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*Only for medical professionals to read and reference Professor Liang Jun will take you to understand the latest developments in pancreatic cancer treatment
.
Pancreatic cancer is the most malignant tumor of the digestive tract, with insidious onset and rapid progress.
Most patients are at an advanced stage when they are diagnosed and lose the opportunity for surgery
.
How to improve the early diagnosis rate and optimize the treatment of advanced pancreatic cancer is currently a key clinical issue.
In view of this, we searched for pancreatic cancer related studies published in high-impact factor journals since 2021, and were fortunate to invite Liang Jun from Peking University International Hospital The professor made in-depth comments and analysis on 3 pancreatic cancer diagnosis and treatment studies published in the 2021 JAMA Oncology (impact factor: 24.
799) and GUT (impact factor: 19.
819) journals
.
Professor Liang Jun’s wonderful video 01 focuses on screening of high-risk populations and helps early diagnosis and treatment of pancreatic cancer.
A study published by GUT [1] evaluated the impact of monitoring of high-risk pancreatic cancer patients on long-term survival benefits
.
The study included 366 asymptomatic patients with a lifetime risk assessment of pancreatic ductal adenocarcinoma (PDAC) ≥10%, of which 201 were relatives of mutation-negative familial pancreatic cancer patients, and 165 were carriers of PDAC susceptible gene mutations
.
Subjects were subjected to an annual follow-up examination of endoscopy ultrasound (EUS) and magnetic resonance imaging (MRI)/magnetic resonance cholangiopancreatography (MRCP)
.
At a median follow-up of 63 months, of the 10 patients who developed PDAC, 6 were resectable pancreatic cancer, of which 3 were diagnosed early, and the remaining 4 were symptomatic metastatic interphase cancer
.
Among those who have been proven to have pancreatic cancer susceptibility gene mutations, the cumulative incidence of PDAC is 9.
3%.
Among them, those with CDKN2A gene mutations or Peutz-Jeghers syndrome are at a particularly high risk of pancreatic cancer; and those with a family history of pancreatic cancer (FPC) However, the cumulative incidence of PDAC in patients with negative gene mutations is 0
.
Compared with MRI/MRCP, endoscopic ultrasonography detected more solid lesions (100% vs 22%, p<0.
001) and fewer cystic lesions (42% vs 83%, p<0.
001)
.
Figure 1.
Cumulative incidence of pancreatic cancer in patients with different genetic risk stratification Professor Liang Jun commented that the most effective treatment for pancreatic cancer is early surgery.
However, the early diagnosis rate of pancreatic cancer in China is low, and most patients are at an advanced stage when they are diagnosed
.
Therefore, early detection, early diagnosis, and early treatment are key strategies to improve the survival (OS) of patients with pancreatic cancer
.
The research results published in the GUT journal provide theoretical support for "how to detect high-risk pancreatic cancer early
.
"
In recent years, there has been little progress in postoperative adjuvant treatment and advanced treatment of pancreatic cancer.
In the two fields of precision targeting and immunotherapy, there are currently no global, multi-center, phase III clinical studies that have confirmed that targeted and immunotherapy can significantly improve The survival and prognosis of patients with pancreatic cancer, therefore, the early detection of pancreatic cancer has more important clinical significance
.
The discovery of susceptibility genes and the correlation between Peutz-Jeghers syndrome and pancreatic cancer promotes the early diagnosis of pancreatic cancer to a higher level, helps to carry out radical surgical treatment as soon as possible, and is an important progress for patients to achieve long-term survival
.
02Ablative radiotherapy: a new direction in the treatment of inoperable pancreatic cancer.
JAMA Oncology recently published a study on the topic "The relationship between ablation radiotherapy and survival rate of patients with inoperable pancreatic cancer" [2], including 119 cases of locally advanced unresectable Patients with pancreatic cancer are given ablation radiotherapy after induction chemotherapy
.
The median follow-up after ablation radiotherapy was 18.
4 months, the patients’ median progression-free survival (PFS) and OS were 6.
