HGG-22. Uptake of investigational therapy in children with High Grade Glioma

Abstract

High grade gliomas (HGG) in children carry a dismal prognosis. Standard therapy includes resection when possible, radiotherapy and sometimes the addition of temozolomide. There is no standard treatment for progression or relapse. Since November 2018 we have offered upfront molecular testing to all children with HGG who had biopsy/ resection. Testing was mainly done by next generation sequencing panel, and some had research based methylation profiling and RNA seq. We aimed to see whether families chose to receive additional investigational treatment as a result of the molecular testing results and whether the treatment involved participation in a clinical study, or whether treatment was compassionate. A total of 22 patients aged 2.8-16.8 years with HGG had a biopsy/resection over this three year period. Thirteen had diffuse midline glioma (DMG) of which 11 had the H3K27 mutation, and 9 were cortical. Six children had underlying predisposition syndromes: mismatch repair deficiency (n=3 proven + 1 highly suspected), neurofibromatosis1 (n=1), Li-Fraumeni (n=1). All the cortical gliomas had potential treatment options based on their molecular testing. 10/22 (45%) children received investigational therapy of which only three participated in a clinical study while the rest received compassionate therapy. Compassionate treatments included BRAF/MEK inhibitors (n=4), Larotrectinib (n=1), and immune checkpoint inhibitors (n=2). Of the 12 who did not receive investigational therapy, four, all cortical, have potential therapy options but are currently in remission. Of the remaining eight, two had very rapid clinical deterioration and died, and six (all DMG) did not wish/ were unable to travel abroad and no relevant clinical study was available locally. We conclude that the families of children with HGG are highly motivated to receive investigational therapy. Upfront molecular testing of these tumors, especially for cortical HGG, is imperative and there is a growing need for accessible clinical studies.

Enhancing Surface Hydroxyl Group Modulation on Carbon Nitride Boosts the Effectiveness of Photodynamic Treatment for Brain Glioma

“…1−3 Despite significant progress in clinical treatment methods, such as surgery, chemotherapy, and radiation therapy, glioma remains prone to recurrence with almost irreversible side effects. 4,5 Although great efforts have been made in recent years, there are still limitations in improving the prognosis of glioma. 6,7 With the development of nanoscience, nanomaterials and nanotechnology have been widely utilized in biology, medicine, and related fields, which have propelled the advancement of nanomedicine offering novel prospects for cancer therapy.…”

“…Glioma is the most prevalent malignant tumor of the nervous system. − Despite significant progress in clinical treatment methods, such as surgery, chemotherapy, and radiation therapy, glioma remains prone to recurrence with almost irreversible side effects. , Although great efforts have been made in recent years, there are still limitations in improving the prognosis of glioma. , With the development of nanoscience, nanomaterials and nanotechnology have been widely utilized in biology, medicine, and related fields, which have propelled the advancement of nanomedicine offering novel prospects for cancer therapy. One crucial facet of nanomedicine involves designing multifunctional drug delivery carriers using nanotechnology to develop new drug formulations and therapeutics. − Photodynamic (PDT) therapy is an indispensable technology that employs photosensitizers (PS) as PDT agents due to their localized impact on tumors with reduced adverse effects compared to conventional treatments while being minimally invasive with high spatial precision advantages making it a promising modality for treating gliomas. − Photosensitizers can effectively generate cytotoxic reactive oxygen species (ROS) directly or indirectly, inducing tumor cell death through type I or type II PDT reactions.…”