Primary CNS Lymphomas: Challenges in Diagnosis and Monitoring

Primary Central Nervous System Lymphoma (PCNSL) is a rare neoplasm that can involve brain, eye, leptomeninges, and rarely spinal cord. PCNSL lesions most typically enhance homogeneously on T1-weighted magnetic resonance imaging (MRI) and appear T2-hypointense, but high variability in MRI features is commonly encountered. Neurological symptoms and MRI findings may mimic high grade gliomas (HGGs), tumefactive demyelinating lesions (TDLs), or infectious and granulomatous diseases. Advanced MRI techniques (MR diffusion, spectroscopy, and perfusion) and metabolic imaging, such as Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) or amino acid PET (usually employing methionine), may be useful in distinguishing these different entities and monitoring the disease course. Moreover, emerging data suggest a role for cerebrospinal fluid (CSF) markers in predicting prognosis and response to treatments. In this review, we will address the challenges in PCNSL diagnosis, assessment of response to treatments, and evaluation of potential neurotoxicity related to chemotherapy and radiotherapy

Liquid biopsy for improving diagnosis and monitoring of CNS lymphomas:A RANO review

BACKGROUND: The utility of liquid biopsies is well documented in several extracranial and intracranial (brain/leptomeningeal metastases, gliomas) tumors. METHODS: The RANO (Response Assessment in Neuro-Oncology) group has set up a multidisciplinary Task Force to critically review the role of blood and cerebrospinal fluid (CSF)-liquid biopsy in CNS lymphomas, with a main focus on primary central nervous system lymphomas (PCNSL). RESULTS: Several clinical applications are suggested: diagnosis of PCNSL in critical settings (elderly or frail patients, deep locations, and steroid responsiveness), definition of minimal residual disease, early indication of tumor response or relapse following treatments, and prediction of outcome. CONCLUSIONS: Thus far, no clinically validated circulating biomarkers for managing both primary and secondary CNS lymphomas exist. There is need of standardization of biofluid collection, choice of analytes, and type of technique to perform the molecular analysis. The various assays should be evaluated through well-organized central testing within clinical trials.</p

Liquid biopsy for improving diagnosis and monitoring of CNS lymphomas:A RANO review

BACKGROUND: The utility of liquid biopsies is well documented in several extracranial and intracranial (brain/leptomeningeal metastases, gliomas) tumors. METHODS: The RANO (Response Assessment in Neuro-Oncology) group has set up a multidisciplinary Task Force to critically review the role of blood and cerebrospinal fluid (CSF)-liquid biopsy in CNS lymphomas, with a main focus on primary central nervous system lymphomas (PCNSL). RESULTS: Several clinical applications are suggested: diagnosis of PCNSL in critical settings (elderly or frail patients, deep locations, and steroid responsiveness), definition of minimal residual disease, early indication of tumor response or relapse following treatments, and prediction of outcome. CONCLUSIONS: Thus far, no clinically validated circulating biomarkers for managing both primary and secondary CNS lymphomas exist. There is need of standardization of biofluid collection, choice of analytes, and type of technique to perform the molecular analysis. The various assays should be evaluated through well-organized central testing within clinical trials.</p

Advanced MR techniques for preoperative glioma characterization: Part 1

Preoperative clinical magnetic resonance imaging (MRI) protocols for gliomas, brain tumors with dismal outcomes due to their infiltrative properties, still rely on conventional structural MRI, which does not deliver information on tumor genotype and is limited in the delineation of diffuse gliomas. The GliMR COST action wants to raise awareness about the state of the art of advanced MRI techniques in gliomas and their possible clinical translation or lack thereof. This review describes current methods, limits, and applications of advanced MRI for the preoperative assessment of glioma, summarizing the level of clinical validation of different techniques. In this first part, we discuss dynamic susceptibility contrast and dynamic contrast-enhanced MRI, arterial spin labeling, diffusion-weighted MRI, vessel imaging, and magnetic resonance fingerprinting. The second part of this review addresses magnetic resonance spectroscopy, chemical exchange saturation transfer, susceptibility-weighted imaging, MRI-PET, MR elastography, and MR-based radiomics applications. Evidence Level: 3 Technical Efficacy: Stage 2

Brain Tumor Characterization Using Radiogenomics in Artificial Intelligence Framework

