Received: 8 July 2022 Accepted: 8 July 2022 DOI: 10.1111/jvim.16488 LETTER TO THE EDITOR Response to letter regarding “Clinical features, diagnosis, and survival analysis of dogs with glioma” Dear Editor, of the lesion thereby limiting the value of their observations. Simi- Thank you for the opportunity to respond to the letter from larly, the subsequent studies Rohrer Bley and colleagues Drs Rohrer Bley, Meier, Beckmann, and Steffen regarding our paper in referenced to reiterate the superiority of radiotherapy over sur- JVIM titled “Clinical features, diagnosis, and survival analysis of dogs gery in the treatment of intracranial gliomas, lacked histologic with glioma.” We appreciate their interest in our study especially with confirmation for any of the masses treated. Those studies included regard to the discussion of our findings on treatment and survival in cases “suspected” of having intracranial glioma based on MRI char- our group of dogs with histologically confirmed glioma. acteristics; however, other tumor types or intraaxial brain lesions The aims of our study were to further characterize the clinico- such as cerebrovascular accidents or granulomas can mimic glio- pathologic and diagnostic imaging features of a large cohort of dogs mas on MRI.3,4 Potential inclusion of these can bias results toward with glioma as well as analyzing survival in those which received any more favorable outcomes. Thus, liberally comparing outcomes and type of therapy. We are happy to see that there were no concerns survival after radiotherapy in dogs with unconfirmed glioma with with our observations on the clinicopathologic and imaging features surgery in histologically confirmed cases5 is not accurate and could of the cases included. We were able to study survival in 45 of the mislead readers. included dogs, the largest cohort with histopathologic diagnosis of gli- To avoid that source of bias, we only included dogs with histopath- oma that we are aware of reported to date. Despite limitations, this ologically confirmed glioma in our analysis. Radiotherapy is routinely was of particular relevance as available information on treatment and offered as a therapeutic option for dogs with suspected glioma in all the outcome of dogs with histologically confirmed diagnosis of glioma institutions contributing to our study, either alone or in combination treated with any modality was anecdotal until our publication. Most with surgery for diagnosis and tumor debulking to alleviate clinical signs. importantly, we defined survival in a relatively large group of dogs Unfortunately, only 2 dogs treated with radiotherapy alone or in combi- receiving palliative therapies (ie, corticosteroids, antiepileptic, or anal- nation with surgery met our inclusion criterion. Radiation therapy spe- gesic medications as sole therapeutic intervention), which informs cifics were not provided due to this and the restrictions to manuscript future studies evaluating responses to other conventional or experi- extension. Dogs receiving chemotherapy in our study did so as their mental therapies. For analysis purposes and due to the limitations owners declined radiotherapy and surgery but elected this option in imposed by case numbers, we grouped dogs receiving surgery, radio- addition to palliative therapy either by enrolling in a clinical trial or therapy or chemotherapy in any combination together, similarly to a administering lomustine or temozolomide. Lomustine treatment was recent study of histiocytic sarcoma affecting the CNS.1 We would associated with longer survival than palliative therapy in dogs with pre- have preferred to refer to this group as receiving “specific” treatment sumptive intracranial glioma in a recent study albeit most of the included modalities; however, we were invited to use “definitive” treatment cases lacked histopathologic diagnosis,6 and temozolomide is a instead by the reviewers to, although admittedly not ideal, stay in line standard-of-care for adjuvant and monotherapy of high-grade gliomas in with the aforementioned publication.1 The term “definite treatment” humans and its use is being actively investigated in dogs.7 Finally, dogs used in our paper did not refer to the efficacy of the chosen treatment in our study that received cytarabine were suspected to have a nonin- modality but to the fact to treat a confirmed neoplasia by a presumed fectious granuloma based on MRI. antineoplastic therapy. Limitations of our survival analysis, mostly related to its Rohrer Bley and colleagues referred to a systematic review on retrospective nature, low case numbers and marked