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Most recent update of preclinical and clinical data on radioresistance and radiosensitivity of high-grade gliomas—a radiation oncologist’s perspective

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Abstract

Purpose

This review article discusses the studies concerning advances in radiotherapy of high-grade gliomas published in the second half of 2021.

Methods

A literature search was performed in PubMed using the terms (“gliom* and radio*”) and time limits 1 July 2021–31 December 2021. The articles were then manually selected for relevance to the analyzed topics.

Results

Considerable progress has been made in the preclinical field on the mechanisms of radioresistance and radiosensitization of high-grade gliomas (HGG). However, fewer early-phase (I/II) clinical trials have been performed and, of the latter, even fewer have produced results that justify moving to phase III. In the 6‑month period under consideration, no studies were published that would lead to a change in clinical practice and the overall survival (OS) of patients remained similar to that of 2005, the year in which it increased significantly for the last time thanks to introduction of the alkylating agent temozolomide.

Conclusion

After 17 years of stalemate in improving the OS of patients with HGG, an in-depth analysis of the causes should be carried out in order to identify whether the research efforts conducted so far, including in the radiotherapeutic field, have been the most effective or require improvement. In our opinion, in addition to the therapeutic difficulties related to the biology of HGG tumors (e.g., high infiltrating capacity, multiple resistance mechanisms, blood–brain barrier), some public research policy choices may also play a role, especially in consideration of the limited interest of the pharmaceutical industry in the field of rare cancers.

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Abbreviations

2‑HG:

2‑Hydroxyglutarate

4‑IPP:

4‑Iodo-6-phenylpyrimidine

ACER3:

Alkaline ceramidase 3

ATR:

Ataxia telangiectasia and RAD3 related

ATRX:

X‑linked locus of alpha thalassemia/mental retardation syndrome

BBB:

Blood–brain barrier

CAT:

Catalase

CCL5:

Chemokine ligand 5

CCNU:

Lomustine

CCR5:

Chemokine receptor 5

CENPB:

Centromere protein B

CHT:

Chemotherapy

CI:

Confidence interval

circHIPK3:

Circular RNA homeodomain interacting protein kinase 3

circRNA:

Circular RNA

CTV:

Clinical target volume

DCE-MRI:

Dynamic contrast-enhanced MRI

DDT:

D‑dopachrome tautomerase

DIPG:

Diffuse intrinsic pontine glioma

DMG:

Diffuse midline glioma

FAZA:

Fluoroazomycin arabinoside

FBXW7:

F‑box and WD repeat domain-containing 7

GARD:

Genome-adjusted radiation dose

GB:

Glioblastoma

GIC:

Glioma-initiating cell

GKRS:

Gamma Knife radiosurgery

HDAC:

Histone deacetylase

HFSRT:

Hypofractionated stereotactic RT

HGF:

Hepatocyte growth factor

HGG:

High-grade glioma

HIF:

Hypoxia-inducible factor

HR:

Hazard ratio

HRS:

Hyper-radiosensitivity

IDH:

Isocitrate dehydrogenase

IR:

Ionizing radiation

iRT:

Intermittent RT

Ktrans:

Volume transfer constant

LDFRT:

Low-dose fractionated RT

LGMN:

Legumain

Lnc RNA:

Long noncoding RNA

MGMT:

O‑6-methylguanine DNA methyltransferase

MIF:

Migration inhibitory factor

miR:

MicroRNA

MRI:

Magnetic resonance imaging

ncRNA:

Non-coding RNA

NRF:

Erythroid-related nuclear factor

NSG:

NOD scid gamma

NTRK:

Neurotrophic tyrosine receptor kinase

OS:

Overall survival

PARP:

Poly (ADP-ribose) polymerase

PDX:

Patient-derived xenograft

PFS:

Progression-free survival

ROS:

Reactive oxygen species

RT:

Radiotherapy

rRT:

Re-irradiation

SASP:

Senescence-associated secretory phenotype

SFRP2:

Secreted frizzled-related protein 2

STAT3:

Signal transducer and activator of transcription 3

TCGA:

The Cancer Genome Atlas

TMZ:

Temozolomide

TRAP1:

TNF receptor-associated protein 1

TTFields:

Tumor-treating fields

TWEAK/Fn14:

TNF-like weak inducer of apoptosis/fibroblast growth factor-inducible 14

UCSC:

University of California Santa Cruz

Ultra-hyper-FRT:

Ultrahyperfractionated RT

Ve:

Extravascular extracellular volume fraction

VEGF:

Vascular endothelial growth factor

WHO:

World Health Organization

YAP:

Yes-associated protein

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  1. Mutagenesis & Cancer Prevention Unit, IRCCS Ospedale Policlinico San Martino, Largo Rosanna Benzi 10, 16132, Genova, Italy

    Guido Frosina

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Frosina, G. Most recent update of preclinical and clinical data on radioresistance and radiosensitivity of high-grade gliomas—a radiation oncologist’s perspective. Strahlenther Onkol 199, 1–21 (2023). https://doi.org/10.1007/s00066-022-02020-2

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