. However, when the tumor is small, ctDNA is often undetectable or does not reflect the patient's disease progression through effective numerical changes, even if the tumor has progressed on imaging. At present, ctDNA can be used as a relatively effective adjunct to PD patients with large tumors, but for larger tumors, imaging examination itself can better visually reflect PD masses. Secondly, ctDNA is greatly affected by a variety of factors, such as surgery and drugs. It can be seen in the article that the growth of ctDNA is sometimes more sensitive, preceding the change of imaging, but due to the confounding of many factors, the author cannot make this conclusion. Finally, in order to widely use ctDNA after GIST treatment, it is necessary to have more patient cases for data support and multi-level and multi-factor analysis, and it is expected that more clear and scientific relevant data statistics will be obtained after the subsequent expansion of the sample, so as to bring a more economical, safe and effective evaluation scheme for patients after GIST treatment.
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