Neuro-Oncology
Reviews


Volume 22 Supplement 4
October 2020


Home > Publications > Neuro-Oncology Reviews > Volume 22, Year 2020 > Supplement 4, October



Contents


Central nervous system tumors


Gliomas


High-grade gliomas


Diffuse astrocytic and oligodendroglial tumors


Glioblastoma


Embryonal tumors


Medulloblastoma


Atypical theratoid/rhabdoid tumor


Meningiomas


Meningioma


Metastatic tumors



Central nervous system tumors


Cohen KJ et al, PDQ Pediatric Treatment Editorial Board.
Childhood Brain and Spinal Cord Tumors Treatment Overview (PDQ®): Health Professional Version.
PDQ Cancer Inf Summ. 2020 Oct 9. NCBI Bookshelf: NBK66018. _


Primary brain tumors are a diverse group of diseases that together constitute the most common solid tumor of childhood. The Central Brain Tumor Registry of the United States (CBTRUS) estimates that approximately 4,300 U.S. children are diagnosed each year. Brain tumors are classified by histology, but tumor location and extent of spread are also important factors that affect treatment and prognosis. Immunohistochemical analysis, cytogenetic and molecular genetic findings, and measures of proliferative activity are increasingly used in tumor diagnosis and classification. Dramatic improvements in survival have been achieved for children and adolescents with cancer. Between 1975 and 2010, childhood cancer mortality decreased by more than 50%. Childhood and adolescent cancer survivors require close monitoring because cancer therapy side effects may persist or develop months or years after treatment. Refer to the PDQ summary on Late Effects of Treatment for Childhood Cancer for specific information about the incidence, type, and monitoring of late effects in childhood and adolescent cancer survivors.




Karmur BS, Philteos J, Abbasian A, Zacharia BE, Lipsman N, Levin V, Grossman S, Mansouri A.
Blood-Brain Barrier Disruption in Neuro-Oncology: Strategies, Failures, and Challenges to Overcome.
Front Oncol. 2020 Sep 18. 2020;10:563840. doi: 10.3389/fonc.2020.563840. Review. _


The blood-brain barrier (BBB) presents a formidable challenge in the development of effective therapeutics in neuro-oncology. This has fueled several decades of efforts to develop strategies for disrupting the BBB, but progress has not been satisfactory. As such, numerous drug- and device-based methods are currently being investigated in humans. Through a focused assessment of completed, active, and pending clinical trials, our first aim in this review is to outline the scientific foundation, successes, and limitations of the BBBD strategies developed to date. Among 35 registered trials relevant to BBBD in neuro-oncology in the ClinicalTrials.gov database, mannitol was the most common drug-based method, followed by RMP-7 and regadenoson. MR-guided focused ultrasound was the most common device-based method, followed by MR-guided laser ablation, ultrasound, and transcranial magnetic stimulation. While most early-phase studies focusing on safety and tolerability have met stated objectives, advanced-phase studies focusing on survival differences and objective tumor response have been limited by heterogeneous populations and tumors, along with a lack of control arms. Based on shared challenges among all methods, our second objective is to discuss strategies for confirmation of BBBD, choice of systemic agent and drug design, alignment of BBBD method with real-world clinical workflow, and consideration of inadvertent toxicity associated with disrupting an evolutionarily-refined barrier. Finally, we conclude with a strategic proposal to approach future studies assessing BBBD.




Montoya ML, Kasahara N, Okada H.
Introduction to immunotherapy for brain tumor patients: challenges and future perspectives.
Neurooncol Pract. 2020 Mar 9. 2020;7(5):465-476. doi: 10.1093/nop/npaa007. Review. _


Malignant gliomas, including glioblastoma (GBM) as the most aggressive type of adult CNS tumors, are notoriously resistant to current standard of care treatments, including surgery, systemic chemotherapy, and radiation therapy (RT). This lack of effective treatment options highlights the urgent need for novel therapies, including immunotherapies. The overarching goal of immunotherapy is to stimulate and activate the patient's immune system in a targeted manner to kill tumor cells. The success of immunotherapeutic interventions in other cancer types has led to interest in and evaluation of various experimental immunotherapies in patients with malignant gliomas. However, these primary malignant brain tumors present a challenge because they exist in a vital and sensitive organ with a unique immune environment. The challenges and current status of experimental immunotherapeutic approaches, including vaccines, immune-checkpoint blockade, chimeric antigen receptor T-cell therapy, and oncolytic viruses will be discussed, as well as the potential for combinatorial therapies.




