The prognosis of brain metastases(BM)is traditionally poor.BM are mainly treated by local radiotherapy,including stereotactic radiosurgery(SRS)or whole brain radiation therapy(WBRT).Recently,immunotherapy(i.e.,immune ...The prognosis of brain metastases(BM)is traditionally poor.BM are mainly treated by local radiotherapy,including stereotactic radiosurgery(SRS)or whole brain radiation therapy(WBRT).Recently,immunotherapy(i.e.,immune checkpoint inhibitors,ICI)has demonstrated a survival advantage in multiple malignancies commonly associated with BM.Individually,radiotherapy and ICI both treat BM efficiently;hence,their combination seems logical.In this review,we summarize the existing preclinical and clinical evidence that supports the applicability of radiotherapy as a sensitizer of ICI for BM.Further,we discuss the optimal timing at which radiotherapy and ICI should be administered and review the safety of the combination therapy.Data from a few clinical studies suggest that combining SRS or WBRT with ICI simultaneously rather than consecutively potentially enhances brain abscopal-like responses and survival.However,there is a lack of conclusion about the definition of"simultaneous";the cumulative toxic effect of the combined therapies also requires further study.Thus,ongoing and planned prospective trials are needed to further explore and validate the effect,safety,and optimal timing of the combination of immunotherapy with radiotherapy for patients with BM.展开更多
BACKGROUND Melanoma brain metastasis is a common cause of death in melanoma patients andis associated with a poor prognosis. There are relatively few reports onintracranial infections after brain metastasis resection....BACKGROUND Melanoma brain metastasis is a common cause of death in melanoma patients andis associated with a poor prognosis. There are relatively few reports onintracranial infections after brain metastasis resection.CASE SUMMARY Here we report a case of melanoma brain metastases in a patient harboring aBRAF V600E mutation, who experienced intracranial tumor progression despiteprevious combined treatment with a programmed death (PD)-1 inhibitor, axitinib,and vemurafenib. She repeatedly underwent local therapy, including stereotacticradiosurgery and intracranial surgery, and developed central nervous systeminfection. Treatment with vemurafenib combined with cobimetinib resulted in anintracranial progression-free survival of 10 mo. During the coronavirus disease2019 (COVID-19) pandemic, the patient did not visit the hospital for regularvemurafenib treatment, and experienced intracranial progression afterinvoluntary drug reduction for 1 mo. The patient subsequently received varioussystemic treatments including vemurafenib, PD-1 inhibitor, and chemotherapy,with an overall survival of 29 mo as of September 2020.CONCLUSION We report the first case of melanoma brain metastases with co-occurringintracranial infection and unintended drug reduction during the COVID-19outbreak. Long-term control of the intracranial lesions was achieved withsystemic and local therapies.展开更多
This report gives a better emphasis on the role of targeted effectors (e.g. a combination of 5-FC with CD-NSPCs as compared to the application of NSPCs alone) and how such delivery of pro-drug activating enzymes and o...This report gives a better emphasis on the role of targeted effectors (e.g. a combination of 5-FC with CD-NSPCs as compared to the application of NSPCs alone) and how such delivery of pro-drug activating enzymes and other tumor-killing substances may overcome melanocytic defence system, interact with and promote the host defence and immune response modulations not only in melanoma but, potentially, in other highly-metastatic cancers.展开更多
Brain metastases are the most common central nervous system malignancies in adults.The popular view is that due to the existence of the blood–brain barrier,whether there are immune cells in the central nervous system...Brain metastases are the most common central nervous system malignancies in adults.The popular view is that due to the existence of the blood–brain barrier,whether there are immune cells in the central nervous system has always been controversial.Current research shows that immune cells do exist in the central nervous system and play a vital role in the occurrence and development of brain metastasis.The central nervous system has a unique immune microenvironment,and the study of its mechanism is of great significance for the prediction and treatment of brain metastases.This article aims to discuss the components of the brain tumor microenvironment(TME)and immune mechanism of tumor brain metastasis,in the hopes of making better treatment through combination therapy.展开更多
