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*Only for medical professionals to read for reference.
In the age of immunotherapy, let's see the results and prospects of radiotherapy and immunotherapy in small cell lung cancer.
Small cell lung cancer (SCLC) is one of the common malignant tumors that seriously threaten the life and health of patients.
It can be divided into limited-stage small cell lung cancer (LS-SCLC) and extensive-stage small cell lung cancer (ES-SCLC).
At present, chemotherapy combined with radiotherapy is still the standard treatment plan for most LS-SCLC patients.
With the rapid development of immunotherapy, the IMpower133 research results were announced at the 2018 World Lung Cancer Conference, opening a new chapter in ES-SCLC treatment.
Pay attention to how radiotherapy is based on the current situation, how radiotherapy works with immunity to open up the road of optimization and so on.
The Medical Oncology Channel has the honor of inviting Professor Bi Nan, Professor Yang Lin, Professor Zhong Jia, and Professor Liu Wenyang from the Cancer Hospital of the Chinese Academy of Medical Sciences, Professor Zhuang Hongqing from Peking University Third Hospital, Professor Wang Liuchun, Professor Guan Yong, and Professor Sun Leina from Tianjin Cancer Hospital , Professor Song Yongchun from the Cancer Hospital of Tianjin Medical University, gave a comprehensive answer to the related questions of radiotherapy in the era of immunotherapy.
What is the status of radiotherapy in the age of immunotherapy? Professor Zhuang Hongqing: In the pre-immune era, many studies have confirmed that chest radiotherapy, preventive brain irradiation (PCI) or concurrent radiotherapy and chemotherapy can prolong the survival time of SCLC patients.
Therefore, the guidelines of the Chinese Society of Clinical Oncology (CSCO) included radiotherapy as a recommended program for SCLC patients, and established the status of thoracic radiotherapy and PCI in LS-SCLC and ES-SCLC patients.
After entering the new era of immunity, IMpower133 research opened a new chapter in ES-SCLC treatment.
The IMpower133 study is the first ES-SCLC first-line immunotherapy study with an overall survival (OS) of more than 1 year in 30 years.
Half of the patients survived for more than 12 months, and 1/3 patients survived for more than 18 months.In 2020, atelizumab was approved in China for combined chemotherapy for the first-line treatment of ES-SCLC.
Under the new standard of IMpower133 first-line treatment, immunotherapy combined with radiotherapy has become a current research hotspot.
A number of studies have pointed out that immune checkpoint inhibitors and radiotherapy have a synergistic effect, which can benefit more people.
Studies have also found that stereotactic radiotherapy (SBRT) combined with immunotherapy can increase tumor remission rate and delay disease progression.
Can routine use of consolidating chest radiotherapy further enhance the systemic activity of immunotherapy? Professor Bi Nan: Some studies have found that some patients with extensive-stage small cell lung cancer have benefited from OS after chest radiotherapy.
However, in clinical practice, distant metastasis is an important cause of treatment failure for extensive-stage small cell lung cancer.
There is room for further improvement in patients with small cell lung cancer using immunotherapy combined with radiotherapy.
Professor Zhuang Hongqing: There is no clear conclusion on this issue.
We look forward to further exploration.
In the age of immunotherapy, how to weigh the risks and benefits of radiotherapy? What is the clinical value of biomarkers related to radiotherapy side effects? Professor Song Yongchun: For patients with small cell lung cancer, radiotherapy is a very important treatment, but it is also necessary to pay attention to complications, such as pneumonia.
Now that we have entered the age of immunotherapy, we need to explore the risks and benefits of radiotherapy.
Professor Guan Yong: Studies have found that the pulmonary toxicity of chest radiotherapy + immunity is equivalent, and the pulmonary toxicity of PD-L1 combined with radiotherapy seems to be less than that of PD-1 combined with radiotherapy.
I personally believe that neither simultaneous application nor sequential application will affect the incidence of pneumonia.
The key is the choice of drugs on the one hand, and the choice of patients on the other.
Professor Yang Lin: There are basically no specific gene mutations in small cell lung cancer.
Small cell lung cancer is divided into four subtypes.
Regarding biomarkers, doctors need to pay more attention to the level of transcription factors, such as transcription factor and molecular typing, and different molecular classifications.
Types of immune microenvironment characteristics, etc.
, to carry out more exploration.
By comparing the pathological slices before and after treatment, the characteristics of side effects were found.
Professor Zhong Jia: Adverse immune reactions need to be explored from more angles.
Adverse immune reactions may be related to abnormalities in cytokines, inflammatory factors, and metabolic pathways.
What is the value of second-generation sequencing (NGS) in precision radiotherapy for lung cancer? Professor Song Yongchun: In the monitoring of tumor recurrence and metastasis, dynamic monitoring of circulating tumor cell DNA (ctDNA) can predict recurrence earlier than imaging.