Somme F, Bender L, Namer IJ, Noël G, Bund C.
Usefulness of 18F-FDOPA PET for the management of primary brain tumors: a systematic review of the literature.
Cancer Imaging. 2020 Oct 6. 2020;20(1):70. doi: 10.1186/s40644-020-00348-5. Review. _


Contrast-enhanced magnetic resonance imaging is currently the standard of care in the management of primary brain tumors, although certain limitations remain. Metabolic imaging has proven useful for an increasing number of indications in oncology over the past few years, most particularly 18F-FDG PET/CT. In neuro-oncology, 18F-FDG was insufficient to clearly evaluate brain tumors. Amino-acid radiotracers such as 18F-FDOPA were then evaluated in the management of brain diseases, notably tumoral diseases. Even though European guidelines on the use of amino-acid PET in gliomas have been published, it is crucial that future studies standardize acquisition and interpretation parameters. The aim of this article was to systematically review the potential effect of this metabolic imaging technique in numerous steps of the disease: primary and recurrence diagnosis, grading, local and systemic treatment assessment, and prognosis. A total of 41 articles were included and analyzed in this review. It appears that 18F-FDOPA PET holds promise as an effective additional tool in the management of gliomas. More consistent prospective studies are still needed.




Unkelbach J, Bortfeld T, Cardenas CE, Gregoire V, Hager W, Heijmen B, Jeraj R, Korreman SS, Ludwig R, Pouymayou B, Shusharina N, Söderberg J, Toma-Dasu I, Troost EGC, Vasquez Osorio E.
The role of computational methods for automating and improving clinical target volume definition.
Radiother Oncol. 2020 Oct 7. doi: 10.1016/j.radonc.2020.10.002. Review. _


Treatment planning in radiotherapy distinguishes three target volume concepts: the gross tumor volume (GTV), the clinical target volume (CTV), and the planning target volume (PTV). Over time, GTV definition and PTV margins have improved through the development of novel imaging techniques and better image guidance, respectively. CTV definition is sometimes considered the weakest element in the planning process. CTV definition is particularly complex since the extension of microscopic disease cannot be seen using currently available in-vivo imaging techniques. Instead, CTV definition has to incorporate knowledge of the patterns of tumor progression. While CTV delineation has largely been considered the domain of radiation oncologists, this paper, arising from a 2019 ESTRO Physics research workshop, discusses the contributions that medical physics and computer science can make by developing computational methods to support CTV definition. First, we overview the role of image segmentation algorithms, which may in part automate CTV delineation through segmentation of lymph node stations or normal tissues representing anatomical boundaries of microscopic tumor progression. The recent success of deep convolutional neural networks has also enabled learning entire CTV delineations from examples. Second, we discuss the use of mathematical models of tumor progression for CTV definition, using as example the application of glioma growth models to facilitate GTV-to-CTV expansion for glioblastoma that is consistent with neuroanatomy. We further consider statistical machine learning models to quantify lymphatic metastatic progression of tumors, which may eventually improve elective CTV definition. Lastly, we discuss approaches to incorporate uncertainty in CTV definition into treatment plan optimization as well as general limitations of the CTV concept in the case of infiltrating tumors without natural boundaries.