Brain metastases are significant causes of morbidity or mortality for patients with metastatic cancer.With the application of novel systematic therapy and improvement of overall survival,the prevalence of brain metast...Brain metastases are significant causes of morbidity or mortality for patients with metastatic cancer.With the application of novel systematic therapy and improvement of overall survival,the prevalence of brain metastases is increasing.The paradigm of treatment for brain metastases evolved rapidly during the last 30 years due to the development of technology and emergence of novel therapy.Brain metastases used to be regarded as the terminal stage of cancer and left life expectancy to only 1 month.The application of whole brain radiotherapy for patients with brain metastases increased the life expectancy to 4–6 months in the 1980s.Following studies established surgical resection followed by the application of whole brain radiotherapy the standard treatment for patients with single metastasis and good systematic performance.With the development of stereotactic radiosurgery,stereotactic radiosurgery plus whole brain radiotherapy provides an alternative modality with superior neurocognitive protection at the cost of overall survival.In addition,stereotactic radiosurgery combined with whole brain radiotherapy may offer a promising modality for patients with numerous multiple brain metastases who are not eligible for surgical resection.With the advancing understanding of molecular pathway and biological behavior of oncogenesis and tumor metastasis,novel targeted therapy including tyrosine-kinase inhibitors and immunotherapy are applied to brain metastases.Clinical trials had revealed the efficacy of targeted therapy.Furthermore,the combination of targeted therapy and radiotherapy or chemotherapy is the highlight of current investigation.Advancement in this area may further change the treatment paradigm and offer better modality for patients who are not suitable for surgical resection or radiosurgery.展开更多
脑转移瘤是成人恶性神经系统肿瘤最常见的病因。针对这一部分人群,治疗手段有限,预后不佳。近年来,以程序性死亡受体1(programmed cell death protein 1,PD-1)及程序性死亡受体配体1(programmed cell death protein ligand 1,PD-L1)抑...脑转移瘤是成人恶性神经系统肿瘤最常见的病因。针对这一部分人群,治疗手段有限,预后不佳。近年来,以程序性死亡受体1(programmed cell death protein 1,PD-1)及程序性死亡受体配体1(programmed cell death protein ligand 1,PD-L1)抑制剂为主的免疫治疗,给恶性肿瘤的治疗模式带来了革新。免疫检查点抑制剂(immune checkpoint inhibitors,ICIs)彻底改变了晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)的治疗模式。ICI在某些驱动基因阴性的NSCLC脑转移瘤治疗中,取得了令人鼓舞的结果。然而,针对脑转移瘤患者的临床研究,不仅相应的临床数据有限,其疗效的评价也缺乏统一标准。本文旨在阐述不同的疗效评价标准及其在临床研究中的应用,比较之间的异同,并对未来发展趋势进行展望。展开更多
基金This work was supported by National Key Research and Development Program of China(No.2O18YFC1311400,2O18YFC1311402)National Natural Science Foundation of China(No.81672982,81872478).
文摘The prognosis of brain metastases(BM)is traditionally poor.BM are mainly treated by local radiotherapy,including stereotactic radiosurgery(SRS)or whole brain radiation therapy(WBRT).Recently,immunotherapy(i.e.,immune checkpoint inhibitors,ICI)has demonstrated a survival advantage in multiple malignancies commonly associated with BM.Individually,radiotherapy and ICI both treat BM efficiently;hence,their combination seems logical.In this review,we summarize the existing preclinical and clinical evidence that supports the applicability of radiotherapy as a sensitizer of ICI for BM.Further,we discuss the optimal timing at which radiotherapy and ICI should be administered and review the safety of the combination therapy.Data from a few clinical studies suggest that combining SRS or WBRT with ICI simultaneously rather than consecutively potentially enhances brain abscopal-like responses and survival.However,there is a lack of conclusion about the definition of"simultaneous";the cumulative toxic effect of the combined therapies also requires further study.Thus,ongoing and planned prospective trials are needed to further explore and validate the effect,safety,and optimal timing of the combination of immunotherapy with radiotherapy for patients with BM.
基金Beijing Municipal Administration of Hospitals’Youth Programme,No.QML20181101Beijing Municipal Administration of Hospitals Incubating Program,No.PX2017042.