Nowadays, consensus recommends NGS technology to detect minimal residual disease (MRD) of lung cancer.
MRD has been studied and explored in early non-small cell lung cancer (NSCLC), locally advanced NSCLC and oligometastatic NSCLC, confirming that ctDNA is a sensitive predictor.
However, the release of ctDNA in early-stage tumors is lower than that in advanced-stage tumors.
To ensure the accuracy of ctDNA detection in early- and mid-stage tumor patients and the detection rate of low-abundance mutations, my country has independently developed ultra-high sensitivity ATG-seq (Automated Triple Groom Sequencing) technology.
ATG-seq technology monitoring MRD can predict the risk of lung cancer recurrence, and it can prompt the recurrence of lung cancer earlier than the imaging studies, and help the early and mid-term radical tumor radiotherapy and chemotherapy patients to manage the whole process.
Studies have also found that immunoconsolidation therapy prolongs the benefit of patients after radical radiotherapy and chemotherapy.
Through ctDNA dynamic detection, it is helpful to screen people who need consolidation therapy after radiotherapy and chemotherapy.
Regarding the combination of radiotherapy and NGS, it is still under exploration.
The clinical application direction of radiotherapy and NGS panel in tumors is shown in the figure below: Figure 1.
The clinical application direction of radiotherapy and NGS panel in tumors.
Radiotherapy combined with immunotherapy is used in tumors.
How effective is the tumor with metastasis? Professor Liu Wenyang: I once treated a 68-year-old patient with small cell esophageal cancer with multiple lymph node metastasis.
At the beginning, the patient received etoposide + cisplatin chemotherapy (EP regimen) treatment, and then started to add it to EP chemotherapy.
Atelizumab (1200 mg, intravenous drip), CT showed partial tumor remission (PR).
Subsequently, the patient received radiotherapy combined with atelizumab (1200 mg, intravenous drip, d1/21d).
At present, the patient's neuron-specific enolase (NSE) is within the normal range, and it is planned to start sequential PD-L1 inhibitor therapy after the next review.
Professor Sun Leina: The incidence of small cell esophageal cancer is relatively low.
From the perspective of diagnosis, including the morphological criteria and the expression of endocrine markers, small cell esophageal cancer and small cell lung cancer are the same.
In terms of biological behavior, small cell esophageal cancer cases can be compared with other esophageal cancers.
Radiotherapy combined with immunotherapy can be used as a clinical treatment option for metastatic tumors.
Professor Guan Yong: Some studies have found that compared with radiotherapy alone, immunotherapy combined with stereotactic head radiotherapy can reduce intracranial recurrence and neurological-related deaths, and improve survival.
I met a 69-year-old female patient who was diagnosed with extensive-stage small cell carcinoma with multiple brain metastases after admission.
After the patient received etoposide + carboplatin chemotherapy combined with PD-1 inhibitor treatment, the primary tumor was significantly reduced, but the intracranial metastases increased and enlarged.
Therefore, brain radiotherapy was started, and the patient developed brain necrosis after radiotherapy, which improved after bevacizumab.
Immunotherapy combined with head radiotherapy is a double-edged sword.
It can not only reduce the intracranial recurrence rate and improve the survival rate, but also increase the risk of brain necrosis.
How to seek advantages and avoid harm is a problem that needs to be studied in the next step.
Professor Zhong Jia: After entering the age of immunotherapy, it broke the original treatment model.
In patients with symptomatic brain metastases, whether immunotherapy should be stopped during radiotherapy is a problem.
Professor Wang Liuchun: For patients with brain metastases at the time of initial treatment, I personally think that whole brain radiotherapy should be given.
In the follow-up at the later stage of the IMpower133 study, it was found that radiotherapy combined with immunotherapy is beneficial to the survival of patients with brain metastases.
Expert profile Professor Bi Nan, Department of Radiotherapy, Cancer Hospital, Chinese Academy of Medical Sciences, Professor Zhuang Hongqing, Department of Radiotherapy, Peking University Third Hospital, Professor Song Yongchun, Department of Radiotherapy, Tianjin Medical University Cancer Hospital, and Cyberknife Center, Professor Liu Wenyang, Professor Guan Yong, Department of Radiotherapy, Cancer Hospital, Chinese Academy of Medical Sciences PhD, Professor Yang Lin, Department of Radiotherapy, Cancer Hospital, Tianjin Medical University Professor Zhong Jia, Department of Pathology, Cancer Hospital, Chinese Academy of Medical Sciences Professor Wang Liuchun, Department of Oncology, Cancer Hospital, Chinese Academy of Medical Sciences, Professor Sun Leina, Department of Pulmonary Medicine, Tianjin Cancer Hospital, Tianjin Cancer Hospital
In the age of immunotherapy, let's see the results and prospects of radiotherapy and immunotherapy in small cell lung cancer.
