Preoperative Diagnosis and Molecular Characterization of Gliomas With Liquid Biopsy and Radiogenomics

Abstract

Gliomas are a heterogenous group of central nervous system tumors with different outcomes and different therapeutic needs. Glioblastoma, the most common subtype in adults, has a very poor prognosis and disabling consequences. The World Health Organization (WHO) classification specifies that the typing and grading of gliomas should include molecular markers. The molecular characterization of gliomas has implications for prognosis, treatment planning, and prediction of treatment response. At present, gliomas are diagnosed via tumor resection or biopsy, which are always invasive and frequently risky methods. In recent years, however, substantial advances have been made in developing different methods for the molecular characterization of tumors through the analysis of products shed in body fluids. Known as liquid biopsies, these analyses can potentially provide diagnostic and prognostic information, guidance on choice of treatment, and real-time information on tumor status. In addition, magnetic resonance imaging (MRI) is another good source of tumor data; radiomics and radiogenomics can link the imaging phenotypes to gene expression patterns and provide insights to tumor biology and underlying molecular signatures. Machine and deep learning and computational techniques can also use quantitative imaging features to non-invasively detect genetic mutations. The key molecular information obtained with liquid biopsies and radiogenomics can be useful not only in the diagnosis of gliomas but can also help predict response to specific treatments and provide guidelines for personalized medicine. In this article, we review the available data on the molecular characterization of gliomas using the non-invasive methods of liquid biopsy and MRI and suggest that these tools could be used in the future for the preoperative diagnosis of gliomas.

Keywords: diagnosis; glioblastoma; glioma; liquid biopsy; noninvasive; preoperative; radiogenomics; radiomics.

Figure 1

Elements of the liquid biopsy. B lymph, B lymphocyte; CSF, cerebrospinal fluid; cfDNA, cell-free DNA; CTC, circulating tumor cells; ctDNA, circulating tumor DNA; lnc RNA, long non-coding RNA; NK, natural killers; TEP, tumor-educated platelets; T lymph, T lymphocyte; miRNA, microRNA. Extracellular vesicles include exosomes, microvesicles and apoptotic vesicles.

Figure 2

Liquid biopsy obtained from blood or CSF. BBB, brain-blood barrier; CSF, cerebrospinal fluid; ctDNA, circulating tumor DNA; GWM, genome wide methylation; NGS, next generation sequencing; VPS, ventricular-peritoneal shunt.

Figure 3

Grade 4 IDH-mutant astrocytoma. (A) axial FLAIR, (B) axial T2-weighted image, (C) axial T1-weighted image with contrast, and (D) ADC map in the superior aspect of the lesion, showing a large infiltrative and expansive insular lesion. Note the partial T2-FLAIR mismatch sign at its lateral margin (circle) and extensive NCE component with no or only subtle enhancement with high ADC values. These findings indicate IDH-mutant astrocytoma. In contrast, the inferior aspect of the lesion (E–H) has a more heterogeneous T2 signal with hypointense areas corresponding to low ADC values and elevated rCBV in perfusion map (I) and intense poorly delimited enhancement with small necrotic areas. These findings indicate a high-grade tumor.