Limits...
An Evidence-Based Review of Alternating Electric Fields Therapy for Malignant Gliomas.

Wong ET, Lok E, Swanson KD - Curr Treat Options Oncol (2015)

Bottom Line: Glioblastoma is a deadly disease and even aggressive neurosurgical resection followed by radiation and chemotherapy only extends patient survival to a median of 1.5 years.The challenge in treating this type of tumor stems from the rapid proliferation of the malignant glioma cells, the diffuse infiltrative nature of the disease, multiple activated signal transduction pathways within the tumor, development of resistant clones during treatment, the blood brain barrier that limits the delivery of drugs into the central nervous system, and the sensitivity of the brain to treatment effect.Recently, alternating electric fields, also known as tumor treating fields (TTFields), have been developed for the treatment of glioblastoma.

View Article: PubMed Central - PubMed

Affiliation: Brain Tumor Center and Neuro-Oncology Unit, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA, 02215, USA, ewong@bidmc.harvard.edu.

ABSTRACT

Opinion statement: Glioblastoma is a deadly disease and even aggressive neurosurgical resection followed by radiation and chemotherapy only extends patient survival to a median of 1.5 years. The challenge in treating this type of tumor stems from the rapid proliferation of the malignant glioma cells, the diffuse infiltrative nature of the disease, multiple activated signal transduction pathways within the tumor, development of resistant clones during treatment, the blood brain barrier that limits the delivery of drugs into the central nervous system, and the sensitivity of the brain to treatment effect. Therefore, new therapies that possess a unique mechanism of action are needed to treat this tumor. Recently, alternating electric fields, also known as tumor treating fields (TTFields), have been developed for the treatment of glioblastoma. TTFields use electromagnetic energy at an intermediate frequency of 200 kHz as a locoregional intervention and act to disrupt tumor cells as they undergo mitosis. In a phase III clinical trial for recurrent glioblastoma, TTFields were shown to have equivalent efficacy when compared to conventional chemotherapies, while lacking the typical side effects associated with chemotherapies. Furthermore, an interim analysis of a recent clinical trial in the upfront setting demonstrated superiority to standard of care cytotoxic chemotherapy, most likely because the subjects' tumors were at an earlier stage of clonal evolution, possessed less tumor-induced immunosuppression, or both. Therefore, it is likely that the efficacy of TTFields can be increased by combining it with other anti-cancer treatment modalities.

No MeSH data available.


Related in: MedlinePlus

A 3-dimensional render of a human head with TTFields clinically applied via electrode arrays on a glioblastoma patient whose gross tumor volume is on the right side. a Streamlines showing the magnitude of the electric field and direction of the current emanating from each electrode on the surface of the scalp. bRed arrows indicating vector field of the electric field distribution inside the brain. The intracranial electric fields are displayed in c axial and d coronal planes. e TTFields induce a force on the septin 2, 6, and 7 complex that has an extremely large dipole moment of 2711 Debyes. f This results in mitotic catastrophe and aberrant mitotic exit, leading to an increased cell surface expression of the endoplasmic reticulum chaperonin calreticulin and the secretion of HMGB1 that acts as a danger signal when release from cells, both of which are essential for immunogenic cell death.
© Copyright Policy - OpenAccess
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4491358&req=5

Fig1: A 3-dimensional render of a human head with TTFields clinically applied via electrode arrays on a glioblastoma patient whose gross tumor volume is on the right side. a Streamlines showing the magnitude of the electric field and direction of the current emanating from each electrode on the surface of the scalp. bRed arrows indicating vector field of the electric field distribution inside the brain. The intracranial electric fields are displayed in c axial and d coronal planes. e TTFields induce a force on the septin 2, 6, and 7 complex that has an extremely large dipole moment of 2711 Debyes. f This results in mitotic catastrophe and aberrant mitotic exit, leading to an increased cell surface expression of the endoplasmic reticulum chaperonin calreticulin and the secretion of HMGB1 that acts as a danger signal when release from cells, both of which are essential for immunogenic cell death.

Mentions: Using finite element analysis, 3-dimensional mapping of the electric field distribution within the brain revealed inhomogeneous distribution of the fields, with a higher field strength near the ventricular horns that is most likely a result of the high conductivity of the cerebrospinal fluid (Fig. 1).Fig. 1


An Evidence-Based Review of Alternating Electric Fields Therapy for Malignant Gliomas.