Small cell lung cancer (SCLC) is one of the common malignant tumors that seriously threaten the life and health of patients.
It can be divided into limited-stage small cell lung cancer (LS-SCLC) and extensive-stage small cell lung cancer (ES-SCLC).
At present, chemotherapy combined with radiotherapy is still the standard treatment plan for most LS-SCLC patients.
With the rapid development of immunotherapy, the IMpower133 research results were announced at the 2018 World Lung Cancer Conference, opening a new chapter in ES-SCLC treatment.
Pay attention to how radiotherapy is based on the current situation, how radiotherapy works with immunity to open up the road of optimization and so on.
The Medical Oncology Channel has the honor of inviting Professor Bi Nan, Professor Yang Lin, Professor Zhong Jia, and Professor Liu Wenyang from the Cancer Hospital of the Chinese Academy of Medical Sciences, Professor Zhuang Hongqing from Peking University Third Hospital, Professor Wang Liuchun, Professor Guan Yong, and Professor Sun Leina from Tianjin Cancer Hospital , Professor Song Yongchun from the Cancer Hospital of Tianjin Medical University, gave a comprehensive answer to the related questions of radiotherapy in the era of immunotherapy.
What is the status of radiotherapy in the age of immunotherapy? Professor Zhuang Hongqing: In the pre-immune era, many studies have confirmed that chest radiotherapy, preventive brain irradiation (PCI) or concurrent radiotherapy and chemotherapy can prolong the survival time of SCLC patients.
Therefore, the guidelines of the Chinese Society of Clinical Oncology (CSCO) included radiotherapy as a recommended program for SCLC patients, and established the status of thoracic radiotherapy and PCI in LS-SCLC and ES-SCLC patients.
After entering the new era of immunity, IMpower133 research opened a new chapter in ES-SCLC treatment.
The IMpower133 study is the first ES-SCLC first-line immunotherapy study with an overall survival (OS) of more than 1 year in 30 years.
Half of the patients survived for more than 12 months, and 1/3 patients survived for more than 18 months.In 2020, atelizumab was approved in China for combined chemotherapy for the first-line treatment of ES-SCLC.
Under the new standard of IMpower133 first-line treatment, immunotherapy combined with radiotherapy has become a current research hotspot.
A number of studies have pointed out that immune checkpoint inhibitors and radiotherapy have a synergistic effect, which can benefit more people.
Studies have also found that stereotactic radiotherapy (SBRT) combined with immunotherapy can increase tumor remission rate and delay disease progression.
Can routine use of consolidating chest radiotherapy further enhance the systemic activity of immunotherapy? Professor Bi Nan: Some studies have found that some patients with extensive-stage small cell lung cancer have benefited from OS after chest radiotherapy.
However, in clinical practice, distant metastasis is an important cause of treatment failure for extensive-stage small cell lung cancer.
There is room for further improvement in patients with small cell lung cancer using immunotherapy combined with radiotherapy.
Professor Zhuang Hongqing: There is no clear conclusion on this issue.
We look forward to further exploration.
In the age of immunotherapy, how to weigh the risks and benefits of radiotherapy? What is the clinical value of biomarkers related to radiotherapy side effects? Professor Song Yongchun: For patients with small cell lung cancer, radiotherapy is a very important treatment, but it is also necessary to pay attention to complications, such as pneumonia.
Now that we have entered the age of immunotherapy, we need to explore the risks and benefits of radiotherapy.
Professor Guan Yong: Studies have found that the pulmonary toxicity of chest radiotherapy + immunity is equivalent, and the pulmonary toxicity of PD-L1 combined with radiotherapy seems to be less than that of PD-1 combined with radiotherapy.
I personally believe that neither simultaneous application nor sequential application will affect the incidence of pneumonia.
The key is the choice of drugs on the one hand, and the choice of patients on the other.
Professor Yang Lin: There are basically no specific gene mutations in small cell lung cancer.
Small cell lung cancer is divided into four subtypes.
Regarding biomarkers, doctors need to pay more attention to the level of transcription factors, such as transcription factor and molecular typing, and different molecular classifications.
Types of immune microenvironment characteristics, etc.
, to carry out more exploration.
By comparing the pathological slices before and after treatment, the characteristics of side effects were found.
Professor Zhong Jia: Adverse immune reactions need to be explored from more angles.
Adverse immune reactions may be related to abnormalities in cytokines, inflammatory factors, and metabolic pathways.
What is the value of second-generation sequencing (NGS) in precision radiotherapy for lung cancer? Professor Song Yongchun: In the monitoring of tumor recurrence and metastasis, dynamic monitoring of circulating tumor cell DNA (ctDNA) can predict recurrence earlier than imaging.