3 months and 18.
2 months, respectively; the median follow-up after self-diagnosis was 24.
5 months, and the patients’ median PFS reached 13.
2 The median OS was 26.
8 months, more than 2 years; the 2-year local tumor progression rate was only 32.
8%, and the 2-year overall survival rate was 38%
.
16 patients had grade 3 adverse reactions, and the incidence of grade 4 and above adverse reactions was 0
.
The results of this study suggest that ablation radiotherapy is related to the long-term control of primary tumors, and good survival results can be obtained
.
Figure 2.
OS of patients undergoing ablation treatment Professor Liang Jun commented on clinical studies that compared with chemotherapy, conventional radiotherapy did not significantly improve the patient's OS, and less than 20% of patients who received conventional radiotherapy survived for 2 years or more
.
There have been precedents for the application of radiofrequency ablation in pancreatic cancer, and there are many related clinical studies.
However, due to the influence of various reasons, the application of ablation therapy in pancreatic cancer has not been clear
.
The research published by JAMA Oncology has a very high quality level, both from the point of view of evidence-based medicine and from the point of view of data.
It opens up a good treatment situation for the application of ablation therapy in the field of pancreatic cancer
.
For patients with unresectable pancreatic cancer, ablation radiotherapy can prolong the survival time of the patients, greatly alleviate the symptoms of the patients, and provide new ideas and options for clinical treatment
.
However, whether ablation radiotherapy can be widely promoted in the clinic and whether it can be written into the guideline needs further research and verification
.
03 Gut microbes and pancreatic cancer, a study in the GUT journal is worthy of further exploration in the future [3] reported the epidemiological characteristics of the internal bacterial DNA of pancreatic exocrine tumors to clarify the composition and diversity of tumor microbes, especially if it has not been Treatment and intervention of tumors
.
The researchers sequenced 18 specimens of pancreatic exocrine tumors and detected bacterial DNA in the tumors, and identified 11 completely different phyla from the sequence variation of 19 bacterial amplicons
.
Among them, the dominant flora are Proteobacteria, Bacteroides, Firmicutes and Actinomycetes, which have extensive similarities with gastrointestinal flora
.
Among them, the detection rates of γ-proteobacteria, fusobacterium, and bifidobacteria in tumors were 88%, 29%, and 12%, respectively
.
Figure 3.
Microbial distribution; the horizontal axis is the tumor specimen, the vertical axis is the name of the microorganism; the color ranges from blue (0) to dark orange (75) Professor Liang Jun commented in recent years, there have been many discussions on intestinal flora and tumors Research on the relevance of treatment, especially the relevance of targeted therapy, immunotherapy and the occurrence and change of intestinal flora
.
Preliminary studies have shown that the intestinal flora can adjust the efficacy of anticancer drugs, and the change in the intestinal flora is related to the resistance of chemotherapy drugs or immune checkpoint inhibitors; however, there is no large-scale and accurate data to confirm that the intestinal flora is related to The occurrence and development of tumors and the relevance of treatment
.
The study published in the GUT journal prospectively describes the microbial ecosystem of pancreatic exocrine tumor specimens, and provides a theoretical basis for future exploration of bacterial flora with prognostic/diagnostic value
.
Studying the process of intestinal flora and tumor occurrence and development, as well as the evaluation of therapeutic effects, drug resistance issues, and the relationship between targeted immunotherapy drugs are very good research directions in the future
.
In terms of specific pancreatic cancer, the change of intestinal flora is closely related to the occurrence and development of pancreatic cancer.
It is a very good research direction.
I believe that with the progress of research, the intestinal flora is related to the occurrence, development and resistance of pancreatic cancer.
The internal relationship of the drug problem will be more clear, and we look forward to further and in-depth research to guide clinical work
.
04 Second-line treatment of metastatic pancreatic cancer, where to go in the future Professor Liang Jun said that so far there are still few treatment options for pancreatic cancer.
The first-line treatment of advanced pancreatic cancer is mainly gemcitabine-based chemotherapy, but the overall effect is not good
.
