Recent advances in the use of liquid biopsy to fight central nervous system tumors.

Brain tumors are considered one of the deadliest types of cancer, being challenging to treat, especially due to the blood-brain barrier, which has been linked to treatment resistance. The genomic classification of brain tumors has been helping in the diagnostic precision, however tumor heterogeneity in addition to the difficulties to obtain tissue biopsies, represent a challenge. The biopsies are usually obtained either via neurosurgical removal or stereotactic tissue biopsy, which can be risky procedures for the patient. To overcome these challenges, liquid biopsy has become an interesting option by constituting a safer procedure than conventional biopsy, which may offer valuable cellular and molecular information representative of the whole organism. Besides, it is relatively easy to obtain such as in the case of blood (venipuncture) and urine sample collection. In the present comprehensive review, we discuss the newest information regarding liquid biopsy in the brain tumors' field, methods employed, the different sources of bio-fluids and their potential circulating targets.

Diagnostic value of fusion of metabolic and structural images for stereotactic biopsy of brain tumors without enhancement after contrast medium injection.

BACKGROUND: The heterogeneous nature of glioma makes it difficult to select a target for stereotactic biopsy that will be representative of grade severity on non-contrast-enhanced lesion imaging. The objective of this study was to evaluate the benefit of fusion of metabolic images (PET 18F-DOPA) with magnetic resonance imaging (MRI) morphological images for cerebral biopsy under stereotactic conditions of glioma without contrast enhancement. PATIENTS AND METHODS: This single-center prospective observational study conducted between January 2016 and April 2018 included 20 consecutive patients (mean age: 45±19.5 years; range, 9-80 years) who underwent cerebral biopsy for a tumor without MRI enhancement but with hypermetabolism on 18F-FDOPA PET (positron emission tomography). Standard 18F-FDOPA uptake value (SUVmax) was determined for diagnosis of high-grade glioma, with comparison to histomolecular results. RESULTS: Histological diagnosis was made in all patients (100%). Samples from hypermetabolism areas revealed high-grade glial tumor in 16 patients (80%). For a SUVmax threshold of 1.75, sensitivity was 81.2%, specificity 50%, PPV 86.7% and VPN 40% for diagnosis of high-grade glioma. No significant association between SUVmax and histomolecular mutation was found. CONCLUSION: 18F-FDOPA metabolic imaging is an aid in choosing the target to be biopsied under stereotactic conditions in tumors without MR enhancement. Nevertheless, despite good sensitivity, 18F-FDOPA PET is insufficient for definitive diagnosis of high-grade tumor.

Correlation of (18)F-fluoroethyl tyrosine positron-emission tomography uptake values and histomorphological findings by stereotactic serial biopsy in newly diagnosed brain tumors using a refined software tool.

BACKGROUND: Magnetic resonance imaging (MRI) is the standard neuroimaging method to diagnose neoplastic brain lesions, as well as to perform stereotactic biopsy surgical planning. MRI has the advantage of providing structural anatomical details with high sensitivity, though histological specificity is limited. Although combining MRI with other imaging modalities, such as positron-emission tomography (PET), has proven to increment specificity, exact correlation between PET threshold uptake ratios (URs) and histological diagnosis and grading has not yet been described. OBJECTIVES: The aim of this study was to correlate exactly the histopathological criteria of the biopsy site to its PET uptake value with high spatial resolution (mm(3)), and to analyze the diagnostic value of PET using the amino acid O-(2-[(18)F]fluoroethyl)-l-tyrosine ((18)F-FET) PET in patients with newly diagnosed brain lesions in comparison to histological findings obtained from stereotactic serial biopsy. PATIENTS AND METHODS: A total of 23 adult patients with newly diagnosed brain tumors on MRI were enrolled in this study. Subsequently to diagnoses, all patients underwent a (18)F-FET PET-guided stereotactic biopsy, using an original newly developed software module, which is presented here. Conventional MRI, stereotactic computed tomography series, and (18)F-FET PET images were semiautomatically fused, and hot-spot detection was performed for target planning. UR was determined using the uptake value from the biopsy sites in relation to the contralateral frontal white matter. UR values ≥1.6 were considered positive for glioma. High-grade glioma (HGG) was suspected with URs ≥3.0, while low-grade glioma (LGG) was suspected with URs between 1.6 and 3.0. Stereotactic serial biopsies along the trajectory at multiple sites were performed in millimeter steps, and the FET URs for each site were correlated exactly with a panel of 27 different histopathological markers. Comparisons between FET URs along the biopsy trajectories and the histological diagnoses were made with Pearson product-moment correlation coefficients. Analysis of variance was performed to test for significant differences in maximum UR between different tumor grades. RESULTS: A total of 363 biopsy specimens were taken from 23 patients by stereotactic serial biopsies. Histological examination revealed eight patients (35%) with an LGG: one with a World Health Organization (WHO)-I lesion and seven with a WHO-II lesion. Thirteen (57%) patients revealed an HGG (two with a WHO-III and three with a WHO-IV tumor), and two patients (9%) showed a process that was neither HGG nor LGG (group X or no-grade group). The correlation matrix between histological findings and the UR revealed five strong correlations. Low cell density in tissue samples was found to have a significant negative correlation with the measured cortical uptake rate (r=-0.43, P=0.02), as well as moderate cell density (r=-0.48, P=0.02). Pathological patterns of proliferation (r=0.37, P=0.04), GFAP (r=0.37, P=0.04), and Olig2 (r=0.36, P=0.05) showed a significant positive correlation with cortical URs. Analysis of variance tests showed a significant difference between the LGG and the HGG groups (F=8.27, P<0.002), but no significant differences when differentiating between the X group and the HGG (P=0.2)/LGG (P=0.8) groups, nor between the no-grade group and the WHO-I group. CONCLUSION: (18)F-FET PET is a valuable tool, as it allows the differentiation of HGGs from LGGs. Its use is not limited to preoperative evaluation; it may also refine biopsy targeting and improve tumor delimitation for radiotherapy. Histology is still necessary, and remains the gold standard for definitive diagnosis of brain lesions.