Tests blocking blood flow to the dura in adults with glioblastoma

Trial details

Who runs it

First Affiliated Hospital, Sun Yat-Sen University

Trial code

NCT05990556

Record updated

24 July 2024

Original description

Glioblastoma is the most common primary malignancy of the central nervous system with a very poor prognosis. Most of the immunotherapies that have made significant breakthroughs in the treatment of other tumors in recent years are unsatisfactory in the application of glioblastoma, which is mainly inseparable from the highly inhibitory immune microenvironment formed by the latter. Therefore, how to change this "immune desert" and better activate immune effector cells to play an anti-tumor effect is currently a hot spot in glioma immune research. In recent years, there has been continuous research support that the myeloid cells of the central nervous system are partly derived from the bone marrow of the skull, and there is a special channel connection between the skull and the dura mater, through which immune cells can be transported. This suggests that some of the tumor-associated macrophages recruited in the glioblastoma microenvironment may be passed through the dura mater. In previous animal experiments, we blocked the main blood supply to the dura mater by ligating the bilateral external carotid arteries of mice, cutting off the potential supply of dura mater to suppressor myeloid cells in the lesion. The results showed that after ligation of bilateral external carotid arteries, the survival period of tumor-forming mice was significantly prolonged and the prognosis was improved. The proportion of myeloid cells in the tumor microenvironment of mice decreased significantly, and the expression of tumor suppressor molecules such as arginase Arg1 decreased, indicating that the improvement of mouse prognosis was closely related to the proportion and phenotypic changes of myeloid cells after dural blood supply blockade. The meningeal lymphatic system of the human central nervous system has been shown to be an important part of the immune system, while the external carotid artery system, the main source of blood supply to the dura, carries abundant immune cells that ooze out to the dura mater through the endothelial window hole of the dural blood vessel, which is an important source of dural immune cells. In the glioblastoma immune microenvironment, the source of immune cells includes dural branches from the external carotid artery system in addition to branches of the internal carotid artery system. Therefore, for patients diagnosed with glioblastoma, this study involves embolization of the dural branch of the external carotid artery system (bilateral middle meningeal artery) to block the dural blood supply before craniotomy. At the same time, microsurgery under multimodal image navigation was used to remove the tumor. It is expected to be effective in reducing the proportion of myeloid suppressor cells in the tumor microenvironment, slowing the growth rate of residual tumor cells, and prolonging the tumor-free progression and survival of patients.Read full original descriptionShow less

Research on the Safety and Efficacy of Blocking Dural Blood Supply in Glioblastoma Patients

Glioblastoma is the most common primary malignancy of the central nervous system with a very poor prognosis. Most of the immunotherapies that have made significant breakthroughs in the treatment of other tumors in recent years are unsatisfactory in the application of glioblastoma, which is mainly inseparable from the highly inhibitory immune microenvironment formed by the latter. Therefore, how to change this "immune desert" and better activate immune effector cells to play an anti-tumor effect is currently a hot spot in glioma immune research. In recent years, there has been continuous research support that the myeloid cells of the central nervous system are partly derived from the bone marrow of the skull, and there is a special channel connection between the skull and the dura mater, through which immune cells can be transported. This suggests that some of the tumor-associated macrophages recruited in the glioblastoma microenvironment may be passed through the dura mater. In previous animal experiments, we blocked the main blood supply to the dura mater by ligating the bilateral external carotid arteries of mice, cutting off the potential supply of dura mater to suppressor myeloid cells in the lesion. The results showed that after ligation of bilateral external carotid arteries, the survival period of tumor-forming mice was significantly prolonged and the prognosis was improved. The proportion of myeloid cells in the tumor microenvironment of mice decreased significantly, and the expression of tumor suppressor molecules such as arginase Arg1 decreased, indicating that the improvement of mouse prognosis was closely related to the proportion and phenotypic changes of myeloid cells after dural blood supply blockade. The meningeal lymphatic system of the human central nervous system has been shown to be an important part of the immune system, while the external carotid artery system, the main source of blood supply to the dura, carries abundant immune cells that ooze out to the dura mater through the endothelial window hole of the dural blood vessel, which is an important source of dural immune cells. In the glioblastoma immune microenvironment, the source of immune cells includes dural branches from the external carotid artery system in addition to branches of the internal carotid artery system. Therefore, for patients diagnosed with glioblastoma, this study involves embolization of the dural branch of the external carotid artery system (bilateral middle meningeal artery) to block the dural blood supply before craniotomy. At the same time, microsurgery under multimodal image navigation was used to remove the tumor. It is expected to be effective in reducing the proportion of myeloid suppressor cells in the tumor microenvironment, slowing the growth rate of residual tumor cells, and prolonging the tumor-free progression and survival of patients.

Inclusion: Imaging or needle biopsy pathologically diagnosed as glioblastoma; Patients have not previously received radiotherapy, chemotherapy and other treatment modalities for intracranial lesions; There are no related contraindications such as neurovascular intervention and craniotomy.

Exclusion: The patient has other underlying medical conditions that affect survival time; The patient had other underlying medical conditions that affected follow-up or quality of life assessment; The patient's initial imaging diagnosis was glioblastoma, and the postoperative pathology confirmed nonglioblastoma; Patients do not have the above exclusion criteria and refuse to participate in clinical trials after informed consent.

ClinicalTrials.gov NCT05990556