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Striking a Chord? Not a Typical Low-Grade Glioma

David M. McDermott, MD, and Sarah A. Singh, MD Department of Radiation Oncology, West Virginia University, Morgantown, West Virginia

A 48-year-old male presented with worsening gait instability, blurry vision, headache, and intermittent emesis over a 4-month period. Magnetic resonance imaging of the brain demonstrated a right ventricular mass at the foramen of Monro with associated obstructive hydrocephalus (Fig 1). The lesion was well circumscribed and nonenhancing and measured 1.9 cm  1.9 cm  2.1 cm with minimal surrounding edema. A computed tomography scan of the chest/abdomen/pelvis showed no evidence of extracranial disease. The patient underwent a right frontal transcortial transventricular approach for tumor resection and had external ventricular drain placement. Pathology demonstrated a chordoid glioma, World Health Organi- zation grade 2, Ki-67 index 3%, IDH1 wild-type, 1p/19q noncodeleted, MGMT-unmethylated, and absence of necrosis. Cerebrospinal fluid analysis was unremarkable. Postoperative magnetic resonance imaging obtained 24 hours after resection demonstrated gross total resection of the tumor and resolution of the hydrocephalus (Fig 2). The external ventricular drain was removed on postoperative day 6 with resolution of neurologic symptoms and a return to an excellent performance status.

Fig 1. Magnetic resonance imaging with contrast showing a 2.1-cm mass within the right foramen of Monro causing obstructive hydrocephalus as seen on T1-weighted axial (left), fluid-attenuated inversion recovery (middle), and T1-weighted sagittal (right) imaging.

Int J Radiation Oncol Biol Phys, Vol. 108, No. 3, pp. 518–519, 2020 0360-3016/$ - see front matter Ó 2019 Elsevier Inc. All rights reserved. https://doi.org/10.1016/j.ijrobp.2019.05.036 Volume 108  Number 3  2020 Gray Zones 519

Fig 2. Postoperative magnetic resonance imaging with contrast as seen on T1-weighted axial (left), fluid-attenuated inversion recovery (middle), and T1-weighted sagittal (right) imaging.

Questions 1. Can we extrapolate data from randomized controlled trials of conventional World Health Organization grade 2 glioma to chordoid glioma? 2. Would you consider adjuvant therapy or observation, and would this change for a subtotal resection? 3. If adjuvant therapy is an option, would you recommend radiation alone; radiation and procarbazine, lomustine, and vincristine; or radiation and Temodar?

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NotedCME is available for this feature as an ASTRO member benefit, to access visit https://academy.astro.org. Corresponding author: David M. McDermott, MD; E-mail: [email protected] Disclosures: David McDermott and Sarah Singh declare that they have no conflict of interest. www.redjournal.org

GRAY ZONE EXPERT OPINIONS

Typically, We Would Observe John H. Suh, MD Cleveland Clinic Chordoid glioma, a World Health Organization grade 2 Taussig Cancer Institute glioma, originates within the intraventricular system and is Department of Radiation Oncology characterized by its slow growth. Because it displays Cleveland, Ohio histopathologic/genetic features distinct from those of other Rose Ella Burkhardt Tumor and Neuro-Oncology Center low-grade gliomas,1 it is not representative of other Cleveland, Ohio low-grade gliomas reviewed in major randomized clinical Disclosures: Neither author has a conflict of interest. trials. Molecularly, it has recently been defined by PRKCA D463H gene mutation with lack of gene alterations in IDH1, IDH2, TP53, ATRX, TERT, MGMT, and 1p19q, and it lacks TSC1 or TSC2 alterations typical of subependymal References giant cell astrocytomas.2 Consequently, we would not extrapolate previous trial data to chordoid gliomas. 1. McDermott DM, Singh SA. Striking a Chord? Not a Typical Low- Recurrences after gross total resection (GTR) of chordoid Grade Glioma. Int J Radiat Oncol Biol Phys 2020;108:518-519. gliomas are uncommon with no clear benefit to radiation 2. Goode B, Mondal G, Hyun M, et al. A recurrent kinase domain therapy in this setting.3 Therefore, we would recommend mutation in PRKCA defines chordoid glioma of the third ventricle. close observation with serial magnetic resonance imaging Nat Commun 2018;9:810. 3. Liu WP, Cheng JX, Yi XC, et al. Chordoid glioma: A case report and after GTR. However, it is important to note that the literature review. Neurologist 2011;17:52-56. morbidity and mortality of GTR has been reported as high as 67% and 29%, respectively.3 After subtotal resection we would consider adjuvant stereotactic radiosurgery or https://doi.org/10.1016/j.ijrobp.2019.07.020 radiation therapy, particularly if residual tumor is adjacent to critical structures that could be adversely affected by tumor progression (eg, optic nerve/chiasm and hypothala- mus). If residual tumor is not adjacent to critical structures, Unique Glioma Requiring Unique observation with close follow-up magnetic resonance im- Management aging to assess rate of progression is recommended, although dose and fractionation may vary based on treatment adjuvantly or time of recurrence. Lastly, owing to The authors present a clinical case of a 48-year-old man chordoid glioma’s distinct genetics and lack of data to who had a gross total resection of a chordoid glioma (CG), support the use of chemotherapy, we would recommend World Health Organization (WHO) grade 2, Ki-67 index 1 radiation alone if adjuvant therapy is warranted. 3%. Although classified as a WHO grade 2 neuroepithelial tumor, CGs, unlike conventional WHO grade 2 gliomas, are Jonathan M. Sharrett, DO noninfiltrative and histologically consist of clusters and Cleveland Clinic cords of epithelioid tumor cells within a mucinous stroma Taussig Cancer Institute that commonly contains lymphoplasmacytic infiltrate. Department of Radiation Oncology Extent of surgery has been the only intervention factor Cleveland, Ohio consistently associated with outcome. However, aggressive