Gliomas


Ghosh MK, Chakraborty D, Sarkar S, Bhowmik A, Basu M.
The interrelationship between cerebral ischemic stroke and glioma: a comprehensive study of recent reports.
Signal Transduct Target Ther. 2019 Oct 12. 2019;4(1):42. doi: 10.1038/s41392-019-0075-4. Review. _


Glioma and cerebral ischemic stroke are two major events that lead to patient death worldwide. Although these conditions have different physiological incidences, ~10% of ischemic stroke patients develop cerebral cancer, especially glioma, in the postischemic stages. Additionally, the high proliferation, venous thrombosis and hypercoagulability of the glioma mass increase the significant risk of thromboembolism, including ischemic stroke. Surprisingly, these events share several common pathways, viz. hypoxia, cerebral inflammation, angiogenesis, etc., but the proper mechanism behind this co-occurrence has yet to be discovered. The hypercoagulability and presence of the D-dimer level in stroke are different in cancer patients than in the noncancerous population. Other factors such as atherosclerosis and coagulopathy involved in the pathogenesis of stroke are partially responsible for cancer, and the reverse is also partially true. Based on clinical and neurosurgical experience, the neuronal structures and functions in the brain and spine are observed to change after a progressive attack of ischemia that leads to hypoxia and atrophy. The major population of cancer cells cannot survive in an adverse ischemic environment that excludes cancer stem cells (CSCs). Cancer cells in stroke patients have already metastasized, but early-stage cancer patients also suffer stroke for multiple reasons. Therefore, stroke is an early manifestation of cancer. Stroke and cancer share many factors that result in an increased risk of stroke in cancer patients, and vice-versa. The intricate mechanisms for stroke with and without cancer are different. This review summarizes the current clinical reports, pathophysiology, probable causes of co-occurrence, prognoses, and treatment possibilities.




Rius-Rocabert S, García-Romero N, García A, Ayuso-Sacido A, Nistal-Villan E.
Oncolytic Virotherapy in Glioma Tumors.
Int J Mol Sci. 2020 Oct 14. 2020;21(20):7604. doi: 10.3390/ijms21207604. Review. _


Glioma tumors are one of the most devastating cancer types. Glioblastoma is the most advanced stage with the worst prognosis. Current therapies are still unable to provide an effective cure. Recent advances in oncolytic immunotherapy have generated great expectations in the cancer therapy field. The use of oncolytic viruses (OVs) in cancer treatment is one such immune-related therapeutic alternative. OVs have a double oncolytic action by both directly destroying the cancer cells and stimulating a tumor specific immune response to return the ability of tumors to escape the control of the immune system. OVs are one promising alternative to conventional therapies in glioma tumor treatment. Several clinical trials have proven the feasibility of using some viruses to specifically infect tumors, eluding undesired toxic effects in the patient. Here, we revisited the literature to describe the main OVs proposed up to the present moment as therapeutic alternatives in order to destroy glioma cells in vitro and trigger tumor destruction in vivo. Oncolytic viruses were divided with respect to the genome in DNA and RNA viruses. Here, we highlight the results obtained in various clinical trials, which are exploring the use of these agents as an alternative where other approaches provide limited hope.



High-grade gliomas



Crooms RC, Goldstein NE, Diamond EL, Vickrey BG.
Palliative Care in High-Grade Glioma: A Review.
Brain Sci. 2020 Oct 13. 2020;10(10):723. doi: 10.3390/brainsci10100723. Review. _


High-grade glioma (HGG) is characterized by debilitating neurologic symptoms and poor prognosis. Some of the su ering this disease engenders may be ameliorated through palliative care, which improves quality of life for seriously ill patients by optimizing symptom management and psychosocial support, which can be delivered concurrently with cancer-directed treatments. In this article, we review palliative care needs associated with HGG and identify opportunities for primary and specialty palliative care interventions. Patients with HGG and their caregivers experience high levels of distress due to physical, emotional, and cognitive symptoms that negatively impact quality of life and functional independence, all in the context of limited life expectancy. However, patients typically have limited contact with specialty palliative care until the end of life, and there is no established model for ensuring their palliative care needs are met throughout the disease course. We identify low rates of advance care planning, misconceptions about palliative care being synonymous with end-of-life care, and the unique neurologic needs of this patient population as some of the potential barriers to increased palliative interventions. Further research is needed to define the optimal roles of neuro-oncologists and palliative care specialists in the management of this illness and to establish appropriate timing and models for palliative care delivery.



