Interview with Professor Guan Tao: Analysis of the clinical value of ctDNA in the new diagnosis of diffuse large B-cell lymphoma

Edited and sorted out by Yimaitong, please do not reprint
without authorization.

The 2022 European Society for Internal Oncology (ESMO) Annual Meeting was held
in Paris from September 9 to 13 local time.
On September 12, at the Mini Oral session on hematological tumors, the results of several studies were announced
.
Professor Guan Tao of Shanxi Provincial Cancer Hospital reported the results of a retrospective analysis of the clinical value of ctDNA in the new diagnosis of diffuse large B-cell lymphoma (DLBCL), and Professor Guan Tao was invited by Yimaitong to be interviewed to talk about the main results and significance
of the study.

Congratulations to you and your team for your research "Retrospective Analysis of the Clinical Value of ctDNA in Newly Diagnosed DLBCs" was selected in the Mini Oral section of 2022 ESMO, first of all, I would like to briefly introduce ctDNA, what are the advantages and disadvantages of ctDNA testing compared to PET-CT?

Professor Guan Tao: Speaking of circulating tumor DNA (ctDNA), the first thing to understand is free DNA, free DNA is stable in the peripheral blood plasma, it is the DNA molecule released into the peripheral blood after apoptosis, when the human body has tumors, the DNA after the death of tumor cells will also be released into the peripheral blood, and the DNA molecule released to the peripheral blood of the tumor source is the circulating tumor DNA
.

PET-CT is very important for the evaluation of DLBCL before treatment and the evaluation of efficacy after treatment, and ctDNA also has the role of judging prognosis before treatment and judging efficacy after treatment, and its advantage is that it can better reflect the overall situation of the tumor in vivo and weaken the problem of tissue source heterogeneity of the tumor in vivo; The genetic information carried by ctDNA can also be used for the fine molecular typing of DLBCL, the selection of targeted drugs, and the judgment of disease transformation; In addition, the methodology of ctDNA is more sensitive, the current commonly used ctDNA detection methods include targeted sequencing, digital PCR, etc.
, these methods can make the detection sensitivity up to 10-5-10-6, there are also case reports, ctDNA can be found 2 months before the diagnosis of ^PET-CT lymphoma recurrence
。 Of course, the application of ctDNA also has its disadvantages, the most important is the problem of standardized (methodological) detection, and the need to do more prospective clinical trials to ensure that ctDNA can be used clinically to help doctors and patients
.

Meyimai: What are the results of this retrospective study? What is the clinical value of ctDNA in the new diagnostic DLBCL?

Professor Guan Tao: ctDNA can provide at least two aspects of information, one is genetic change information, including gene mutations, translocations, deletion and amplification of short fragments, etc.
; On the other hand, there are many ways to quantify genes, and there are many ways to calculate quantitatively, and our study chose the VAF average, that is, the average
of the mutation frequency.
The results of this study demonstrate that ctDNA quantification can reflect pre-treatment DLBCL tumor load, which is closely related to some common prognostic indicators, such as the higher the IPI score, the higher the VAF mean, the higher the Ann Arbor stage, and the higher the VAF mean; VAF averages were also found to be higher
in patients with high LDH, bone marrow invasion, and patients with large masses.
In addition, the VAF mean can also determine the prognosis, and the overall survival and progression-free survival of patients with high VAF mean are both worse than those
with low VAF mean.

We also found the clinical value of PCLO genes, in China, the frequency of PCLO gene mutations is very high, more than 30%, different from the data
of Western countries.
At the same time, PCLO gene mutations also have the significance of prognostic judgment, and patients with PCLO gene mutations have worse survival than patients without PCLO gene mutations
.

In summary, the detection of ctDNA before treatment as a non-invasive test can be used to determine tumor burden and predict treatment response and prognosis
.

Medical Pulse Pass: At present, what other explorations does ctDNA have in other tumor species? The result? What are your perspectives for the future use of ctDNA and other liquid molecular markers in lymphoma?

Professor Guan Tao: There are also many exploratory studies on ctDNA in other tumor species, such as lung cancer, breast cancer, colorectal cancer and pancreatic cancer, etc.
, which have proved that ctDNA has clinical value as a biomarker for tumor management in other tumors, including pre-treatment disease assessment, monitoring treatment response, residual lesion detection, predictive survival and guidance treatment
。

There are many fields of application of ctDNA in lymphoma that can be explored, in addition to genetic information, ctDNA also includes a lot of epigenetic information, such as methylation, DNA methylation can lead to disturbances of gene expression or genome instability, resulting in tumor occurrence, if you can explore epigenetic information from ctDNA has certain clinical value
.
In addition to circulating DNA molecules, other liquid biopsy analytes, such as circulating tumor cells, circulating microRNAs, tumor-affected platelets, or tumor-associated proteins, may provide additional information
on tumor evolution and treatment response in cancer patients.
Studies related to plasma free DNA (cfDNA) have also shown clinical potential for early detection of virus-associated cancers, such as information on DNA associated with Epstein-Barr virus in peripheral T-cell lymphoma in free DNA
.
Finally, a growing body of data suggests that other non-blood-based fluid biopsy methods, such as saliva, cerebrospinal fluid, or urine, can be reliably incorporated into future clinical trials
.

Professor Guan Tao

Ph.
D.
in Molecular Biology, Research Assistant

The head of the hematology department of Shanxi Provincial Cancer Hospital, specializing in the laboratory diagnosis of hematology

Member of the Standing Committee of the Hematology Branch of Shanxi Medical Association

Director General of Cellular Immunology Professional Committee of Shanxi Medical Doctor Association

Director General of the Hematology Professional Committee of Shanxi Association of Women Physicians

Member of the Standing Committee of the Blood Branch of the Shanxi Geriatrics Association

Member of the Standing Committee of the Endocrine Metabolism Immunology Committee of the Shanxi Society of Immunology

He is a member of the Microbiology and Immunology Professional Committee of Shanxi Medical Association

Member of the Standing Committee of the Chinese Clinical Flow Cytometry Alliance (CFCF).

Member of the lymphoma group of the Biotherapeutics Professional Committee of the Chinese Research Hospital Association