Brain tumor characterization (BTC) is the process of knowing the underlying cause of brain tumors and their characteristics through various approaches such as tumor segmentation, classification, detection, and risk analysis. The substantial brain tumor characterization includes the identification of the molecular signature of various useful genomes whose alteration causes the brain tumor. The radiomics approach uses the radiological image for disease characterization by extracting quantitative radiomics features in the artificial intelligence (AI) environment. However, when considering a higher level of disease characteristics such as genetic information and mutation status, the combined study of “radiomics and genomics” has been considered under the umbrella of “radiogenomics”. Furthermore, AI in a radiogenomics’ environment offers benefits/advantages such as the finalized outcome of personalized treatment and individualized medicine. The proposed study summarizes the brain tumor’s characterization in the prospect of an emerging field of research, i.e., radiomics and radiogenomics in an AI environment, with the help of statistical observation and risk-of-bias (RoB) analysis. The PRISMA search approach was used to find 121 relevant studies for the proposed review using IEEE, Google Scholar, PubMed, MDPI, and Scopus. Our findings indicate that both radiomics and radiogenomics have been successfully applied aggressively to several oncology applications with numerous advantages. Furthermore, under the AI paradigm, both the conventional and deep radiomics features have made an impact on the favorable outcomes of the radiogenomics approach of BTC. Furthermore, risk-of-bias (RoB) analysis offers a better understanding of the architectures with stronger benefits of AI by providing the bias involved in them

Advanced Neuroimaging in Brain Tumors : Diffusion, Spectroscopy, Perfusion and Permeability MR imaging for the evaluation of tumor characterization and surgical treatment planning.

Advanced Neuroimaging in Brain Tumors: Diffusion, Spectroscopy, Perfusion and Permeability for the evaluation of tumor characterization and surgical treatment planning. The current standard of neuroimaging for brain tumor evaluation is anatomy-based MRI. Unfortunately, MRI does not fully reflect the complicated biology of infiltrative glioma, and has a limited capacity to differentiate a high-grade glioma (HGG) from a single brain metastasis. Grading of gliomas is important for the determination of appropriate treatment strategies and in the assessment of prognosis. It is clinically important to distinguish HGG from a single brain metastasis, because medical staging, surgical planning, and therapeutic decisions are different for each tumor type. The basis for this thesis was 208 patients admitted at Oslo University Hospital-Ullevål with the diagnosis of brain tumor between 2006 and 2010. The aim of this thesis was to evaluate in terms of diagnostic examination performance in the clinical decision-making process the use of advanced MRI techniques, namely, diffusion-weighted imaging (DWI), magnetic resonance spectroscopic imaging (MRSI), and T2*-weighted first pass dynamic susceptibility contrast-enhanced perfusion MRI (DSC MRI) in the diagnosis and preoperative planning of brain tumors, with focus in the grading and characterization of gliomas, as well as in the assessment of the peri-enhancing region aiming to demonstrate tumor-infiltration and tumor-free edema. In this thesis, we have demonstrated that MRSI and DSC MRI can be helpful to discriminate HGG from solitary metastases, supporting the hypothesis that these advanced MRI techniques can detect infiltration of tumor cells in the peri-enhancing region. We have demonstrated that combining DWI and MRSI increases the accuracy in the determination of glioma grade. We identified differences among all glial tumor grades for the parameters cerebral blood volume (rCBV) and microvascular leakage (MVL) derived from DSC MRI. Our correlation analysis indicate that MVL, rCBV, and cerebral blood flow (rCBF) may be related to different aspects of tumor angiogeneseis

Rare Primary Central Nervous System Tumors in Adults: An Overview

Overall, tumors of primary central nervous system (CNS) are quite common in adults with an incidence rate close to 30 new cases/100,000 inhabitants per year. Significant clinical and biological advances have been accomplished in the most common adult primary CNS tumors (i.e., diffuse gliomas). However, most CNS tumor subtypes are rare with an incidence rate below the threshold defining rare disease of 6.0 new cases/100,000 inhabitants per year. Close to 150 entities of primary CNS tumors have now been identified by the novel integrated histomolecular classification published by the World Health Organization (WHO) and its updates by the c-IMPACT NOW consortium (the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy). While these entities can be better classified into smaller groups either by their histomolecular features and/or by their location, assessing their treatment by clinical trials and improving the survival of patients remain challenging. Despite these tumors are rare, research, and advances remain slower compared to diffuse gliomas for instance. In some cases (i.e., ependymoma, medulloblastoma) the understanding is high because single or few driver mutations have been defined. The European Union has launched European Reference Networks (ERNs) dedicated to support advances on the clinical side of rare diseases including rare cancers. The ERN for rare solid adult tumors is termed EURACAN. Within EURACAN, Domain 10 brings together the European patient advocacy groups (ePAGs) and physicians dedicated to improving outcomes in rare primary CNS tumors and also aims at supporting research, care and teaching in the field. In this review, we discuss the relevant biological and clinical characteristics, clinical management of patients, and research directions for the following types of rare primary CNS tumors: medulloblastoma, pineal region tumors, glioneuronal and rare glial tumors, ependymal tumors, grade III meningioma and mesenchymal tumors, primary central nervous system lymphoma, germ cell tumors, spinal cord tumors and rare pituitary tumors