In patients with astrocytic tumors, only PFS was prolonged in patients treated with XRT who received up-front PCV vs. PCV at the time of recurrence (Pan-Weisz, 2019; Tork and Atkinson, 2020). 374 (14):1344-55. Wiestler, B.; Capper, D.; Hovestadt, V.; Sill, M.; Jones, DT. Hence, cellular proliferation and dysregulation of pro-apoptotic pathways ensues (Ruas and Peters, 1998). (2016). Tork, C. A., and Atkinson, C. (2020). Curr. PCV and TMZ are also used in cases of recurrence but result in lower response rates and disease-free survival. Oligodendroglioma confers higher risk of radiation necrosis. Computed tomography scan of a low-grade oligodendroglioma. This trial aims to determine the maximum tolerated dose of ONC206. [QxMD MEDLINE Link]. [Full Text]. Please enable it to take advantage of the complete set of features! Neuro Oncol. 0000446831 00000 n Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher. (2019). Yu, G., Butler, M. K., Abdelmaksoud, A., Pang, Y., Su, Y.-T., Rae, Z., et al. In an ongoing phase 3 study (NCT00887146), patients with AO or low-grade gliomas were split into two arms. doi: 10.1038/nature10860, Luyken, C., Blmcke, I., Fimmers, R., Urbach, H., Elger, C. E., Wiestler, O. D., et al. Appropriate design of future clinical trials can help in determining better correlations with molecular subclasses. 19, (Suppl._5) v1v88. Cleveland Clinic Lerner College of Medicine, School of Medicine, Case Western Reserve University, United States, Department of Neurosurgery, School of Medicine, Tohoku University, Japan. What are the grades of oligodendrogliomas? ; Hernndez-Lan, A. et al. 0000277188 00000 n -, Appin CL, Gao J, Chisolm C, Torian M, Alexis D, Vincentelli C, Schniederjan MJ, Hadjipanayis C, Olson JJ, Hunter S, et al. CIC normally functions as a reversible repressor by binding to the DNA regulatory elements downstream of growth factor signaling pathways (Ajuria et al., 2011). 71-82. van den Bent MJ, Afra D, de Witte O, et al. Oncol. 2-HG can inhibit alpha-KG dependent dioxygenases and cause epigenetic alterations (Xu et al., 2011). J. Neurooncol. Oligodendrogliomas. 287, 27982809. (2013). 2005 Jun. The wildtype (WT) TERT group was associated with good prognosis only in IDH1/IDH2 WT (IDH-WT) grade II/III astrocytomas. Grade 3 tumors have a median age at diagnosis that is 510 years older than grade 2 tumors. Neuro Oncol. Few calcifications are present. Boston: Butterworth Heinemann; 1997. In a subgroup analysis, oligodendroglioma diagnosis was a favorable prognostic factor resulting in increased overall and progression-free survival; however, oligodendrogliomas were classified histologically in this study, not by 1p/19q status. This activation is of special interest since it has been shown that mTOR and its downstream effectors are implicated in tumorigeneses in brain malignancies (Fan and Weiss, 2010; Ryskalin et al., 2017). Brain, frontal lobe, left, tumor, resection. 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. Thus, prognostic markers should be assessed while accounting for other genetic alterations. Oligodendroglioma, IDH mutant and 1p/19q codeleted is CNS tumour that is typically in the cerebral hemispheres. (2003). Oligodendroglial tumors are rare tumors that constitute part of the neuro epithelial tumors of the central nervous system. Cancer Cell 19, 1730. 2012 Jan;226(1):7-16. doi: 10.1002/path.2995. (2013). J. Clin. Pang Y, Zhou S, Zumbo P, Betel D, Cisse B. Preliminary results are mentioned toward the end of the manuscript. B., Raizer, J. J., Mason, W., et al. 108, 227235. PLoS One 8:e68782. have a. Consider Glioblastoma with oligo features when tumor is IDH1/2 wildtype and has no LOH 1p/19q and no ATRX loss. Roger E McLendon, MD is a member of the following medical societies: American Association of Neuropathologists, College of American Pathologists, Society for Neuro-OncologyDisclosure: Nothing to disclose. This image shows monomorphous tumoral proliferation that consists of round, regular cells with a small, central, hyperchromatic nucleus surrounded by clear cytoplasm. IDH mutated enzymes can promote proliferation and colony formation through its end metabolite 2-HG (Koivunen et al., 2012; Bittinger et al., 2013). National Cancer Institute of Canada Clinical Trials Group. [QxMD MEDLINE Link]. 14:722396. doi: 10.3389/fnmol.2021.722396. 0000275965 00000 n Pharm. 