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. Int J Radiation Oncol Biol Phys, Vol. 108, No. 3, pp. 520–521, 2020 0360-3016/$ - see front matter Ó 2019 Published by Elsevier Inc. Volume 108  Number 3  2020 Gray Zone Expert Opinions 521 surgical resection for CG is associated with high risks of Chordoid gliomas belong to a different group of glioma complications owing to their location and proximity to than diffuse infiltrating glioma. In the new 2016 World various critical structures. Health Organization Classification of Tumors of the Central After gross total resection, as demonstrated in this case, Nervous System, they are listed under other gliomas.2 They the addition of adjuvant radiation therapy (RT) has not are mostly seen in the third ventricle, but there are also demonstrated improved tumor control. After subtotal cases described supratentorially. Recently, a new genetic resection or biopsy, both conventionally fractionated RT signature in the form of a PRKCA mutation different from with doses ranging from 50 to 60 Gy in 1.8 to 2 Gy frac- a typical diffuse glioma has been described,3 which can be tions and radiosurgery with doses ranging from 10 to 20 Gy of further diagnostic information if necessary. have demonstrated general safety.2 Although there is very In the literature, only very few cases have been limited data, the tumor control appears somewhat more described, without long-term follow-up provided.4 Adju- promising after radiosurgery than after conventionally vant postoperative radiation therapy is proposed in cases in fractionated RT. There is no convincing data to date to which no gross total resection could be achieved to gain suggest benefit from any chemotherapy, but a recent pub- local control of residual tumor. No data for adjuvant lication describes the discovery of a recurrent D463H chemotherapy are available. missense mutation in PRKCA in 13 of 13 GCs, which may Supratentorial chordoid gliomas may have been serve as a therapeutic target in the future.3 With this very included in earlier randomized trials for patients with low- rare tumor, coordinated efforts to pursue investigation grade gliomas. These trials were conducted before the use around multimodal therapy approaches are needed. of the new World Health Organization classification. A subgroup analysis for these tumors is not available. Caroline Chung, MD, MSc, FRPCPC, CIP Based on the details that the tumor has a low prolifer- Radiation Oncology and Diagnostic Radiology ation index, no postoperative residual tumor has been The University of Texas MD Anderson Cancer Center demonstrated, neurologic symptoms completely resolved, Houston, Texas and no trial data or sufficient clinical data available, I propose regular follow-up with imaging without adjuvant Disclosures: none. treatment. In case of a local relapse, local (eg, stereotactic) radiation therapy can be discussed.

References Brigitta G. Baumert, MD, PhD, MBA Institute of Radiation-Oncology Cantonal Hospital Graubu¨nden 1. McDermott DM, Singh SA. Striking a Chord? Not a Typical Low- Chur, Switzerland Grade Glioma. Int J Radiat Oncol Biol Phys 2020;108:518-519. 2. Ampie L, Choy W, Lamano JB, et al. Prognostic factors for recurrence Disclosures: none. and complications in the surgical management of primary chordoid gliomas: A systematic review of literature. Clin Neurol Neurosurg 2015;138:129-136. References 3. Goode B, Mondal G, Hyun M, et al. A recurrent kinase domain mu- tation in PRKCA defines chordoid glioma of the third ventricle. Nat Commun 2018;9:810. 1. McDermott DM, Singh SA. Striking a Chord? Not a Typical Low- Grade Glioma. Int J Radiat Oncol Biol Phys 2020;108:518-519. 2. Louis DN, Perry A, Reifenberger G, et al. The 2016 World Health Organization classification of tumors of the central nervous system: A https://doi.org/10.1016/j.ijrobp.2019.09.021 summary. Acta Neuropathol 2016;131:803-820. 3. Lucas CHG, Solomon DA, Perry A. A review of recently described genetic alterations in central nervous system tumors [e-pub ahead of print]. Hum Pathol. https://doi.org/10.1016/j.humpath.2019.10.009. Accessed November 27, 2019. Radiation for Relapse 4. Vanhauwaert DJ, Clement F, Van Dorpe J, et al. Chordoid glioma of the third ventricle. Acta Neurochir (Wien) 2008;150:1183-1191. This patient had a chordoid glioma at the right ventricle.1 He underwent gross total resection. Neurologic symptoms completely resolved after surgery. A low proliferation index with a Ki-67 of 3% was reported. https://doi.org/10.1016/j.ijrobp.2020.01.036

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