Diffuse astrocytic and oligodendroglial tumors


Birkó Z, Nagy B, Klekner Á, Virga J.
Novel Molecular Markers in Glioblastoma.Benefits of Liquid Biopsy.
Int J Mol Sci. 2020 Oct 12. 2020;21(20):7522. doi: 10.3390/ijms21207522. Review. _


Glioblastoma is a primary Central Nervous System (CNS) malignancy with poor survival. Treatment options are scarce and despite the extremely heterogeneous nature of the disease, clinicians lack prognostic and predictive markers to characterize patients with different outcomes. Certain immunohistochemistry, FISH, or PCR-based molecular markers, including isocitrate dehydrogenase1/2 (IDH1/2) mutations, epidermal growth factor receptor variant III (EGFRvIII) mutation, vascular endothelial growth factor overexpression (VEGF) overexpression, or (O6-Methylguanine-DNA methyltransferase promoter) MGMT promoter methylation status, are well-described; however, their clinical usefulness and accuracy is limited, and tumor tissue samples are always necessary. Liquid biopsy is a developing field of diagnostics and patient follow up in multiple types of cancer. Fragments of circulating nucleic acids are collected in various forms from different bodily fluids, including serum, urine, or cerebrospinal fluid in order to measure the quality and quantity of these markers. Multiple types of nucleic acids can be analyzed using liquid biopsy. Circulating cell-free DNA, mitochondrial DNA, or the more stable long and small non-coding RNAs, circular RNAs, or microRNAs can be identified and measured by novel PCR and next-generation sequencing-based methods. These markers can be used to detect the previously described alterations in a minimally invasive method. These markers can be used to differentiate patients with poor or better prognosis, or to identify patients who do not respond to therapy. Liquid biopsy can be used to detect recurrent disease, often earlier than using imaging modalities. Liquid biopsy is a rapidly developing field, and similarly to other types of cancer, measuring circulating tumor-derived nucleic acids from biological fluid samples could be the future of differential diagnostics, patient stratification, and follow up in the future in glioblastoma as well.




Kapoor M, Gupta V.
Astrocytoma.
StatPearls. 2020 Oct 5. NCBI Bookshelf: NBK558954. Review. _


Astrocytoma originates in astrocytes, which are a kind of glial cells in the cerebrum which are star-shaped. It is the most common glioma, usually affecting the brain and sometimes the spinal cord. Amongst brain tumors,  glial tumors comprise 60% of the tumors. They are a common cause of mortality and morbidity in both the young and old.




Jin L, Guo S, Zhang X, Mo Y, Ke S, Duan C.
Optimal treatment strategy for adult patients with newly diagnosed glioblastoma: a systematic review and network meta-analysis.
Neurosurg Rev. 2020 Oct 10. doi: 10.1007/s10143-020-01403-2. Review and meta-analysis. _


To compare the efficacy and safety of treatments based on the Stupp protocol for adult patients with newly diagnosed glioblastoma and to determine the optimal treatment option for patients with different O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation statuses. We estimated hazard ratios (HRs) for overall survival (OS) and odds ratios (ORs) for adverse events of grade 3 or higher (AEs ≥ 3). Twenty-one randomized controlled trials involving 6478 patients treated with 21 different treatment strategies were included. Results of the pooled HRs indicated tumor-treating fields (TTF) combined with the Stupp protocol resulted in the most favorable OS for patients with and without MGMT promoter methylation. Subgroup analyses by the two MGMT promoter statuses indicated that lomustinetemozolomide plus radiotherapy or TTF combination therapy was associated with the best OS for patients with methylated MGMT promoter (HR, 1.03; 95% credible interval [CI], 0.54–1.97), and standard cilengitide combination therapy or TTF combination treatment was associated with the best OS for patients with unmethylated MGMT promoter (HR, 1.05; 95% CI, 0.67–1.64). Regarding AEs ≥ 3, there were no significant differences in pooled ORs. However, Bayesian ranking profiles that demonstrated intensive cilengitide combination therapy and TTF combination therapy have a similar possibility to cause the least toxicity. These results indicated that TTF combination therapy was associated with increased survival, irrespective of the MGMTpromoter methylation status, and a relatively tolerated safety profile compared with other combination treatments. The optimal treatment option for glioblastoma patients with different MGMT promoter methylation statuses was different.