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. Primary CNS tumors are graded based on the tumor location, tumor type, extent of tumor spread, genetic findings, the patients age, and tumor remaining after surgery, if surgery is possible. The end result is DNA hypermethylation and thus the blockage of cellular differentiation (Kaminska et al., 2019). A neuropathologist should then review the tumor tissue. Intraleptomeningeal growing tumour cells presented usually a very strong positivity. 13:861-873. Oligodendroglioma is a primary central nervous system (CNS) tumor. Two plausible hypotheses to explain treatment resistance in oligodendrogliomas exist. Progression-free and overall survival of low grade gliomas in high-risk patients was studied in the RTOG-9802 trial. (Dec 2014). Neurol. To establish the diagnosis of AO, a pathological sample is crucial. (2017) patients with anaplastic astrocytoma or anaplastic oligoastrocytoma but not AO had a significant survival advantage when resection of at least 53% of the preoperative T2-weighted high-signal intensity volume was done. Wick, W., Hartmann, C., Engel, C., Stoffels, M., Felsberg, J., Stockhammer, F., et al. This was attributed to the sensitivity of oligodendrogliomas to chemotherapy compared to astrocytomas (Alattar et al., 2018). Temporal lobe tumoral epilepsy: characteristics and predictors of surgical outcome. 0000144833 00000 n Temozolomide chemotherapy versus radiotherapy in high-risk low-grade glioma (EORTC 22033-26033): a randomised, open-label, phase 3 intergroup study. [QxMD MEDLINE Link]. 2016 Nov. 17 (11):1521-1532. (1998). 0000013354 00000 n The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. Alterations of chromosome arms 1p and 19q as predictors of survival in oligodendrogliomas, astrocytomas, and mixed oligoastrocytomas. Oligodendroglioma: pathology, molecular mechanisms and markers Pathology Outlines - Olig2 The median survival of all low-grade gliomas was estimated at 410 years, and survival of grade 3 gliomas was estimated at 34 years after diagnosis. Neurol Sci. Oligodendrogliomas have a fried egg appearance under the microscope with sheets of round nuclei surrounded by clear cytoplasm. They can rarely arise infratentorially or in the spinal cord. The chromatin appearance is finely threadlike to smudgy, often associated with pointlike basophilic chromocenters, rather than nucleoli. National Library of Medicine doi: 10.1097/00006123-199811000-00035, Taliansky-Aronov, A., Bokstein, F., Lavon, I., and Siegal, T. (2006). Polymorphous low-grade neuroepithelial tumor of the young - PubMed 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. Mason WP, DeAngelis LM. Englot, D. J., Berger, M. S., Barbaro, N. M., and Chang, E. F. (2011). Paleologos NA, Vick NA, Kachoris JP. [QxMD MEDLINE Link]. Neuro Oncol. doi: 10.1074/jbc.RA117.001385, Johnson, B. E., Mazor, T., Hong, C., Barnes, M., Aihara, K., McLean, C. Y., et al. Pathology and Genetics of Tumours of the Nervous System. government site. In order to avoid detection of false-positive cases with partial 1p and/or 19q loss, ideally a test is used that allows for analysis of multiple loci along each chromosome arm. All material on this website is protected by copyright, Copyright 1994-2023 by WebMD LLC. Major drugs utilized in the treatment of AO. 2005 Jul. 55, 48334836. 36:294-295. Daumas-Duport C, Scheithauer BW, Chodkiewicz JP, et al. Relation between established glioma risk variants and DNA methylation in the tumor. Oligodendroglioma | The Brain Tumour Charity 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). J. Clin. 7(4):305-314. During this type of surgery, you're awakened from a sleep-like state. 0000276911 00000 n Neurol Med Chir (Tokyo). 29, 1139911408. Lancet 390, 16451653. 21, 251255. doi: 10.1038/nature08617, Uittenbogaard, M., and Chiaramello, A. 79, 153157. The goal of surgery is to obtain tissue to determine the tumor type and to remove as much tumor as possible without causing more symptoms for the person. An estimated 11,757 people are living with this tumor in the United States. Phase III trial of chemoradiotherapy for anaplastic oligodendroglioma: long-term results of RTOG 9402. eCollection 2022. Rep. 20, 19. 0000127092 00000 n Although one survey showed that 34% of neuro-oncologists suggested delaying XRT in patients with 1p19 co-deletions (Abrey et al., 2007), clinical trials addressing the efficacy of delayed XRT in this subset of patients are needed. 