Immunotherapy associated central nervous system complications in primary brain tumors

Mantica, Megan; Drappatz, Jan

doi:10.3389/fonc.2023.1124198

Cited by 4 publications

(2 citation statements)

References 170 publications

(142 reference statements)

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“…Neurotoxicity is not an infrequent, and potentially fatal complication. The spectrum of manifestations ranges from delirium and language dysfunction to seizures, coma, and fulminant cerebral edema [ 813 ]. Toxicity is related to the location of the tumor and may be reversible with intensive supportive care [ 814 ].…”

Section: Immunotherapiesmentioning

confidence: 99%

“…The application of immunotherapy to GB implies a substantial concern for immune-associated CNS neurologic complications. Acute neurologic complications associated with oncolytic viruses and other immunotherapy treatments can often be more directly linked to their intratumoral administration than to a secondary immune-response-related adverse event [ 813 ]. While serious immune-mediated adverse events are rare overall, sometimes it is difficult to distinguish immune-mediated adverse events from disease progression.…”

Section: Immunotherapiesmentioning

confidence: 99%

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Glioblastoma Therapy: Past, Present and Future

Obrador,

Moreno-Murciano,

Oriol-Caballo

et al. 2024

IJMS

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Glioblastoma (GB) stands out as the most prevalent and lethal form of brain cancer. Although great efforts have been made by clinicians and researchers, no significant improvement in survival has been achieved since the Stupp protocol became the standard of care (SOC) in 2005. Despite multimodality treatments, recurrence is almost universal with survival rates under 2 years after diagnosis. Here, we discuss the recent progress in our understanding of GB pathophysiology, in particular, the importance of glioma stem cells (GSCs), the tumor microenvironment conditions, and epigenetic mechanisms involved in GB growth, aggressiveness and recurrence. The discussion on therapeutic strategies first covers the SOC treatment and targeted therapies that have been shown to interfere with different signaling pathways (pRB/CDK4/RB1/P16ink4, TP53/MDM2/P14arf, PI3k/Akt-PTEN, RAS/RAF/MEK, PARP) involved in GB tumorigenesis, pathophysiology, and treatment resistance acquisition. Below, we analyze several immunotherapeutic approaches (i.e., checkpoint inhibitors, vaccines, CAR-modified NK or T cells, oncolytic virotherapy) that have been used in an attempt to enhance the immune response against GB, and thereby avoid recidivism or increase survival of GB patients. Finally, we present treatment attempts made using nanotherapies (nanometric structures having active anti-GB agents such as antibodies, chemotherapeutic/anti-angiogenic drugs or sensitizers, radionuclides, and molecules that target GB cellular receptors or open the blood–brain barrier) and non-ionizing energies (laser interstitial thermal therapy, high/low intensity focused ultrasounds, photodynamic/sonodynamic therapies and electroporation). The aim of this review is to discuss the advances and limitations of the current therapies and to present novel approaches that are under development or following clinical trials.

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Section: Immunotherapiesmentioning

confidence: 99%

Section: Immunotherapiesmentioning

confidence: 99%

Glioblastoma Therapy: Past, Present and Future

Obrador,

Moreno-Murciano,

Oriol-Caballo

et al. 2024

IJMS

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Phase I/II Design for Selecting Subgroup‐Specific Optimal Biological Doses for Prespecified Subgroups

Porter,

Murray,

Eaton

2024

Statistics in Medicine

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We propose a phase I/II trial design to support dose‐finding when the optimal biological dose (OBD) may differ in two prespecified patient subgroups. The proposed design uses a utility function to quantify efficacy‐toxicity trade‐offs, and a Bayesian model with spike and slab prior distributions for the subgroup effect on toxicity and efficacy to guide dosing and to facilitate identifying either subgroup‐specific OBDs or a common OBD depending on the resulting trial data. In a simulation study, we find the proposed design performs nearly as well as a design that ignores subgroups when the dose‐toxicity and dose‐efficacy relationships are the same in both subgroups, and nearly as well as a design with independent dose‐finding within each subgroup when these relationships differ across subgroups. In other words, the proposed adaptive design performs similarly to the design that would be chosen if investigators possessed foreknowledge about whether the dose‐toxicity and/or dose‐efficacy relationship differs across two prespecified subgroups. Thus, the proposed design may be effective for OBD selection when uncertainty exists about whether the OBD differs in two prespecified subgroups.

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