Oncometabolite D-2-hydroxyglutarate inhibits ALKBH DNA repair enzymes and sensitizes IDH mutant cells to alkylating agents. (2016). Neuro Oncol. (2012) reported the survival benefit of immunotherapy in patients with relapsed AO enrolled in the HGG-IMMUNO-2003 trial. Oligodendrogliomas Primary GBMs Alternative lengthening of telomeres (ALT)/ATRX Astrocytomas Secondary GBMs Cohesion between sister chromatids provides a template for recombination and repair during and after DNA replication in S and G 2phases of the cell cycle 11 Mutations of Selected Genes in Glioma Subtypes Clinicopathologic correlations in the oligodendroglioma. Low-grade oligodendroglioma responds to chemotherapy. doi: 10.1523/JNEUROSCI.0160-09.2009, Fujii, Y., Muragaki, Y., Maruyama, T., Nitta, M., Saito, T., Ikuta, S., et al. Other treatments may be needed after surgery. Dual-genotype astrocytoma/oligodendroglioma are very rare. 100, 22352241. This image reveals a calcified hypoattenuating lesion that is invading the corpus callosum. 0000276291 00000 n J. Clin. (2009). . Pathol. Neurosurgery. Hence, cellular proliferation and dysregulation of pro-apoptotic pathways ensues (Ruas and Peters, 1998). Especially, delineation of oligoastrocytomas from (more) pure astrocytic and oligodendroglial tumors is poorly reproducible. Advertising revenue supports our not-for-profit mission. Benifla, M., Otsubo, H., Ochi, A., Weiss, S. K., Donner, E. J., Shroff, M., et al. For patients with astrocytic tumors, EORTC26951 and RTOG9402 did not show any benefit of PCV with RT. Giannini, C.; Scheithauer, BW. Neuro Oncol. official website and that any information you provide is encrypted Seizures and the natural history of World Health Organization Grade II gliomas: a review. Int. Gliomas are tumors that arise from the glial, or supportive cells of the brain. [1] . Englot, D. J., Berger, M. S., Barbaro, N. M., and Chang, E. F. (2011). sharing sensitive information, make sure youre on a federal Oligodendroglioma is a growth of cells that starts in the brain. Oligodendroglial tumors are rare tumors that constitute part of the neuro epithelial tumors of the central nervous system. doi: 10.1200/JCO.2003.12.015, Vogelbaum, M. A., Berkey, B., Peereboom, D., Macdonald, D., Giannini, C., Suh, J. H., et al. Thus, prognostic markers should be assessed while accounting for other genetic alterations. doi: 10.1200/jco.1995.13.8.2066. Ino, Y., Betensky, R. A., Zlatescu, M. C., Sasaki, H., Macdonald, D. R., Stemmer-Rachamimov, A. O., et al. Elens et al. Overexpression of PDGF system components, particularly the subtype receptor (PDGFR), was detected in Southern and Fluorescence in situ hybridization (FISH) analyses 4/41 AO. doi: 10.1016/j.celrep.2015.11.029, Warnick, R. E., Prados, M. D., Mack, E. E., Chandler, K. L., Doz, F., Rabbitt, J. E., et al. Few calcifications are present. For example, a test may look at the changes in the tumor cells' genetic material, called DNA. TERT reactivation then takes place when GA-binding protein (GABP) transcription factor binds to the mutant TERT promoter (Dahlin et al., 2016). J. Biol. Clin. NCI CPTC Antibody Characterization Program, Agnihotri S, Aldape KD, Zadeh G. Isocitrate dehydrogenase status and molecular subclasses of glioma and glioblastoma. Upon surgical debulking and pathological diagnosis, he was found to have recurrent diseases. doi: 10.1242/dev.057729, Alattar, A. Their good prognosis relative to other parenchymal tumors probably stems from inherently less aggressive biological behavior and a favorable response to radiation and chemotherapy. [QxMD MEDLINE Link]. Commun. Oligodendroglioma - Libre Pathology Oligodendroglioma Oligodendroglioma, IDH mutant and 1p/19q codeleted is CNS tumour that is typically in the cerebral hemispheres. 