文摘BACKGROUND Melanoma brain metastasis is a common cause of death in melanoma patients andis associated with a poor prognosis. There are relatively few reports onintracranial infections after brain metastasis resection.CASE SUMMARY Here we report a case of melanoma brain metastases in a patient harboring aBRAF V600E mutation, who experienced intracranial tumor progression despiteprevious combined treatment with a programmed death (PD)-1 inhibitor, axitinib,and vemurafenib. She repeatedly underwent local therapy, including stereotacticradiosurgery and intracranial surgery, and developed central nervous systeminfection. Treatment with vemurafenib combined with cobimetinib resulted in anintracranial progression-free survival of 10 mo. During the coronavirus disease2019 (COVID-19) pandemic, the patient did not visit the hospital for regularvemurafenib treatment, and experienced intracranial progression afterinvoluntary drug reduction for 1 mo. The patient subsequently received varioussystemic treatments including vemurafenib, PD-1 inhibitor, and chemotherapy,with an overall survival of 29 mo as of September 2020.CONCLUSION We report the first case of melanoma brain metastases with co-occurringintracranial infection and unintended drug reduction during the COVID-19outbreak. Long-term control of the intracranial lesions was achieved withsystemic and local therapies.
文摘This report gives a better emphasis on the role of targeted effectors (e.g. a combination of 5-FC with CD-NSPCs as compared to the application of NSPCs alone) and how such delivery of pro-drug activating enzymes and other tumor-killing substances may overcome melanocytic defence system, interact with and promote the host defence and immune response modulations not only in melanoma but, potentially, in other highly-metastatic cancers.
基金supported by Jilin Scientific and Technological Development Program(CN)(20190303146SF)(Jiuwei Cui)General Program of National Natural Science Foundation of China(81874052)(Jiuwei Cui).
文摘Brain metastases are the most common central nervous system malignancies in adults.The popular view is that due to the existence of the blood–brain barrier,whether there are immune cells in the central nervous system has always been controversial.Current research shows that immune cells do exist in the central nervous system and play a vital role in the occurrence and development of brain metastasis.The central nervous system has a unique immune microenvironment,and the study of its mechanism is of great significance for the prediction and treatment of brain metastases.This article aims to discuss the components of the brain tumor microenvironment(TME)and immune mechanism of tumor brain metastasis,in the hopes of making better treatment through combination therapy.
文摘Brain metastases are significant causes of morbidity or mortality for patients with metastatic cancer.With the application of novel systematic therapy and improvement of overall survival,the prevalence of brain metastases is increasing.The paradigm of treatment for brain metastases evolved rapidly during the last 30 years due to the development of technology and emergence of novel therapy.Brain metastases used to be regarded as the terminal stage of cancer and left life expectancy to only 1 month.The application of whole brain radiotherapy for patients with brain metastases increased the life expectancy to 4–6 months in the 1980s.Following studies established surgical resection followed by the application of whole brain radiotherapy the standard treatment for patients with single metastasis and good systematic performance.With the development of stereotactic radiosurgery,stereotactic radiosurgery plus whole brain radiotherapy provides an alternative modality with superior neurocognitive protection at the cost of overall survival.In addition,stereotactic radiosurgery combined with whole brain radiotherapy may offer a promising modality for patients with numerous multiple brain metastases who are not eligible for surgical resection.With the advancing understanding of molecular pathway and biological behavior of oncogenesis and tumor metastasis,novel targeted therapy including tyrosine-kinase inhibitors and immunotherapy are applied to brain metastases.Clinical trials had revealed the efficacy of targeted therapy.Furthermore,the combination of targeted therapy and radiotherapy or chemotherapy is the highlight of current investigation.Advancement in this area may further change the treatment paradigm and offer better modality for patients who are not suitable for surgical resection or radiosurgery.
文摘脑转移瘤是成人恶性神经系统肿瘤最常见的病因。针对这一部分人群,治疗手段有限,预后不佳。近年来,以程序性死亡受体1(programmed cell death protein 1,PD-1)及程序性死亡受体配体1(programmed cell death protein ligand 1,PD-L1)抑制剂为主的免疫治疗,给恶性肿瘤的治疗模式带来了革新。免疫检查点抑制剂(immune checkpoint inhibitors,ICIs)彻底改变了晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)的治疗模式。ICI在某些驱动基因阴性的NSCLC脑转移瘤治疗中,取得了令人鼓舞的结果。然而,针对脑转移瘤患者的临床研究,不仅相应的临床数据有限,其疗效的评价也缺乏统一标准。本文旨在阐述不同的疗效评价标准及其在临床研究中的应用,比较之间的异同,并对未来发展趋势进行展望。