Wong ET, Lok E, Swanson KD - Curr Treat Options Oncol (2015)

A 3-dimensional render of a human head with TTFields clinically applied via electrode arrays on a glioblastoma patient whose gross tumor volume is on the right side. a Streamlines showing the magnitude of the electric field and direction of the current emanating from each electrode on the surface of the scalp. bRed arrows indicating vector field of the electric field distribution inside the brain. The intracranial electric fields are displayed in c axial and d coronal planes. e TTFields induce a force on the septin 2, 6, and 7 complex that has an extremely large dipole moment of 2711 Debyes. f This results in mitotic catastrophe and aberrant mitotic exit, leading to an increased cell surface expression of the endoplasmic reticulum chaperonin calreticulin and the secretion of HMGB1 that acts as a danger signal when release from cells, both of which are essential for immunogenic cell death.
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4491358&req=5

Fig1: A 3-dimensional render of a human head with TTFields clinically applied via electrode arrays on a glioblastoma patient whose gross tumor volume is on the right side. a Streamlines showing the magnitude of the electric field and direction of the current emanating from each electrode on the surface of the scalp. bRed arrows indicating vector field of the electric field distribution inside the brain. The intracranial electric fields are displayed in c axial and d coronal planes. e TTFields induce a force on the septin 2, 6, and 7 complex that has an extremely large dipole moment of 2711 Debyes. f This results in mitotic catastrophe and aberrant mitotic exit, leading to an increased cell surface expression of the endoplasmic reticulum chaperonin calreticulin and the secretion of HMGB1 that acts as a danger signal when release from cells, both of which are essential for immunogenic cell death.
Mentions: Using finite element analysis, 3-dimensional mapping of the electric field distribution within the brain revealed inhomogeneous distribution of the fields, with a higher field strength near the ventricular horns that is most likely a result of the high conductivity of the cerebrospinal fluid (Fig. 1).Fig. 1

Bottom Line: Glioblastoma is a deadly disease and even aggressive neurosurgical resection followed by radiation and chemotherapy only extends patient survival to a median of 1.5 years.The challenge in treating this type of tumor stems from the rapid proliferation of the malignant glioma cells, the diffuse infiltrative nature of the disease, multiple activated signal transduction pathways within the tumor, development of resistant clones during treatment, the blood brain barrier that limits the delivery of drugs into the central nervous system, and the sensitivity of the brain to treatment effect.Recently, alternating electric fields, also known as tumor treating fields (TTFields), have been developed for the treatment of glioblastoma.

View Article: PubMed Central - PubMed

Affiliation: Brain Tumor Center and Neuro-Oncology Unit, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA, 02215, USA, ewong@bidmc.harvard.edu.

ABSTRACT

Opinion statement: Glioblastoma is a deadly disease and even aggressive neurosurgical resection followed by radiation and chemotherapy only extends patient survival to a median of 1.5 years. The challenge in treating this type of tumor stems from the rapid proliferation of the malignant glioma cells, the diffuse infiltrative nature of the disease, multiple activated signal transduction pathways within the tumor, development of resistant clones during treatment, the blood brain barrier that limits the delivery of drugs into the central nervous system, and the sensitivity of the brain to treatment effect. Therefore, new therapies that possess a unique mechanism of action are needed to treat this tumor. Recently, alternating electric fields, also known as tumor treating fields (TTFields), have been developed for the treatment of glioblastoma. TTFields use electromagnetic energy at an intermediate frequency of 200 kHz as a locoregional intervention and act to disrupt tumor cells as they undergo mitosis. In a phase III clinical trial for recurrent glioblastoma, TTFields were shown to have equivalent efficacy when compared to conventional chemotherapies, while lacking the typical side effects associated with chemotherapies. Furthermore, an interim analysis of a recent clinical trial in the upfront setting demonstrated superiority to standard of care cytotoxic chemotherapy, most likely because the subjects' tumors were at an earlier stage of clonal evolution, possessed less tumor-induced immunosuppression, or both. Therefore, it is likely that the efficacy of TTFields can be increased by combining it with other anti-cancer treatment modalities.

No MeSH data available.


Related in: MedlinePlus