7, 205207. Tests can show what types of cells are involved. BioMed Res. Int. Neurobiol. A., Tosoni, A., Cavallo, G., Reni, M., Franceschi, E., Bonaldi, L., et al. (2021). (2000b). What are the symptoms of oligodendrogliomas? J. Neurooncol. We Choose to Fight through Advocacy, Two-time Oligodendroglioma Survivor: Never Give Up Hope, NCI-CONNECT Rare Brain and Spine Tumor Network, U.S. Department of Health and Human Services. doi: 10.1212/wnl.46.1.203, Michaud, K., de Tayrac, M., DAstous, M., Paquet, C., Gould, P. V., and Saikali, S. (2018). Mason WP, DeAngelis LM. With approximately 108 participants included in this study, the estimated completion date is July 2022. To get an accurate diagnosis, a piece of tumor tissue will be removed during surgery, if possible. doi: 10.1007/s00401-016-1545-1, Lu, C., Ward, P., Kapoor, G., Rohle, D., Turcan, S., Abdel-Wahab, O., et al. J. Pathol. Postoperative radiotherapy (XRT) to a total dose of roughly 60 Gy over 30 fractions is recommended (Blakeley and Grossman, 2008). xref 110, 129135. Pitt MA, Jones AW, Reeve RS, Cowie RA. 0000004228 00000 n These cells make a substance that protects nerve cells and helps with the flow of electrical signals in the brain and spinal cord. 2020 May 15. To establish the diagnosis of AO, a pathological sample is crucial. (Aug 2013). Suzuki SO, Kitai R, Llena J, Lee SC, Goldman JE, Shafit-Zagardo B (May 2002). Patients in arm A received RT with concomitant TMZ followed by adjuvant TMZ. Elefante A, Peca C, Del Basso De Caro ML, Russo C, Formicola F, Mariniello G, et al. They occur primarily in adults (9.4% of all primary brain and central nervous system tumors) but are also found in children (4% of all primary brain tumors). Phase 2 study of weekly irinotecan in adults with recurrent malignant glioma: final report of NABTT 97-11. The majority of oligodendrogliomas occur in the frontal lobe, and the second most common site affected is the temporal lobe. With proper education, the patient and family can develop good insight into the course and prognosis of the tumor. This tumor, previously diagnosed as GBM-O, WHO grade IV featured mostly cells resembling astrocytoma (, Example where molecular reclassification does not affect tumor grade. What are the grades of oligodendrogliomas? (2009). Cairncross JG, Berkey B, Shaw E. Phase III trial of chemotherapy plus radiotherapy compared with radiotherapy alone for pure and mixed anaplastic oligodendrogliomas: intergroup Radiation Therapy Oncology Group Trial 9402. Daumas-Duport C, Scheithauer BW, Chodkiewicz JP, et al. A feature of oligodendroglioma that can be assessed on CT, as well as on MRI, is the typical location of the lesion. CDKN2/p16 or RB alterations occur in the majority of glioblastomas and are inversely correlated. doi: 10.1200/jco.1999.17.5.1516, Fu, H., Cai, J., Clevers, H., Fast, E., Gray, S., Greenberg, R., et al. Neurology 68, 18311836. Center for Cancer Research doi: 10.1371/journal.pone.0163067. (2012) showed that an IDH1 mutation can induce a methylation profile known as the G-CIMP signature, which is a glioma specific methylation pattern at CpG islands. Retrospective studies have clearly defined the most common presenting symptoms and tumor locations. Nature 483, 479483. Salvage chemotherapy with taxol for recurrent anaplastic astrocytomas. 1988 May 1. Amplification of the platelet-derived growth factor receptor-A (PDGFRA) gene occurs in oligodendrogliomas with grade IV anaplastic features. Prior to the WHO 2016 classification of CNS tumors, grades 2 and 3 gliomas were not molecularly distinguished by 1p/19q codeletion status. (Dec 2014). Note: If molecular testing fails, cases should be classified as Oligodendroglioma, NOS. 0000005528 00000 n This image reveals a well-demarcated, left frontal hypoattenuating lesion with a small calcification. (2017). Pekmezci, M., Rice, T., Molinaro, A. M., Walsh, K. M., Decker, P. A., Hansen, H., et al. (2017). Mayo Clinic College of Medicine and Science, Mayo Clinic Graduate School of Biomedical Sciences, Mayo Clinic School of Graduate Medical Education, Mayo Clinic School of Continuous Professional Development, Mayo Clinic on Incontinence - Mayo Clinic Press, NEW Mayo Clinic on High Blood Pressure - Mayo Clinic Press, Mayo Clinic on Hearing and Balance - Mayo Clinic Press, FREE Mayo Clinic Diet Assessment - Mayo Clinic Press, Mayo Clinic Health Letter - FREE book - Mayo Clinic Press, Financial Assistance Documents Minnesota, Infographic: Molecular Classification of Gliomas, Intraoperative magnetic resonance imaging (iMRI), Research provides critical information about the size and growth speed of gliomas, Book: Mayo Clinic Family Health Book, 5th Edition, Newsletter: Mayo Clinic Health Letter Digital Edition. 