13, 15011512. D-2-hydroxyglutaric acid induces oxidative stress in cerebral cortex of young rats. doi: 10.1200/jco.1999.17.5.1516, Fu, H., Cai, J., Clevers, H., Fast, E., Gray, S., Greenberg, R., et al. doi: 10.1126/science.1239947, Kaloshi, G., Benouaich-Amiel, A., Diakite, F., Taillibert, S., Lejeune, J., Laigle-Donadey, F., et al. [QxMD MEDLINE Link]. Radiation plus Procarbazine, CCNU, and Vincristine in Low-Grade Glioma. official website and that any information you provide is encrypted Oligodendrogliomas are primary brain tumours that are a type of glioma. Chan, A. 2004 Dec. 17(6):675-80. sharing sensitive information, make sure youre on a federal Lancet Oncol. Oligodendrogliomas are usually tumors of middle-aged adults, occurring most commonly in the 4 th and 5 th decades of life, somewhat older for grade 3 tumors 10,11. Diffuse gliomas histopathologically form a spectrum, both with regard to cell type (astrocytic, oligodendroglial, mixed) and malignancy grade. Han SR, Yoon SW, Yee GT, Choi CY, Lee DJ, Sohn MJ, et al. 0000005528 00000 n Packer RJ, Sutton LN, Rorke LB, et al. All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Concurrent inactivation of RB1 and TP53 pathways in anaplastic oligodendrogliomas. 0000276357 00000 n van den Bent, M. J., Erdem-Eraslan, L., Idbaih, A., de Rooi, J., Eilers, P. H., Spliet, W. G., et al. Curr. For nearly a century, the diagnosis and grading of oligodendrogliomas and oligoastrocytomas has been based on histopathology alone. IDH1 Arg-132 mutant promotes tumor formation through down-regulating p53. Int. What are the symptoms of oligodendrogliomas? ; Bauserman, S. et al. 10(13):4303-6. (2017). Oligodendroglioma Diagnosis and Treatment - NCI - National Cancer Institute Mutational analysis reveals the origin and therapy-driven evolution of recurrent glioma. (2014). Acta Neuropathol. (2008). Health-Related Quality of Life and Executive Functioning among Primary Brain Tumor Patients: Associations and Causal Pathways: University of California, San Diego; 2019. (1994). The RTOG 9802 trial, which included non-molecularly stratified patients harboring grade II gliomas, demonstrated a 5.5-year survival benefit of PCV administration (Shaw et al., 2008). 1995. (May 2019). J. Neurooncol. 19, 55135522. Weinberg, R. A. As expected, patients with an IDH mutation and 1p19q co-deletion showed significant benefit in OS. Options Neurol. 17:984. doi: 10.3390/ijms17060984. doi: 10.1227/neu.0b013e31820c3419, Soffietti, R., Rud, R., Bradac, G. B., and Schiffer, D. (1998). 31:337. doi: 10.1200/jco.2012.43.2674, Cairncross, J. G., Wang, M., Jenkins, R. B., Shaw, E. G., Giannini, C., Brachman, D. G., et al. 0000255421 00000 n 0000225381 00000 n Their predictive value stems from their close relationship to human gliomas. Other treatments may be recommended if the tumor can't be removed or if it's likely to come back after surgery. The growth of cells, called a tumor, begins in cells called oligodendrocytes. [QxMD MEDLINE Link]. Br J Neurosurg. Elens et al. Acting as a tumor-suppressor gene, missense mutations affecting CIC are mostly found within the DNA-binding domain thereby inhibiting its binding to regulatory elements. Table 1 outlines some information related to the major drugs used in treatment. This co-deletion, along with the IDH mutation, enables a tumor to be classified as an oligodendroglioma according to the WHO 2016 criteria (Louis et al., 2016). 32:783. doi: 10.1200/jco.2013.49.3726, Calatozzolo, C., Pollo, B., Botturi, A., Dinapoli, L., Carosi, M., Salmaggi, A., et al. The role of IDH2, on the other hand, is limited to the mitochondria where it catalyzes the same reaction as part of the tricarboxylic acid cycle (TCA). (Agios Pharmaceuticals, Cambridge, MA) Nature 462: 739-744, 2009. Oncol. Cancer Soc. 100, 22352241. Long-term efficacy of early versus delayed radiotherapy for low-grade astrocytoma and oligodendroglioma in adults: the EORTC 22845 randomised trial. Neurol Clin. 0000276833 00000 n Acta Neuropathol. doi: 10.1101/gad.13.12.1501. doi: 10.1215/s1152851703000218, Baumgarten, P., Harter, P., Tnjes, M., Capper, D., Blank, A. E., Sahm, F., et al. 2008 Apr 15. 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. Lancet. [4]. (2013) was the first to conduct a meta-analysis on PFS and OS in gliomas based on IDH mutations. Concurrent CIC mutations, IDH mutations, and 1p/19q loss distinguish oligodendrogliomas from other cancers. All in all, patients with 1p19q co-deleted tumors should be treated with RT and adjuvant PCV while those lacking this co-deletion should receive adjuvant TMZ. Year Book Neurol. Both types of alterations have been shown to drastically impact the ability of TCF12 to function as a transcription factor and interact with other bHLH proteins, eventually leading to mutant protein accumulation (Labreche et al., 2015). Doctors suspect that in some cases, a chromosome abnormality may be the cause. 