After the failure of the first-line treatment, the second-line treatment is more difficult.
The OS benefit of albumin paclitaxel and S-1 compared with gemcitabine remains to be seen.
At this stage, the fierce targeting and immunotherapy in the oncology field have not significantly improved the pancreatic cancer.
Prognosis
.
There is an urgent need to develop second-line therapeutic drugs with better curative effects and carry out research and exploration to bring better treatment weapons and better treatment effects to clinicians and patients
.
The NAPOLI-1 study showed that the median progression-free survival (3.
1 vs 1.
5 months) of patients with metastatic pancreatic cancer who had failed gemcitabine-based chemotherapy regimens treated with irinotecan liposome + 5-FU/LV The overall survival (6.
1 vs 4.
2 months) was significantly improved
.
Subgroup analysis of the Asian population showed that the survival benefit of the Asian population was more obvious than that of the overall population.
The median OS of the irinotecan liposome + 5-FU/LV group was 5.
2 months longer than that of the 5-FU/LV group (8.
9 months vs.
3.
7 months; HR=0.
51, P=0.
025), the median PFS was extended by 2.
6 months (4.
0 months vs 1.
4 months, HR=0.
48, P=0.
011) [4]
.
The NAPOLI-1 study provides clinicians with an effective and safe new program, and also brings new hope for the second-line treatment of mPDAC patients in Asia
.
Figure 4.
Results of NAPOLI-1 study of OS in Asian population References: [1]Kasper A Overbeek, et al.
Long-term yield of pancreatic cancer surveillance in high-risk individuals.
Gut.
2021 Apr 5;gutjnl-2020-323611.
[2]Association of Ablative Radiation Therapy With Survival Among Patients With Inoperable Pancreatic Cancer.
JAMA Oncol.
2021 Mar 11;e210057.
[3]Ferga C Gleeson,et al.
Composition, diversity and potential utility of intervention-naïve pancreatic cancer intratumoral microbiome signature profiling via endoscopic ultrasound.
Gut.
2021 Mar 22;gutjnl-2021-324031.
[4]Bang YJ,Li CP,Lee KH,et al.
Liposomal irinotecan in metastatic pancreatic adenocarcinoma in Asian patients: Subgroup analysis of the NAPOLI-1 study.
Cancer Sci 2019.
Expert Profile Professor Liang Jun, Ph.
D.
Supervisor, Deputy Dean of Peking University International Hospital, Director of Cancer Center, Deputy Director of Department of Internal Medicine, Beijing Cancer Hospital, Deputy Director, Chinese Society of Clinical Oncology (CSCO), Chairman of CSCO Smart Medical Professional Committee, Deputy Director of CSCO Liver Cancer Expert Committee Member, National Health Commission, Capacity Building and Continuing Education, Oncology Expert Committee, Vice Chairman, Chinese Medical Association Oncology Branch, Vice Chairman, Medical Oncology Committee, Chinese Medical Association, Vice Chairman, Colorectal Oncology, Medical Treatment Professional Committee, Chinese Medical Doctor Association, Chinese Anti-Cancer Association, Tumor Palliative and Vice Chairman of the Committee for Rehabilitation Professionals (CRPC) Vice Chairman of the National Anti-cancer Drug Clinical Application Monitoring Management and Coordination Committee Vice Chairman of the Chinese Association of Chinese Materia Medica Cancer Drug Research Expert Committee Chairman of the National Health Commission’s Liver Cancer Expert Treatment Group Expert Group Member Servier is the French No.
The second largest pharmaceutical company, and also one of the top 30 pharmaceutical companies in the world
.
Servier is completely managed by a non-profit foundation
.
Globally, 94 million patients are treated with Servier's drugs every day
.
Servier focuses on the development of the oncology field.
A quarter of its sales are used for research and development, and 37% of it is invested in oncology, hoping to benefit more cancer patients
.
There are currently 26 anti-tumor drugs under research, including immunotherapy, targeted therapy and chemotherapy drugs, covering solid tumors and hematological tumors
.