2003 Jul 1. Neuro Oncol. Accordingly, the treatment approach is tailored according to the presence of 1p19q co-deletion, which characterizes oligodendrogliomas. 24, 47464753. Consequently, and in terms of improvement in quality of life (QOL), the EORTC study showed no difference between the two groups, and PCV toxicity contributed to a decreased QOL for a prolonged period. Evidence from in vivo models have demonstrated reduced levels of STAT1 and CXCL10 in IDH-mutant gliomas. doi: 10.1016/s1470-2045(16)30122-x, Batchelor, T. T., Gilbert, M. R., Supko, J. G., Carson, K. A., Nabors, L. B., Grossman, S. A., et al. 21(13):2525-8. Symptoms include seizures, headaches, and weakness or disability in a certain part of the body. [QxMD MEDLINE Link]. Neuro Oncol. Oligodendroglioma: pathology, molecular mechanisms and markers For nearly a century, the diagnosis and grading of oligodendrogliomas and oligoastrocytomas has been based on histopathology alone. %%EOF Res. In addition to being a surrogate for oligodendroglial lineage, TERT mutations seem to have some prognostic significance (Dahlin et al., 2016). 2004 Jul 1. *Correspondence: Hazem I. Assi, ha157@aub.edu.lb, https://doi.org/10.3389/fnmol.2021.722396, Creative Commons Attribution License (CC BY), Division of Hematology and Oncology, Department of Internal Medicine, Naef K. Basile Cancer Institute, American University of Beirut Medical Center, Beirut, Lebanon. This in turn provides evidence that IDH mutations could allow cells to remain in a vulnerable state, and prone to additional DNA alterations. O, Rourke, DM; Berger, SL; Chan, TA; Levine, R. L.; Mellinghoff, IK; Thompson, CB IDH mutation impairs histone demethylation and results in a block to cell differentiation. 1998-2023 Mayo Foundation for Medical Education and Research (MFMER). Few neural tumours have round nuclei - DDx in intraoperative specimen: High mitotic rate (6 or more mitoses/10 HPF of 0.55mm). Kang SG, Kim JH, Nam do H, Park K. Clinical and radiological prognostic factors of anaplastic oligodendroglioma treated by combined therapy. Intravenous carboplatin for recurrent malignant glioma: a phase II study. Bethesda, MD 20894, Web Policies Maruno, M., Yoshimine, T., Muhammad, A. G., Tokiyoshi, K., and Hayakawa, T. (1996). The retinoblastoma protein and cell cycle control. Molecules 24:968. doi: 10.3390/molecules24050968, Killela, P. J., Reitman, Z. J., Jiao, Y., Bettegowda, C., Agrawal, N., and Diaz, L. A. Jr. et al. Nature 483, 484488. Contributed by Jared T. Ahrendsen, M.D., Ph.D. and John DeWitt, M.D., Ph.D. The interim report from the RTOG0131 trial suggests that combination therapy with TMZ and XRT is well tolerated in patients with AO being treated with neoadjuvant TMZ for 6 months, followed by TMZ and concurrent XRT (Tork and Atkinson, 2020). Brain, frontal lobe, left, tumor, resection. Correlations Between O6-Methylguanine DNA Methyltransferase Promoter Methylation Status, 1p and 19q Deletions, and Response to Temozolomide in Anaplastic and Recurrent Oligodendroglioma: A. J. Clin. Temozolomide treatment for newly diagnosed anaplastic oligodendrogliomas: a clinical efficacy trial. doi: 10.1101/gad.13.12.1501. WebPathology is a free educational resource with 12,142 high quality pathology images of benign and malignant neoplasms and related entities. [QxMD MEDLINE Link]. 0000245612 00000 n It can also stimulate the activity of EGLN leading to decreased HIF levels. 