Diffuse astrocytic tumor and oligodendroglial tumor [Neurosurgery Wiki]

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====== Diffuse astrocytic tumor and oligodendroglial tumor ======

The term “[[glioma]]” could technically be used to refer to all [[tumor]]s of any [[glia]]l lineage (i.e., from [[glial cell]]s such as [[oligodendroglia]], [[ependymal cell]]s, [[Schwann cell]]s, [[microglia]]...), but in its common usage, “glioma” usually refers only to [[astrocytic tumor]]s.
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According to the [[World Health Organization Classification of Tumors of the Central Nervous System 2016]] [[diffuse astrocytic tumor]] and [[oligodendroglial]] [[tumor]]s are differentiated by the presence of [[isocitrate dehydrogenase]] 1 or 2 (IDH1/2) mutation and the combined loss of the short arm of [[chromosome 1]] and the long arm of [[chromosome 19]] ([[1p/19q co-deletion]]). [[Diffuse astrocytoma IDH mutant]] often has [[p53]] and alpha-thalassemia/mental retardation syndrome X-linked ([[ATRX]]) mutation, showing the [[alternative lengthening of telomeres]] (ALT) [[phenotype]], while [[Oligodendroglioma, IDH-mutant & 1p/19q-codeleted]] often have wild-type p53 and telomerase reverse transcriptase ([[TERT]]) promoter mutation, showing [[telomerase activation]]. Ohba et al. analyzed IDH, ATRX, and TERT promoter mutations, and the correlation between them. Immortalized cells overcome the telomere-related crisis by activating telomerase or ALT. In glioma, telomerase is mainly activated by TERT promoter mutation, while [[ALT]] is usually associated with [[ATRX]] mutation. Although the mechanism of how [[ATRX]] mutation induces [[ALT]] remains unclear, ATRX loss alone is believed to be insufficient to induce ALT. Treatments targeting telomere maintenance are promising
((Ohba S, Kuwahara K, Yamada S, Abe M, Hirose Y. Correlation between IDH, ATRX, 
and TERT promoter mutations in glioma. Brain Tumor Pathol. 2020 Mar 29. doi:
10.1007/s10014-020-00360-4. [Epub ahead of print] Review. PubMed PMID: 32227259.
)).

===== Classification =====

see [[Diffuse astrocytic tumor and oligodendroglial tumor classification]].

===== Treatment =====

Adults with newly diagnosed [[oligodendroglioma]], [[IDH mutant]], [[1p/19q co-deletion]] CNS [[WHO grade II]] and [[WHO grade III]] should be offered [[radiation therapy]] (RT) and [[procarbazine]], [[lomustine]], and [[vincristine]] (PCV). [[Temozolomide]] (TMZ) is a reasonable alternative for patients who may not tolerate [[PCV]], but no high-level evidence supports upfront TMZ in this setting. People with newly diagnosed [[astrocytoma]], [[IDH-mutant]], non [[1p/19q co-deletion]] CNS [[WHO grade II]] should be offered [[RT]] with [[adjuvant]] [[chemotherapy]] ([[TMZ]] or [[PCV]]). People with astrocytoma, [[IDH mutant]], non [[1p/19q co-deletion]] CNS [[WHO grade III]] should be offered [[RT]] and adjuvant [[TMZ]]. People with astrocytoma, [[IDH mutant]], CNS [[WHO grade IV]] may follow [[recommendation]]s for either [[astrocytoma]], [[IDH mutant]], non [[1p/19q co-deletion]] CNS [[WHO grade III]] or [[glioblastoma]], [[IDH-wildtype]], CNS [[WHO grade IV]]. Concurrent [[TMZ]] and [[RT]] should be offered to patients with newly diagnosed [[glioblastoma]], IDH-wildtype, CNS WHO grade 4 followed by 6 months of adjuvant TMZ. Alternating electric field therapy, approved by the US Food and Drug Administration, should be considered for these patients. [[Bevacizumab]] is not recommended. In situations in which the benefits of 6-week RT plus TMZ may not outweigh the harms, hypofractionated RT plus TMZ is reasonable. In patients age ≥ 60 to ≥ 70 years, with poor performance status or for whom toxicity or prognosis are concerns, best supportive care alone, RT alone (for MGMT promoter unmethylated tumors), or TMZ alone (for MGMT promoter methylated tumors) are reasonable treatment options. Additional information is available at www.asco.org/neurooncology-guidelines
((Mohile NA, Messersmith H, Gatson NT, Hottinger AF, Lassman A, Morton J, Ney D, Nghiemphu PL, Olar A, Olson J, Perry J, Portnow J, Schiff D, Shannon A, Shih HA, Strowd R, van den Bent M, Ziu M, Blakeley J. Therapy for Diffuse Astrocytic and Oligodendroglial Tumors in Adults: ASCO-SNO Guideline. J Clin Oncol. 2022 Feb 1;40(4):403-426. doi: 10.1200/JCO.21.02036. Epub 2021 Dec 13. PMID: 34898238.)).