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<h1 toutiao-origin="h3" >What "Zhongshan characteristics" will this year's Zhongshan Lung Cancer Forum bring? </h1>
From October 8 to 10, 2021, the 7th Zhongshan Lung Cancer Forum was successfully held in Shanghai, during which the "Medical Oncology Channel" set up a special scene of famous doctor Kung Fu Tea, and specially invited Professor Zhang Xin of Zhongshan Hospital Affiliated to Fudan University to discuss and share issues related to intestinal flora and lung cancer immunotherapy.
Solid scientific research results sharing,
Explore the unknown
"The relevant topics shared by the Zhongshan Lung Cancer Forum in the past include the relationship between the abundance and efficacy of EGFR mutations, the relationship between tumor heterogeneity and lung cancer treatment, and the discussion of the high accuracy of bronchoscopy and genetic testing.
Research has never stopped, many studies have shown that there is a certain relationship between the intestinal microbiota and immunotherapy for lung cancer, but many doctors still lack systematic understanding of it, and our team is conducting joint research with the gastroenterology department. This forum focused on sharing and discussing the essence of relevant scientific research. When referring to the original intention of sharing the topic of this forum, Professor Zhang Xin said so.
Everything is ready, only the east wind is owed,
Patient recognition is the biggest motivator
The fundamental purpose of the study is to apply it to clinical practice.
In February, Science released a Phase I clinical study showing that fecal flora transplantation (FMT) improves resistance to PD-1 monoclonal antibodies in patients with melanoma.
Another study, also published in Science, showed that FMT in combination with PD-1 monoclonal antibody therapy benefited patients with PD-1 monoclonal antibody-resistant melanoma. These results are stunning and provide guidance for follow-up studies of intestinal flora and immunotherapy.
"The first discovery in 2015 that the gut microbiota can affect the efficacy of immune checkpoint inhibitors against tumors; a 2018 clinical study found that the use of antibiotics within 30 days of initiation of tumor immunotherapy significantly shortened progression-free survival (PFS) and overall survival (OS). A number of other blockbuster studies have confirmed that patients with tumors with high microbial diversity are more effective in receiving immune checkpoint inhibitors.
Inspired by the relevant research and reports on the association of immunotherapy with the intestinal microbiota, our team and the gastroenterology team decided to carry out the corresponding Phase I study.
Initially, the focus was more on safety and initial efficacy. Unlike other previous studies, our team and the Gastroenterology team jointly conducted research in the direction of immunotherapy for non-small cell lung cancer (NSCLC). Professor Zhang Xin talked about a study on intestinal flora jointly conducted by the two teams.
It is worth mentioning that there are some special points in the research on intestinal flora carried out by Professor Zhang Xin's team and the gastroenterology team of Zhongshan Hospital Affiliated to Fudan University, Professor Zhang Xin shared: "The research needs to conform to the general trend, and the first-line treatment of clinical lung cancer patients mostly adopts combination treatment regimens, such as the combination of chemotherapy and immunotherapy. Therefore, this study is designed to take this situation into account, in line with the general trend of combination therapy.
In addition, patients included in previous relevant studies are selective and may be groups of patients who are effective for immunotherapy.
This study explores healthy people. We extract healthy intestinal flora through a comprehensive physical examination of college students. At first, it was worried that clinical patients did not accept FMT as a treatment, but it is gratifying that many patients accept and recognize the therapy. This also gives researchers and clinicians more motivation and encouragement to carry out more follow-up research. ”
Seemingly unrelated, it is actually far-reaching
Intestinal flora exists in large quantities in the human body, and as relevant research continues to deepen, researchers have found that some diseases are closely related to the intestinal flora. Previous studies have found that diseases such as Alzheimer's disease and ADHD are associated with the intestinal flora.