13, 15011512. Molecular subtypes of anaplastic oligodendroglioma: implications for patient management at diagnosis. Cerebral oligodendroglioma: prognostic factors and life history. The most common sign of an oligodendroglioma is a seizure. ; Stolt, CC. Pharm. Smith, J. S., Perry, A., Borell, T. J., Lee, H. K., OFallon, J., Hosek, S. M., et al. National Comprehensive Cancer Network. Caroline T Goldin, MD Fellow in Neuro-oncology, Department of Neurology, University of Colorado School of MedicineDisclosure: Nothing to disclose. New York: Oxford University Press; 2000. doi: 10.1200/JCO.1994.12.10.2013, Cairncross, G., Wang, M., Shaw, E., Jenkins, R., Brachman, D., Buckner, J., et al. Ueki, K., Ono, Y., Henson, J. W., Efird, J. T., von Deimling, A., and Louis, D. N. (1996). Accounting to up to 5% of all neuroepithelial tumors ( Ostrom et al., 2017 ), oligodendroglial tumors have an incidence rate of around 1,000 new cases per year in the United States. doi: 10.1002/path.2995, You, G., Sha, Z.-Y., Yan, W., Zhang, W., Wang, Y.-Z., Li, S.-W., et al. Labreche, K., Simeonova, I., Kamoun, A., Gleize, V., Chubb, D., Letouz, E., et al. Widespread dissemination in a gliomatosis cerebri fashion is very rare (DDx: Diffuse leptomeningeal glioneuronal tumour). Response rate and prognostic factors of recurrent oligodendroglioma treated with procarbazine, CCNU, and vincristine chemotherapy. The machine sends beams to exact points in your brain. ; Weaver, AL. 2002 Apr 15. 0000225404 00000 n J. Clin. Re-analysis of some trials prior to the 2016 WHO brain tumor classification has given further insight into some molecular pathways that were previously poorly defined or investigated. Oncol. Rodriguez, FJ. J. Clin. CODEL: phase III study of RT, RT+ TMZ, or TMZ for newly diagnosed 1p/19q codeleted oligodendroglioma. doi: 10.1007/s00401-012-0993-5, Sasaki, H., Zlatescu, M. C., Betensky, R. A., Ino, Y., Cairncross, J. G., and Louis, D. N. (2001). 19 (suppl_5):v1-v88. Oligodendroglioma,IDH mutant and 1p/19q codeleted. J. Neuropathol. IDH1 Arg-132 mutant promotes tumor formation through down-regulating p53. PLoS One 11:e0163067. Proc. A randomized clinical trial is currently in progress to compare the efficacy of PCV or TMZ when combined with RT in 1p19q co-deleted tumors (CODEL: NCT00887146). MRI: frontal lobe tumor with cystic change, Vote for your favorite image from the PathologyOutlines.com Directory. 23, 457467. J Pathol. 12,142 Images : Last Update : Apr 23, 2023. All rights reserved. Genes Dev. 0000144755 00000 n 10:2935. doi: 10.3389/fonc.2020.601452, Yung, W., Mechtler, L., and Gleason, M. J. [QxMD MEDLINE Link]. The HR was 3.12 with a 95% CI of 1.267.19 (P = 0.014) (Jaeckle et al., 2021). Subsequently, this codeletion appeared to not only carry diagnostic, but also prognostic and predictive information, the latter aspect only recently resolved after carefully constructed clinical trials with very long follow-up times. Pathophysiology Cell of origin is unknown, although the commonality of IDH mutation across IDH mutant astrocytoma and oligodendroglioma suggests a common histogenesis in these tumors; similarly, single cell sequencing of IDH mutant gliomas suggests this as well ( Acta Neuropathol 2009;118:469, Science 2017;355:eaai8478 ) Etiology (2016). Lancet Oncol. (2010). CORE - Aggregating the world's open access research papers 2016 Mar;18(3):388-400. doi: 10.1093/neuonc/nov182. Molecular pathways in gliomagenesis and their relevance to neuropathologic diagnosis. The median overall survival was 13.3 years in the RT+PCV group versus 7.8 years in the RT alone group, and progression-free survival at 10 years was 51% in the RT+PCV group versus 21% in the RT alone group. [QxMD MEDLINE Link]. (2011). (2009). 