Glioblastoma



Atiq A, Parhar I.
Anti-neoplastic Potential of Flavonoids and Polysaccharide Phytochemicals in Glioblastoma.
Molecules. 2020 Oct 23. 2020;25(21):4895. doi: 10.3390/molecules25214895. Review.
_


Clinically, gliomas are classified into four grades, with grade IV glioblastoma multiforme being the most malignant and deadly, which accounts for 50% of all gliomas. Characteristically, glioblastoma involves the aggressive proliferation of cells and invasion of normal brain tissue, outcomes as poor patient prognosis. With the current standard therapy of glioblastoma; surgical resection and radiotherapy followed by adjuvant chemotherapy with temozolomide, it remains fatal, because of the development of drug resistance, tumor recurrence, and metastasis. Therefore, the need for the effective therapeutic option for glioblastoma remains elusive. Previous studies have demonstrated the chemopreventive role of naturally occurring pharmacological agents through preventing or reversing the initiation phase of carcinogenesis or arresting the cancer progression phase. In this review, we discuss the role of natural phytochemicals in the amelioration of glioblastoma, with the aim to improve therapeutic outcomes, and minimize the adverse side effects to improve patient’s prognosis and enhancing their quality of life.




Brancato V, Nuzzo S, Tramontano L, Condorelli G, Salvatore M, Cavaliere C.
Predicting Survival in Glioblastoma Patients Using Diffusion MR Imaging MetricsA Systematic Review.
Cancers (Basel). 2020 Oct 4. 2020;12(10):2858. doi: 10.3390/cancers12102858. Review. _


An accurate survival analysis is crucial for disease management in glioblastoma (GBM) patients. Due to the ability of the diffusion MRI techniques of providing a quantitative assessment of GBM tumours, an ever-growing number of studies aimed at investigating the role of diffusion MRI metrics in survival prediction of GBM patients. Since the role of diffusion MRI in prediction and evaluation of survival outcomes has not been fully addressed and results are often controversial or unsatisfactory, we performed this systematic review in order to collect, summarize and evaluate all studies evaluating the role of diffusion MRI metrics in predicting survival in GBM patients. We found that quantitative diffusion MRI metrics provide useful information for predicting survival outcomes in GBM patients, mainly in combination with other clinical and multimodality imaging parameters.




Cebula H, Noel G, Garnon J, Todeschi J, Burckel H, de Mathelin M, Gangi A, Proust F.
The Cryo-immunologic effect: A therapeutic advance in the treatment of glioblastomas?
Neurochirurgie. 2020 Oct 10. doi: 10.1016/j.neuchi.2020.06.135. Review; _


The immunotherapy of cerebral glioblastoma has become a hot topic. Immune checkpoint blockade antibodies have progressively acquired a role in the management of malignant tumors. A multimodal approach using surgery, radiotherapy, chemotherapy in combination with immunotherapy represent a potent weapon against glioblastomas. In parallel, clinical applications of cryotherapy–freezing tumors based on repetition of rapid freeze-slow thaw cycle–for various cancers such as skin, lung, breast, esophagus, hepatic, kidney, prostate and bone tumors were developed. The future immunomodulatory approaches might be combined with brain tumors cryoablation to increase the cryoimmune response. The objective of this study was to analyze from the literature the relationship between cerebral cryosurgery and immunomodulation using PRISMA method. The animals’ studies demonstrate the dendritic cells maturation and activation with the enhancement of antigen-presenting function after cryotherapy suggesting the potential usefulness of the association of cryotherapy and immunomodulator in the management of gliomas.