.
Pancreatic cancer is the most malignant tumor of the digestive tract, with insidious onset and rapid progress.
Most patients are at an advanced stage when they are diagnosed and lose the opportunity for surgery
.
How to improve the early diagnosis rate and optimize the treatment of advanced pancreatic cancer is currently a key clinical issue.
In view of this, we searched for pancreatic cancer related studies published in high-impact factor journals since 2021, and were fortunate to invite Liang Jun from Peking University International Hospital The professor made in-depth comments and analysis on 3 pancreatic cancer diagnosis and treatment studies published in the 2021 JAMA Oncology (impact factor: 24.
799) and GUT (impact factor: 19.
819) journals
.
Professor Liang Jun’s wonderful video 01 focuses on screening of high-risk populations and helps early diagnosis and treatment of pancreatic cancer.
A study published by GUT [1] evaluated the impact of monitoring of high-risk pancreatic cancer patients on long-term survival benefits
.
The study included 366 asymptomatic patients with a lifetime risk assessment of pancreatic ductal adenocarcinoma (PDAC) ≥10%, of which 201 were relatives of mutation-negative familial pancreatic cancer patients, and 165 were carriers of PDAC susceptible gene mutations
.
Subjects were subjected to an annual follow-up examination of endoscopy ultrasound (EUS) and magnetic resonance imaging (MRI)/magnetic resonance cholangiopancreatography (MRCP)
.
At a median follow-up of 63 months, of the 10 patients who developed PDAC, 6 were resectable pancreatic cancer, of which 3 were diagnosed early, and the remaining 4 were symptomatic metastatic interphase cancer
.
Among those who have been proven to have pancreatic cancer susceptibility gene mutations, the cumulative incidence of PDAC is 9.
3%.
Among them, those with CDKN2A gene mutations or Peutz-Jeghers syndrome are at a particularly high risk of pancreatic cancer; and those with a family history of pancreatic cancer (FPC) However, the cumulative incidence of PDAC in patients with negative gene mutations is 0
.
Compared with MRI/MRCP, endoscopic ultrasonography detected more solid lesions (100% vs 22%, p<0.
001) and fewer cystic lesions (42% vs 83%, p<0.
001)
.
Figure 1.
Cumulative incidence of pancreatic cancer in patients with different genetic risk stratification Professor Liang Jun commented that the most effective treatment for pancreatic cancer is early surgery.
However, the early diagnosis rate of pancreatic cancer in China is low, and most patients are at an advanced stage when they are diagnosed
.
Therefore, early detection, early diagnosis, and early treatment are key strategies to improve the survival (OS) of patients with pancreatic cancer
.
The research results published in the GUT journal provide theoretical support for "how to detect high-risk pancreatic cancer early
.
"
In recent years, there has been little progress in postoperative adjuvant treatment and advanced treatment of pancreatic cancer.
In the two fields of precision targeting and immunotherapy, there are currently no global, multi-center, phase III clinical studies that have confirmed that targeted and immunotherapy can significantly improve The survival and prognosis of patients with pancreatic cancer, therefore, the early detection of pancreatic cancer has more important clinical significance
.
The discovery of susceptibility genes and the correlation between Peutz-Jeghers syndrome and pancreatic cancer promotes the early diagnosis of pancreatic cancer to a higher level, helps to carry out radical surgical treatment as soon as possible, and is an important progress for patients to achieve long-term survival
.
02Ablative radiotherapy: a new direction in the treatment of inoperable pancreatic cancer.
JAMA Oncology recently published a study on the topic "The relationship between ablation radiotherapy and survival rate of patients with inoperable pancreatic cancer" [2], including 119 cases of locally advanced unresectable Patients with pancreatic cancer are given ablation radiotherapy after induction chemotherapy
.
The median follow-up after ablation radiotherapy was 18.
4 months, the patients’ median progression-free survival (PFS) and OS were 6.
3 months and 18.
2 months, respectively; the median follow-up after self-diagnosis was 24.