14, 230241. Oligodendrogliomas. In practice, (neuro)pathologists who readily accept the existence of mixed gliomas will more liberally diagnose oligoastrocytomas, while those who are skeptical that this entity exists will designate the vast majority of diffuse gliomas as either astrocytic or oligodendroglial (, Example of how molecular reclassification may affect tumor grade. Additionally, hypermethylation caused by IDH1 mutations was shown to occur at CTCF-binding sites that normally insulate and prevent the interaction between different parts of the genome (Flavahan et al., 2016). Investigators of this trial will be testing the in vitro sensitivity of individual primary tumors to anti-mir-10b treatment. This publication addresses two common gliomas: oligodendroglioma and oligoastrocytoma. J. Neurosurg. 6, 19. Concurrent inactivation of RB1 and TP53 pathways in anaplastic oligodendrogliomas. Molecular analysis of IDH1/2 hotspots and LOH1p/19q testing is required for diagnosis. Phase III trial of chemotherapy plus radiotherapy compared with radiotherapy alone for pure and mixed anaplastic oligodendroglioma: Intergroup Radiation Therapy Oncology Group Trial 9402. eCollection 2023 Apr. Focused Oligodendroglioma with stained slides of pathology. Phase II study of first-line chemotherapy with temozolomide in recurrent oligodendroglial tumors: the European Organization for Research and Treatment of Cancer Brain Tumor Group Study 26971. [QxMD MEDLINE Link]. Prognosis by flavours (average survival):[2]. (2012). There are 11 ongoing clinical trials recruiting patients with AO. Neurol Clin. The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous author Subramanian Hariharan, MD to the development and writing of this article. Oligodendroglial tumors. 56, 150153. doi: 10.1074/jbc.M111.258947, Louis, D., Perry, A., Reifenberger, G., von, D. A., Figarella-Branger, D., Cavenee, W. K., et al. This results in the opening of a binding site for the E26 transformation-specific transcription factors (Killela et al., 2013). Such tumors may be considered oligoastrocytomas. (2016). 2010, 279296. Adult infiltrating gliomas with WHO 2016 integrated diagnosis: additional prognostic roles of ATRX and TERT. Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug ReferenceDisclosure: Received salary from Medscape for employment. Oligodendroglioma, IDH-mutant and 1p/19q-codeleted, WHO CNS Grade 2 (ICD-O: 9450/3). (2016). ABM Salah Uddin, MD Private Practice, Norwood Neurology; Consulting Staff, Department of Neurology, St Vincent's Hospital (2018). -, Arita H, Narita Y, Fukushima S, Tateishi K, Matsushita Y, Yoshida A, Miyakita Y, Ohno M, Collins VP, Kawahara N, et al. 0000392498 00000 n Oligodendrogliomas. 7, 839845. Abrey, L. E., Childs, B. H., Paleologos, N., Kaminer, L., Rosenfeld, S., Salzman, D., et al. NCT04708548 is an ongoing European cross-sectional study that is looking at health-related quality of parameters and outcomes in survivors after being treated with surgery, chemotherapy and/or RT. Oligodendroglioma is a primary central nervous system (CNS) tumor. TCF12 is mutated in anaplastic oligodendroglioma. Burger PC, Rawlings CE, Cox EB, et al. [QxMD MEDLINE Link]. 55, 48334836. mTOR-dependent cell proliferation in the brain. Neurosurgeon Dr. Elizabeth Claus discusses her International Low Grade Glioma Registry, a study of the evolution of the low-grade glioma genome and the cells driving resistance to treatment. IDH mutated enzymes can promote proliferation and colony formation through its end metabolite 2-HG (Koivunen et al., 2012; Bittinger et al., 2013). (2003). Oligodendroglioma. van den Bent, M. J., Dubbink, H. J., Marie, Y., Brandes, A. Roldan G, Scott J, George D, Parney I, Easaw J, Cairncross G. Leptomeningeal disease from oligodendroglioma: clinical and molecular analysis. All oligodendroglial neoplasms and DNTs showed widespread OLIG2 expression. 2017 Nov 6. Your care team uses this information to create a treatment plan. 0000144292 00000 n This tumor exhibits oligodendroglial-type nuclei and scanty eosinophilic fibrillar cytoplasm amidst a mucinous background. Lancet. https://www.cancer.gov/types/brain/patient/adult-brain-treatment-pdq. 2022 Nov 22;15(3):e23. (2001) showed that 7/72 AO had PTEN gene alterations; 2 had homozygous DMBT1 deletions, but at least one reflected unmasking of a germline DMBT1 deletion. 