Desland FA, Hormigo A.
The CNS and the Brain Tumor Microenvironment: Implications for Glioblastoma Immunotherapy.
Int J Mol Sci. 2020 Oct 5. 2020;21(19):7358. doi: 10.3390/ijms21197358. Review. _


Glioblastoma (GBM) is the most common and aggressive malignant primary brain tumor in adults. Its aggressive nature is attributed partly to its deeply invasive margins, its molecular and cellular heterogeneity, and uniquely tolerant site of origin—the brain. The immunosuppressive central nervous system (CNS) and GBM microenvironments are significant obstacles to generating an e ffective and long-lasting anti-tumoral response, as evidenced by this tumor’s reduced rate of treatment response and high probability of recurrence. Immunotherapy has revolutionized patients’ outcomes across many cancers and may open new avenues for patients with GBM. There is now a range of immunotherapeutic strategies being tested in patients with GBM that target both the innate and adaptive immune compartment. These strategies include antibodies that re-educate tumor macrophages, vaccines that introduce tumor-specific dendritic cells, checkpoint molecule inhibition, engineered T cells, and proteins that help T cells engage directly with tumor cells. Despite this, there is still much ground to be gained in improving the response rates of the various immunotherapies currently being trialed. Through historical and contemporary studies, we examine the fundamentals of CNS immunity that shape how to approach immune modulation in GBM, including the now revamped concept of CNS privilege. We also discuss the preclinical models used to study GBM progression and immunity. Lastly, we discuss the immunotherapeutic strategies currently being studied to help overcome the hurdles of the blood–brain barrier and the immunosuppressive tumor microenvironment.




Kanderi T, Gupta V.
Glioblastoma Multiforme.
StatPearls. 2020 Oct 5. NCBI Bookshelf: NBK558954. Review. _


Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults accounting for 45.2% of malignant primary brain and CNS tumors. GBM remains an incurable disease with a median survival of 15 months. Only 5.5 % of patients survived five years post-diagnosis. GBMs comprises primary and secondary subtypes that evolve through different genetic pathways affecting patients at different ages with differences in outcomes. Primary GBMs account for 80% of GBMs and occur in older patients with a mean age of 62 yrs while secondary GBMs occur from lower-grade astrocytoma or oligodendroglioma in younger patients with a mean age of 45 years. Secondary GBMs are usually located in the frontal lobe, have a lesser degree of necrosis, and carry a better prognosis than primary GBMs. The World Health Organization defines GBM as a grade IV cancer characterized as malignant, mitotically active, and predisposed to necrosis. GBM has a very poor prognosis. …




Ponterio E, De Maria R, Haas TL.
Identification of Targets to Redirect CAR T Cells in Glioblastoma and Colorectal Cancer: An Arduous Venture.
Front Immunol. 2020 Sep 30. 2020;11:565631. doi: 10.3389/fimmu.2020.565631. Review. _


The chimeric antigen receptor (CAR) is an artificial molecule engineered to induce cytolytic T cell reactions in tumors. Generally, this molecule combines an extracellular single-chain variable fragment (scFv) able to recognize tumor-associated epitopes together with the intracellular signaling domains that are required for T cell activation. When expressed by T cells, the CAR enables the recognition and subsequent destruction of cancer cells expressing the complementary antigen on their surface. Although the clinical application for CAR T cells is currently limited to some hematological malignancies, researchers are trying to develop CAR T cell-based therapies for the treatment of solid tumors. However, while in the case of CD19, or other targets restricted to the hematopoietic compartment, the toxicity is limited and manageable, the scarcity of specific antigens expressed by solid tumors and not by healthy cells from vital organs makes the clinical development of CAR T cells in this context particularly challenging. Here we summarize relevant research and clinical trials conducted to redirect CAR T cells to surface antigens in solid tumors and cancer stem cells with a focus on colorectal cancer and glioblastoma. Finally, we will discuss current knowledge of altered glycosylation of CSCs and cancer cells and how these novel epitopes may help to target CAR T cell-based immunotherapy in the future.




