Table 3.

Ongoing non-pharmacological trials related to optic pathway glioma

Object of investigation	Explanation
Non-pharmacological therapeutics
Ad-RTS-hIL-12	An inducible adenoviral (Ad) vector encoding human pro-inflammatory cytokine interleukin-12 (hIL-12) p70 transgene. This is under the transcriptional control of the RheoSwitch Therapeutic System (RTS) and can be activated by administration of the proprietary diacylhydrazine-based activator ligand veledimex. Activation and transcription of IL-12 is proposed to have immunomodulating and anti-neoplastic activities [63].
B7-H3-specific CAR T cell	Chimeric antigen receptor (CAR) T cell therapy has emerged as a potential treatment in a range of cancers. CAR T cells are synthetic molecules composed of antibody binding domains connected to T cell activating domains and co-stimulatory domains. This allows highly specific tumour antigen recognition and subsequent T cell activation. The B7-H3 antigen is a transmembrane protein that is overexpressed in a range of tumours, and so manufacture of CAR T cells targeted to B7-H3 may be effective in a range of solid cancers including glioma [64, 65].
Proton radiotherapy	There were two studies identified that relate to proton radiotherapy. Protons are high-energy subatomic particles that when accelerated can be used to deliver focussed ionising radiation to a tumour in order to damage its DNA—killing tumour cells and inhibiting growth. One study is focussed on assessing long-term neurocognitive, neuroendocrine and ototoxicity outcomes. The other is assessing the capacity of proton beam therapy to successfully avoid hippocampal irradiation in LGG.
MRI-guided laser heat ablation	MRI-guided laser ablation (MLA) is a minimally invasive laser surgery technique that involves a scalp incision and a small burr hole through which a laser probe is inserted into the centre of a brain tumour under MRI guidance. The probe delivers hyperthermic ablation to the tumour which can destroy tumour tissue and also disrupts the tumour blood–brain barrier potentially enhancing the delivery of chemotherapeutic agents [66].
Frameshift peptides	A frameshift mutation is caused by insertion of deletion of a nucleotide sequence into DNA that creates a ‘frameshift’ as it is not a multiple of 3 (the number of nucleotides in a codon). This frameshift alters the whole DNA sequence and results in an altered gene and subsequent protein product. These ‘frameshift peptides’ can act as new epitopes that are potential targets for tumour vaccines. The study NCT04212351 proposes to determine if NF1-associated LGGs have a specific frameshift peptide protein profile that could be targeted with a specific vaccine [67].
Imaging diagnostics
Fast paediatric imaging with Wave-CAIPI	Wave-CAIPI (controlled aliasing in parallel imaging) is an MRI-based technology that is faster than conventional MRI imaging. Parallel imaging works by acquiring a reduced amount of k-space data with an array of receiver coils. Research is underway to see if it can provide equivalent information to the current gold-standard MRI [68, 69].
Positron emission tomography	18F-Fluorodeoxyglucose (FDG) positron emission tomography (PET) is a nuclear imaging modality that identifies increased glucose uptake in tissues. FDG-PET can be fused with MRI to improve the identification of high-grade features in gliomas [70].
Psychological assessment
Social functioning	Children with brain tumours are at risk for a number of late psychological effects, including neurocognitive and social deficits. These can be assessed with psychological questionnaires [16].