0000002967 00000 n Am. Oligodendroglioma of the fourth ventricle with intracranial and spinal oligodendrogliomatosis: a case report. Several genetic and protein alterations have been identified in AO. This helps show the important parts of the brain so the surgeon can avoid them. Tambi Jarmi, MD is a member of the following medical societies: American College of Physicians, American Medical AssociationDisclosure: Nothing to disclose. Neurosci. Glioblastoma with oligodendroglioma component (GBM-O): molecular genetic and clinical characteristics. Yip S, Butterfield YS, Morozova O, Chittaranjan S, Blough MD, An J, Birol I, Chesnelong C, Chiu R, Chuah E, Corbett R, Docking R, Firme M, Hirst M, Jackman S, Karsan A, Li H, Louis DN, Maslova A, Moore R, Moradian A, Mungall KL, Perizzolo M, Qian J, Roldan G, Smith EE, Tamura-Wells J, Thiessen N, Varhol R, Weiss S, Wu W, Young S, Zhao Y, Mungall AJ, Jones SJ, Morin GB, Chan JA, Cairncross JG, Marra MA. 2013;23:454461. This website also contains material copyrighted by 3rd parties. In this review article, we describe the clinical management of AO and summarize the different molecular pathways that drive the development, maintenance, and treatment response of these tumors. Options Neurol. Oncol. J. Neurooncol. CIMP + and MGMT-STP27 methylated tumors had a clear benefit from adjuvant PCV; the median OS in the RT and RT-PCV arms was 3.27 vs. 9.51 years (P < 0.0033), respectively for CIMP + tumors and 1.98 vs. 8.65 years (P < 0.0001) for MGMT-STP27 methylated tumors (van den Bent et al., 2013b). [QxMD MEDLINE Link]. Doctors suspect that in some cases, a chromosome abnormality may be the cause. 0000017138 00000 n Seizure characteristics and control following resection in 332 patients with low-grade gliomas. Bettegowda, C. (2000). Shaw EG, Wang M, Coons SW, Brachman DG, Buckner JC, Stelzer KJ, et al. A brain tumor survivor shares his experience with oligodendroglioma and advice for others. Front. Neurol. Cancer Interdiscipl. van den Bent, M. J., Erdem-Eraslan, L., Idbaih, A., de Rooi, J., Eilers, P. H., Spliet, W. G., et al. Oligodendroglioma is considered the third most common glioma accounting for 2%-5% of primary brain tumors and 5%-18% of all glial neoplasms 8. Oligodendrogliomas. Adjuvant procarbazine, lomustine, and vincristine chemotherapy in newly diagnosed anaplastic oligodendroglioma: long-term follow-up of EORTC brain tumor group study 26951. It was shown by Uhm (2010) that IDH mutations lead to the acquisition of a new enzymatic function that catalyzes the formation of D-2HG from alpha-KG. Chem. 27, 332342. Cancer Cell 19, 1730. 366(9490):985-90. Results of this trial raise the possibility that the chemosensitivity seen in these tumors might be due to the IDH mutation that is common to both oligodendroglial and low-grade astrocytic gliomas. Schold SC, Burger PC, Minna JD, et al. (2017) studied the status of both TERT and ATRX mutations along with their prognostic values in cohorts including grade II/III astrocytomas. J. Neurosurg. Please enable it to take advantage of the complete set of features! A genome-wide screen for spatially restricted expression patterns identifies transcription factors that regulate glial development. (2016). (Jan 2015). The main function of the IDH1 and IDH2 enzymes is the oxidative decarboxylation of isocitrate to alpha-ketoglutarate. Neurol Sci. van den Bent MJ, Taphoorn MJ, Brandes AA, et al. %PDF-1.4 % Commun. Interim results from the CATNON trial (EORTC study 26053-22054) of treatment with concurrent and adjuvant temozolomide for 1p/19q non-co-deleted anaplastic glioma: a phase 3, randomised, open-label intergroup study. ken macdonald tigercat net worth, owlet low oxygen level false alarm, allison dine real photo,
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