Zhang JJY, Lee KS, Voisin MR, Hervey-Jumper SL, Berger MS, Zadeh G.
Awake craniotomy for resection of supratentorial glioblastoma: a systematic review and meta-analysis.
Neurooncol Adv. 2020 Sep 18. 2020;2(1):vdaa111. doi: 10.1093/noajnl/vdaa111. Review and meta-analysis. _


Background. The goal of glioblastoma (GBM) surgery is to maximize the extent of resection (EOR) while minimizing postoperative neurological complications. Awake craniotomy (AC) has been demonstrated to achieve this goal for low-grade gliomas in or near eloquent areas. However, the efficacy of AC for GBM resection has not been established. Therefore, we aimed to investigate the outcomes of AC for surgical resection of GBM using a systematic review and meta-analysis of published studies. Methods. Systematic searches of Ovid, MedLine, Embase, Cochrane Controlled Register of Controlled Trials, and PubMed were performed from database inception to September 14, 2019 for published studies reporting outcomes of AC for GBM resection. Outcome measures analyzed included EOR and the event rate of postoperative neurological deficits. Results. A total of 1928 unique studies were identified. Fourteen studies reporting 278 patients were included in our meta-analysis. Mean age of patients was 46.9 years (95% confidence interval [CI]: 43.9–49.9). Early and late postoperative neurological deficits occurred in 34.5% (95% CI: 21.9–48.2) and 1.9% (95% CI: 0.0–9.2) of patients, respectively. Pooled percentage of gross total resection (GTR) was 74.7% (95% CI: 66.7–82.1), while the pooled percentage reduction in tumor volume was 95.3% (95% CI: 92.2–98.4). Conclusions. Limited current evidence suggests that the use of AC for resection of supratentorial GBM is associated with a low rate of persistent neurological deficits while achieving an acceptable rate of GTR. Our findings demonstrate the potential viability of AC in GBM resection and highlight the need for further research on this topic.




Zhang P, Xia Q, Liu L, Li S, Dong L.
Current Opinion on Molecular Characterization for GBM Classification in Guiding Clinical Diagnosis, Prognosis, and Therapy.
Front Mol Biosci. 2020 Sep 8. 2020;7:562798. doi: 10.3389/fmolb.2020.562798. Review. _


Glioblastoma (GBM) is highly invasive and the deadliest brain tumor in adults. It is characterized by inter-tumor and intra-tumor heterogeneity, short patient survival, and lack of effective treatment. Prognosis and therapy selection is driven by molecular data from gene transcription, genetic alterations and DNA methylation. The four GBM molecular subtypes are proneural, neural, classical, and mesenchymal. More effective personalized therapy heavily depends on higher resolution molecular subtype signatures, combined with gene therapy, immunotherapy and organoid technology. In this review, we summarize the principal GBM molecular classifications that guide diagnosis, prognosis, and therapeutic recommendations.



Embryonal tumors



Medulloblastoma



Cohen KJ et al., PDQ Pediatric Treatment Editorial Board.
Childhood Medulloblastoma and Other Central Nervous System Embryonal Tumors Treatment (PDQ®): Health Professional Version.
PDQ Cancer Inf Summ. 2020 Oct 5. NCBI Bookshelf: NBK65981. Review. _