Nowadays, consensus recommends NGS technology to detect minimal residual disease (MRD) of lung cancer.
MRD has been studied and explored in early non-small cell lung cancer (NSCLC), locally advanced NSCLC and oligometastatic NSCLC, confirming that ctDNA is a sensitive predictor.
However, the release of ctDNA in early-stage tumors is lower than that in advanced-stage tumors.
To ensure the accuracy of ctDNA detection in early- and mid-stage tumor patients and the detection rate of low-abundance mutations, my country has independently developed ultra-high sensitivity ATG-seq (Automated Triple Groom Sequencing) technology.
ATG-seq technology monitoring MRD can predict the risk of lung cancer recurrence, and it can prompt the recurrence of lung cancer earlier than the imaging studies, and help the early and mid-term radical tumor radiotherapy and chemotherapy patients to manage the whole process.
Studies have also found that immunoconsolidation therapy prolongs the benefit of patients after radical radiotherapy and chemotherapy.
Through ctDNA dynamic detection, it is helpful to screen people who need consolidation therapy after radiotherapy and chemotherapy.
Regarding the combination of radiotherapy and NGS, it is still under exploration.
The clinical application direction of radiotherapy and NGS panel in tumors is shown in the figure below: Figure 1.
The clinical application direction of radiotherapy and NGS panel in tumors.
Radiotherapy combined with immunotherapy is used in tumors.
How effective is the tumor with metastasis? Professor Liu Wenyang: I once treated a 68-year-old patient with small cell esophageal cancer with multiple lymph node metastasis.
At the beginning, the patient received etoposide + cisplatin chemotherapy (EP regimen) treatment, and then started to add it to EP chemotherapy.
Atelizumab (1200 mg, intravenous drip), CT showed partial tumor remission (PR).
Subsequently, the patient received radiotherapy combined with atelizumab (1200 mg, intravenous drip, d1/21d).
At present, the patient's neuron-specific enolase (NSE) is within the normal range, and it is planned to start sequential PD-L1 inhibitor therapy after the next review.
Professor Sun Leina: The incidence of small cell esophageal cancer is relatively low.
From the perspective of diagnosis, including the morphological criteria and the expression of endocrine markers, small cell esophageal cancer and small cell lung cancer are the same.
In terms of biological behavior, small cell esophageal cancer cases can be compared with other esophageal cancers.
Radiotherapy combined with immunotherapy can be used as a clinical treatment option for metastatic tumors.
Professor Guan Yong: Some studies have found that compared with radiotherapy alone, immunotherapy combined with stereotactic head radiotherapy can reduce intracranial recurrence and neurological-related deaths, and improve survival.
I met a 69-year-old female patient who was diagnosed with extensive-stage small cell carcinoma with multiple brain metastases after admission.
After the patient received etoposide + carboplatin chemotherapy combined with PD-1 inhibitor treatment, the primary tumor was significantly reduced, but the intracranial metastases increased and enlarged.
Therefore, brain radiotherapy was started, and the patient developed brain necrosis after radiotherapy, which improved after bevacizumab.
Immunotherapy combined with head radiotherapy is a double-edged sword.
It can not only reduce the intracranial recurrence rate and improve the survival rate, but also increase the risk of brain necrosis.
How to seek advantages and avoid harm is a problem that needs to be studied in the next step.
Professor Zhong Jia: After entering the age of immunotherapy, it broke the original treatment model.
In patients with symptomatic brain metastases, whether immunotherapy should be stopped during radiotherapy is a problem.
Professor Wang Liuchun: For patients with brain metastases at the time of initial treatment, I personally think that whole brain radiotherapy should be given.
In the follow-up at the later stage of the IMpower133 study, it was found that radiotherapy combined with immunotherapy is beneficial to the survival of patients with brain metastases.
Expert profile Professor Bi Nan, Department of Radiotherapy, Cancer Hospital, Chinese Academy of Medical Sciences, Professor Zhuang Hongqing, Department of Radiotherapy, Peking University Third Hospital, Professor Song Yongchun, Department of Radiotherapy, Tianjin Medical University Cancer Hospital, and Cyberknife Center, Professor Liu Wenyang, Professor Guan Yong, Department of Radiotherapy, Cancer Hospital, Chinese Academy of Medical Sciences PhD, Professor Yang Lin, Department of Radiotherapy, Cancer Hospital, Tianjin Medical University Professor Zhong Jia, Department of Pathology, Cancer Hospital, Chinese Academy of Medical Sciences Professor Wang Liuchun, Department of Oncology, Cancer Hospital, Chinese Academy of Medical Sciences, Professor Sun Leina, Department of Pulmonary Medicine, Tianjin Cancer Hospital, Tianjin Cancer Hospital