0000245728 00000 n Upon reanalysis of RTOG 9802 after molecular classification, AO patients with IDH-mutated tumors actually showed a survival benefit when treated with PCV chemotherapy (Cairncross et al., 2014). Barbashina V, Salazar P, Holland EC, Rosenblum MK, Ladanyi M. Clin Cancer Res. ABM Salah Uddin, MD Private Practice, Norwood Neurology; Consulting Staff, Department of Neurology, St Vincent's Hospital Int. 0000018446 00000 n Eight of 10 central neurocytomas, all clear cell meningiomas and 8/10 clear cell ependymomas were negative for OLIG2. (2006). doi: 10.1212/01.wnl.0000079374.78589.1b, Zhao, S., Lin, Y., Xu, W., Jiang, W., Zha, Z., Wang, P., et al. [QxMD MEDLINE Link]. Abrey, L. E., Louis, D. N., Paleologos, N., Lassman, A. It can also stimulate the activity of EGLN leading to decreased HIF levels. Lastly, it is worth noting that there are approximately 230 other clinical trials which involve oligodendrogliomas but are not actively recruiting patients. Around 60% of people have a seizure before being diagnosed. Infiltration of these cells might have been perceived as the increased mass on MRI. Hartmann, C.; von Deimling, A. doi: 10.1002/path.2995, You, G., Sha, Z.-Y., Yan, W., Zhang, W., Wang, Y.-Z., Li, S.-W., et al. Cancer. Douglas E Ney, MD is a member of the following medical societies: American Academy of Neurology, American Society of Clinical Oncology, Society for Neuro-OncologyDisclosure: Nothing to disclose. 1994 Dec. 35(6):1018-34; discussion 1034-5. Oligodendroglioma resection: a Surveillance, Epidemiology, and End Results (SEER) analysis. Sci. (2007). Sci. The spinal cord is a long thin structure that sits in the spinal column at the back of the body. Temozolomide for low-grade gliomas: predictive impact of 1p/19q loss on response and outcome. Megyesi JF, Kachur E, Lee DH, et al. Benifla, M., Otsubo, H., Ochi, A., Weiss, S. K., Donner, E. J., Shroff, M., et al. You are being redirected to Lately, IDH 1 and 2, which are known to generate nicotinamide adenine dinucleotide phosphate (NADPH), have been heavily observed. Oligodendroglioma: pathology, molecular mechanisms and markers For nearly a century, the diagnosis and grading of oligodendrogliomas and oligoastrocytomas has been based on histopathology alone. Therefore, PTEN is a target of 10q loss, and PTEN alterations are associated with aggressive tumor phenotypes regardless of chemosensitivity (Sasaki et al., 2001). CDKN2/p16 or RB alterations occur in the majority of glioblastomas and are inversely correlated. 9, 314318. 2010, 111112. doi: 10.1111/j.1349-7006.2009.01308.x, Ostrom, Q. T., Gittleman, H., Liao, P., Vecchione-Koval, T., Wolinsky, Y., Kruchko, C., et al. Gittleman H, Sloan AE, Barnholtz-Sloan JS. 2013;126:267276. Survival outcome and prognostic factors in anaplastic oligodendroglioma: a single-institution study of 95 cases. Oncol. However, no results have proven enough benefit for treating patients with recurrent AO. Human telomerase reverse transcriptase (TERT) mutations have been found to be present in 77% of grades II and III oligodendrogliomas and 82% of tumors with 1p19q co-deletion (Koelsche et al., 2013). 0000230580 00000 n Leptomeningeal spread can occur rarely in late stages of the disease. 0 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. On magnetic resonance imaging, he was considered to have disease progression. The Far Upstream Element (FUSE) Binding Protein 1 (FUBP1) is known to regulate several cell cycle regulators such as MYC and p21. doi: 10.3171/2017.3.JNS162383, Fulton, D., Urtasun, R., and Forsyth, P. (1996). If you would like to reproduce some or all of this content, see Reuse of NCI Information for guidance about copyright and permissions. 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. 0000277542 00000 n Patients harboring co-deleted tumors can receive either PCV or TMZ. Nature 483, 484488. Pitt MA, Jones AW, Reeve RS, Cowie RA. J. Pathol. [QxMD MEDLINE Link]. The PFS HR was 3.33 with a 95% CI 1.318.45 (P = 0.011) while the OS HR was 2.78 with a 95% CI 0.5813.22 (P = 0.20) (Jaeckle et al., 2021).