5 months, and the patients’ median PFS reached 13.
2 The median OS was 26.
8 months, more than 2 years; the 2-year local tumor progression rate was only 32.
8%, and the 2-year overall survival rate was 38%
.
16 patients had grade 3 adverse reactions, and the incidence of grade 4 and above adverse reactions was 0
.
The results of this study suggest that ablation radiotherapy is related to the long-term control of primary tumors, and good survival results can be obtained
.
Figure 2.
OS of patients undergoing ablation treatment Professor Liang Jun commented on clinical studies that compared with chemotherapy, conventional radiotherapy did not significantly improve the patient's OS, and less than 20% of patients who received conventional radiotherapy survived for 2 years or more
.
There have been precedents for the application of radiofrequency ablation in pancreatic cancer, and there are many related clinical studies.
However, due to the influence of various reasons, the application of ablation therapy in pancreatic cancer has not been clear
.
The research published by JAMA Oncology has a very high quality level, both from the point of view of evidence-based medicine and from the point of view of data.
It opens up a good treatment situation for the application of ablation therapy in the field of pancreatic cancer
.
For patients with unresectable pancreatic cancer, ablation radiotherapy can prolong the survival time of the patients, greatly alleviate the symptoms of the patients, and provide new ideas and options for clinical treatment
.
However, whether ablation radiotherapy can be widely promoted in the clinic and whether it can be written into the guideline needs further research and verification
.
03 Gut microbes and pancreatic cancer, a study in the GUT journal is worthy of further exploration in the future [3] reported the epidemiological characteristics of the internal bacterial DNA of pancreatic exocrine tumors to clarify the composition and diversity of tumor microbes, especially if it has not been Treatment and intervention of tumors
.
The researchers sequenced 18 specimens of pancreatic exocrine tumors and detected bacterial DNA in the tumors, and identified 11 completely different phyla from the sequence variation of 19 bacterial amplicons
.
Among them, the dominant flora are Proteobacteria, Bacteroides, Firmicutes and Actinomycetes, which have extensive similarities with gastrointestinal flora
.
Among them, the detection rates of γ-proteobacteria, fusobacterium, and bifidobacteria in tumors were 88%, 29%, and 12%, respectively
.
Figure 3.
Microbial distribution; the horizontal axis is the tumor specimen, the vertical axis is the name of the microorganism; the color ranges from blue (0) to dark orange (75) Professor Liang Jun commented in recent years, there have been many discussions on intestinal flora and tumors Research on the relevance of treatment, especially the relevance of targeted therapy, immunotherapy and the occurrence and change of intestinal flora
.
Preliminary studies have shown that the intestinal flora can adjust the efficacy of anticancer drugs, and the change in the intestinal flora is related to the resistance of chemotherapy drugs or immune checkpoint inhibitors; however, there is no large-scale and accurate data to confirm that the intestinal flora is related to The occurrence and development of tumors and the relevance of treatment
.
The study published in the GUT journal prospectively describes the microbial ecosystem of pancreatic exocrine tumor specimens, and provides a theoretical basis for future exploration of bacterial flora with prognostic/diagnostic value
.
Studying the process of intestinal flora and tumor occurrence and development, as well as the evaluation of therapeutic effects, drug resistance issues, and the relationship between targeted immunotherapy drugs are very good research directions in the future
.
In terms of specific pancreatic cancer, the change of intestinal flora is closely related to the occurrence and development of pancreatic cancer.
It is a very good research direction.
I believe that with the progress of research, the intestinal flora is related to the occurrence, development and resistance of pancreatic cancer.
The internal relationship of the drug problem will be more clear, and we look forward to further and in-depth research to guide clinical work
.
04 Second-line treatment of metastatic pancreatic cancer, where to go in the future Professor Liang Jun said that so far there are still few treatment options for pancreatic cancer.
The first-line treatment of advanced pancreatic cancer is mainly gemcitabine-based chemotherapy, but the overall effect is not good
.