Embryonal tumors are a collection of biologically heterogeneous lesions that share the tendency to disseminate throughout the nervous system via cerebrospinal fluid (CSF) pathways. Although there is significant variability, histologically these tumors are grouped together because they are at least partially composed of hyperchromatic cells (blue cell tumors on standard staining) with little cytoplasm, which are densely packed and demonstrate a high degree of mitotic activity. Other histologic and immunohistochemical features, such as the degree of apparent cellular transformation along identifiable cell lineages (ependymal, glial, etc.), can be used to separate these tumors to some degree. However, a convention, which has been accepted by the WHO, also separates these tumors on the basis of presumed location of origin within the central nervous system (CNS). Molecular studies have substantiated the differences between tumors arising in different areas of the brain and give partial credence to this classification approach. …



Atypical theratoid/rhabdoid tumor



Nesvick CL, Lafay-Cousin L, Raghunathan A, Bouffet E, Huang AA, Daniels DJ.
Atypical teratoid rhabdoid tumor: molecular insights and translation to novel therapeutics.
J Neurooncol. 2020 Oct 6. doi: 10.1007/s11060-020-03639-w. Review. _


Introduction. Atypical teratoid rhabdoid tumor (ATRT) is a rare, often lethal brain tumor of childhood characterized by a complex epigenetic landscape amongst a simple genetic background. Recent molecular studies have defined key biologic events that contribute to tumorigenesis and molecular subtypes of ATRT. Methods. Seminal studies on ATRT are reviewed with an emphasis on molecular pathogenesis and its relevance to novel therapeutics. Results. In this review, we summarize the key clinicopathologic and molecular features of ATRT, completed and ongoing clinical trials and outline the translational potential of novel insights into the molecular pathogenesis of this tumor. Conclusions. SMARCB1 loss is the key genetic event in ATRT pathogenesis that leads to widespread epigenetic dysregulation and loss of lineage-specific enhancers. Current work is defining subtype-specific treatments that target underlying molecular derangements that drive tumorigenesis.



Meningiomas



Meningioma



Walsh KM.
Epidemiology of meningiomas.
Handb Clin Neurol. 2020 Jun 15. 2020;169:3-15. doi: 10.1016/B978-0-12-804280-9.00001-9. Book chapter. _


More than 70,000 primary central nervous system tumors are diagnosed in the United States each year. Approximately 36% of these are meningiomas, making it the most common primary brain tumor. Because meningioma risk increases dramatically with age, the healthcare burden of meningioma in the developed world will continue to rise as demographics shift toward an older population. In addition to demographic factors associated with increased meningioma risk (i.e., older age, female sex, African American ethnicity), increased body mass index is a strong risk factor. A history of atopic allergies, eczema, and increased serum IgE are all consistently associated with reduced meningioma risk, suggesting a potential role for immunosurveillance. Although ionizing radiation is a strong meningioma risk factor, it accounts for very few cases at the population level. Recent studies suggest that diagnostic radiation (e.g., dental X-rays) increases meningioma risk. Because radiation dosages associated with medical imaging have decreased dramatically, the public health impact of this exposure is likely in decline. Genome-wide association studies have identified common inherited variants in the gene MLLT10 and RIC8A as low-penetrance meningioma risk alleles.



Metastatic tumors


Arora RD, Cascella M.
Palliative Radiation Therapy For Brain Metastases.
StatPearls. 2020 Oct 11. NCBI Bookshelf: NBK563192. Review. _


Central nervous system (CNS) involvement by tumoral metastasis is a potentially life-threatening complication, representing the immediate cause of death in more than 50 percent of the cases. Of note, brain metastasis represents the most common brain tumor in the United States (US). The most common brain metastasizing tumors include primaries from the lungs, breast, colon, skin (melanoma), and kidney. Two-year and five-year survival rates of 8.1 percent and 2.4 percent are noted for those with intracranial metastasis across various tumor types. Moreover, it has been estimated that 10-40 percent of all patients with cancer will eventually develop brain metastasis. The lack of reporting of the extent of metastatic spread at the time of enrolment into studies and follow-up in advanced cancer patients (who might go onto develop intracranial metastasis later) might be the reason underlying the underdiagnosis of this disease entity. …



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