Professor Zhang Xin analyzed the reasons why lung cancer and other diseases are associated with the intestinal microbiota: "The correlation is not known, which is bound to cause heated discussion and strong repercussions. Lung cancer and intestinal flora seem to be difficult to associate together, but in recent years, immunotherapy has developed in a spurt, a large number of lung cancer patients apply immunotherapy, so from basic research to clinical research, a series of studies have shown that intestinal flora and lung cancer immunotherapy efficacy side effects, and even reverse drug resistance are closely related. ”
In the study of the association between lung cancer immunotherapy and the gut microbiota, the more impressive study included an animal study in which researchers used antibiotics to empty the intestinal flora in animals and then gave immune checkpoint inhibitors. Unexpectedly, the experimental animals were almost completely drug-resistant. The researchers began to analyze previous relevant clinical studies to determine whether the use of antibiotics affected the efficacy of immunotherapy for lung cancer.
"After in-depth research and exploration, a very disruptive study in 2018 came to the conclusion that within 30 days before immunotherapy, patients who applied antibiotics or experienced a decrease in immunotherapy effects." Professor Zhang Xin said.
In 2018, a number of studies on the association between lung cancer immunotherapy and intestinal microbiota were published. One of the experiments inoculated animals with beneficial gut flora showed that immunotherapy in animals was more effective. The way in which the intestinal flora of other individuals is transplanted into the recipient is also called FMT. This experiment also largely confirms the value of the intestinal microbiota in predicting the efficacy of immunotherapy and even intervention.
Several studies have been published in top medical journals, and a study in the Nature series of journals suggests that specific gut flora has been found in patients with high adverse reactions to dual immunotherapy, which means that in the future, it may be possible to treat immunotherapy toxicity by manipulating the gut microbiota while maintaining a strong response to combination therapy.
Guan Zhongshan is well-known and takes the road of Zhongshan
This year is the 7th Zhongshan Lung Cancer Forum, what kind of new situation will the future Zhongshan Lung Cancer Forum have? Professor Zhang Xin said: "Each forum is committed to the dissemination, sharing and collision of new research, new achievements and new ideas. Since the name of the Zhongshan Lung Cancer Forum is to integrate the characteristics of Zhongshan and share the experience of Zhongshan. It is worth noting that the research we have carried out in liquid biopsy has a deep foundation, especially when the number of specimens in patients with lung cancer driving gene positive is not enough, circulating tumor DNA (ctDNA) liquid biopsy can be performed. However, the bottleneck of liquid biopsy in the field of advanced lung cancer is also obvious, that is, the sensitivity is low. In the past, we have made corresponding improvements, such as improving the efficiency of blood tests through the improvement of kits, to increase the positive rate of tests. ”
In view of the small lesions that are not easy to reach with tracheoscopy, Professor Zhang Xin expressed his personal views and expectations: "In addition to obtaining biopsy tissue, consideration can be given to the application of flushing solution, followed by a series of methylation and drive gene detection, as a supplement to differential diagnosis and individualized markers." It is hoped that this new liquid biopsy may also provide a new option for patients without a confirmed diagnosis of histopathology. ”
Expert Profiles
Professor Zhang Xin
Chief Physician, M.D
Deputy Director of the Department of Respiratory Medicine, Zhongshan Hospital, Fudan University
Director of the Department of Lung Tumor and Respiratory Interventions
Member of the Interventional Science Group of the Respiratory Branch of the Chinese Medical Association
Member of the Standing Committee of the Lung Tumor Committee of the China Medical Education Association
Standing Director of the Asia-Pacific Society of Medical Bioimmunology
Vice Chairman of respiratory tumor intervention committee of Shanghai Anti-Cancer Association
Vice Chairman of the Lung Cancer Molecular Targeting and Immunotherapy Committee of Shanghai Anti-Cancer Association
Member of the editorial board of Shanghai Pharmaceutical Magazine
He has been engaged in respiratory and lung cancer diagnosis and treatment for 29 years, and has successively engaged in research work such as lung cancer gene diagnosis and gene therapy, combined application of targeted and chemotherapy, lung cancer liquid biopsy, magnetic navigation guided lung biopsy, etc., and participated in a number of international clinical trials as a sub-center PI. He has edited 6 monographs such as "Practical Internal Medicine" and published more than 30 papers.
This article was first published: Medical Oncology Channel
Author: Vigorous
Reporting expert: Zhang Xin, Zhongshan Hospital Affiliated to Fudan University
Editor-in-Charge: Sweet
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