After the failure of the first-line treatment, the second-line treatment is more difficult.
The OS benefit of albumin paclitaxel and S-1 compared with gemcitabine remains to be seen.
At this stage, the fierce targeting and immunotherapy in the oncology field have not significantly improved the pancreatic cancer.
Prognosis
.
There is an urgent need to develop second-line therapeutic drugs with better curative effects and carry out research and exploration to bring better treatment weapons and better treatment effects to clinicians and patients
.
The NAPOLI-1 study showed that the median progression-free survival (3.
1 vs 1.
5 months) of patients with metastatic pancreatic cancer who had failed gemcitabine-based chemotherapy regimens treated with irinotecan liposome + 5-FU/LV The overall survival (6.
1 vs 4.
2 months) was significantly improved
.
Subgroup analysis of the Asian population showed that the survival benefit of the Asian population was more obvious than that of the overall population.
The median OS of the irinotecan liposome + 5-FU/LV group was 5.
2 months longer than that of the 5-FU/LV group (8.
9 months vs.
3.
7 months; HR=0.
51, P=0.
025), the median PFS was extended by 2.
6 months (4.
0 months vs 1.
4 months, HR=0.
48, P=0.
011) [4]
.
The NAPOLI-1 study provides clinicians with an effective and safe new program, and also brings new hope for the second-line treatment of mPDAC patients in Asia
.
Figure 4.
Results of NAPOLI-1 study of OS in Asian population References: [1]Kasper A Overbeek, et al.
Long-term yield of pancreatic cancer surveillance in high-risk individuals.
Gut.
2021 Apr 5;gutjnl-2020-323611.
[2]Association of Ablative Radiation Therapy With Survival Among Patients With Inoperable Pancreatic Cancer.
JAMA Oncol.
2021 Mar 11;e210057.
[3]Ferga C Gleeson,et al.
Composition, diversity and potential utility of intervention-naïve pancreatic cancer intratumoral microbiome signature profiling via endoscopic ultrasound.
Gut.
2021 Mar 22;gutjnl-2021-324031.
[4]Bang YJ,Li CP,Lee KH,et al.
Liposomal irinotecan in metastatic pancreatic adenocarcinoma in Asian patients: Subgroup analysis of the NAPOLI-1 study.
Cancer Sci 2019.
Expert Profile Professor Liang Jun, Ph.
D.
Supervisor, Deputy Dean of Peking University International Hospital, Director of Cancer Center, Deputy Director of Department of Internal Medicine, Beijing Cancer Hospital, Deputy Director, Chinese Society of Clinical Oncology (CSCO), Chairman of CSCO Smart Medical Professional Committee, Deputy Director of CSCO Liver Cancer Expert Committee Member, National Health Commission, Capacity Building and Continuing Education, Oncology Expert Committee, Vice Chairman, Chinese Medical Association Oncology Branch, Vice Chairman, Medical Oncology Committee, Chinese Medical Association, Vice Chairman, Colorectal Oncology, Medical Treatment Professional Committee, Chinese Medical Doctor Association, Chinese Anti-Cancer Association, Tumor Palliative and Vice Chairman of the Committee for Rehabilitation Professionals (CRPC) Vice Chairman of the National Anti-cancer Drug Clinical Application Monitoring Management and Coordination Committee Vice Chairman of the Chinese Association of Chinese Materia Medica Cancer Drug Research Expert Committee Chairman of the National Health Commission’s Liver Cancer Expert Treatment Group Expert Group Member Servier is the French No.
The second largest pharmaceutical company, and also one of the top 30 pharmaceutical companies in the world
.
Servier is completely managed by a non-profit foundation
.
Globally, 94 million patients are treated with Servier's drugs every day
.
Servier focuses on the development of the oncology field.
A quarter of its sales are used for research and development, and 37% of it is invested in oncology, hoping to benefit more cancer patients
.
There are currently 26 anti-tumor drugs under research, including immunotherapy, targeted therapy and chemotherapy drugs, covering solid tumors and hematological tumors
.
