The potential of advanced MR techniques for precision radiotherapy of glioblastoma

Abstract

As microscopic tumour infiltration of glioblastomas is not visible on conventional magnetic resonance (MR) imaging, an isotropic expansion of 1–2 cm around the visible tumour is applied to define the clinical target volume for radiotherapy. An opportunity to visualize microscopic infiltration arises with advanced MR imaging. In this review, various advanced MR biomarkers are explored that could improve target volume delineation for radiotherapy of glioblastomas. Various physiological processes in glioblastomas can be visualized with different advanced MR techniques. Combining maps of oxygen metabolism (CMRO2), relative cerebral blood volume (rCBV), vessel size imaging (VSI), and apparent diffusion coefficient (ADC) or amide proton transfer (APT) can provide early information on tumour infiltration and high-risk regions of future recurrence. Oxygen consumption is increased 6 months prior to tumour progression being visible on conventional MR imaging. However, presence of the Warburg effect, marking a switch from an infiltrative to a proliferative phenotype, could result in CMRO2 to appear unaltered in high-risk regions. Including information on biomarkers representing angiogenesis (rCBV and VSI) and hypercellularity (ADC) or protein concentration (APT) can omit misinterpretation due to the Warburg effect. Future research should evaluate these biomarkers in radiotherapy planning to explore the potential of advanced MR techniques to personalize target volume delineation with the aim to improve local tumour control and/or reduce radiation-induced toxicity.

Evaluating Physiological MRI Parameters in Patients with Brain Metastases Undergoing Stereotactic Radiosurgery—A Preliminary Analysis and Case Report

“…The primary tumor (i.e., origin of metastatic cells), might cause some of this heterogeneity as it affects the brain metastases growth pattern, metabolism and vasculature [6,10,54,55]. As the CMRO 2 was not different from that of healthy-appearing tissue, this could be illustrative of the Warburg effect (i.e., less reliant on oxidative metabolism and more on aerobic glycolysis), especially since the OEF was lower than in healthy-appearing WM [56][57][58]. Moreover, we observed low OEF, CBF, CMRO 2 and CVR within the edema regions.…”

Non-targeted effects of radiation therapy for glioblastoma

“…IMRT offers additional ability of adjusting beam intensity to deliver higher doses in a shorter time [ 38 ] and IGRT to perform a precise gradient of radiation between tumor volume and adjacent healthy tissue, thanks to medical imaging techniques, allowing a precise delineation. For instance, magnetic resonance imaging (MRI) has become essential in this context [ 39 ], whereas functional imaging, using variety positron emission tomography (PET) tracers, is still under consideration [ 40 ]. VMAT is an evolution of IMRT, allowing full 360° rotation to achieve continuous radiation beams, which reduces treatment time [ 36 ].…”

Exosomal DNA: Role in Reflecting Tumor Genetic Heterogeneity, Diagnosis, and Disease Monitoring

“…While the frequency of mtDNA point mutations showed slight variations between cases and controls, the clinical implications of these findings were inconclusive. Considering that the glioblastoma was characterized as the Warburg phenotype [ 56 , 57 ], the researchers suggested that the observed mtDNA mutations and copy number changes may have contributed to the adaptation of altered metabolic pathways [ 58 ]. This hypothesis is supported by the discovery of mtDNA variations in Beata’s study, specifically in the mt-12S rRNA region, which can impact the oxidative capacity of the respiratory chain.…”