variability in brain tumor treatment in dogs to suggest that radiotherapy might treatment modalities, are well stated in the paper to assist with be more effective than surgery at treating intracranial tumors in interpretation of results. It was never inferred in the paper that any of dogs and that chemotherapy is not an acceptable option for such the more specific treatment modalities is superior to others, instead, purpose.2 However, that review failed to show a clear difference suggestion was made that specific therapies in general provide in outcome between radiotherapy and surgery. Furthermore, most a survival benefit to dogs with confirmed intracranial gliomas in of the studies evaluated in that review lacked histologic diagnosis comparison to palliative treatment. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2022 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC. on behalf of the American College of Veterinary Internal Medicine. 1568 wileyonlinelibrary.com/journal/jvim J Vet Intern Med. 2022;36:1568–1569. LETTER TO THE EDITOR 1569 With regards to the concerns risen about recommendations for Dolors Pi Castro6 euthanasia, presumptive diagnosis of glioma at any of the institutions Daniel Sánchez-Masian7 contributing to our paper was always followed by a thorough discus- Francisco Fernández-Flores8 sion with the owners regarding most likely diagnoses, their respective Katia Marioni-Henry9 prognosis, and treatment options including the abovementioned spe- Lara A. Matiasek10 cific therapeutic modalities and palliative treatment. Minimally inva- Kaspar Matiasek11 sive techniques (including stereotactic brain biopsies) to obtain a Emanuele Ricci12 definitive diagnosis and a maximally informed approach to treatment 1 are also offered to owners at the contributing institutions. Despite the Hamilton Specialist Referrals—IVC Evidensia, High Wycombe, available options, many owners still elected to euthanize in view of United Kingdom 2 the likely poor prognosis and the severity of the clinical status of some School of Veterinary Medicine, College of Medical, Veterinary and Life dogs, or due to financial constraints. Owner decision to euthanize is a Sciences, University of Glasgow, Glasgow, United Kingdom 3 common issue in veterinary medicine and, as stated in the paper, a Department of Animal Medicine and Surgery, Veterinary Faculty, limitation to analysis of glioma behavior in the light of treatment. Universitat Autònoma de Barcelona, Barcelona, Spain 4 Finally, another aim of our study was to assess the relationship TEAGASC, The Irish Food and Agriculture Authority, Cork, Ireland 5 between clinicopathologic features and survival and glioma histologic Anicura ARS Veterinaria, Barcelona, Spain 6 type and grade, based on the Comparative Brain Tumor Consortium Anicura Arvivet Hospital Veterinari, Barcelona, Spain 7 diagnostic classification. Tumor volume determined via MRI was nei- Hospital de Referencia Veterios, Madrid, Spain 8 ther associated with nor predictive of outcome in a recent study Uranovet, Barcelona, Spain 9 including 60 dogs with histologically confirmed glioma, thus, it was Royal (Dick) School of Veterinary Studies and Roslin Institute, University not included in our analysis.5 of Edinburgh, Edinburgh, United Kingdom 10 We failed to identify associations between survival and glioma Frontier Veterinary Specialists, Hergolding, Germany 11 type or grade. As acknowledged in our discussion, this could be related Centre for Clinical Veterinary Medicine, Ludwig-Maximilians- to the low number of cases (36) receiving any treatment, surviving Universitaet Muenchen, Munich, Germany 12 >1 day after imaging diagnosis, and with MRI available for revision Department of Veterinary Anatomy, Physiology and Pathology, included in our multivariable analysis of prognostic factors affecting University of Liverpool, Neston, United Kingdom survival. Again, marked variability in treatment modalities might have also influenced. By contrast, a subsequently published study including RE FE RE NCE S 33 gliomas, all treated with surgical resection and immunotherapy, 1. Toyoda I, Vernau W, Sturges BK, et al. Clinicopathological characteris- identified astrocytomas and low-grade tumors were associated with tics of histiocytic sarcoma affecting the central nervous system in dogs. J Vet Intern Med. 2020;34:828-837. increased survival.8 Whereas the latter study findings result from 2. Hu H, Barker A, Harcourt-Brown T, Jeffery N. Systematic review of univariable analysis ours resulted from univariable followed by multi- brain tumor treatment in dogs. J Vet Intern Med. 2015;29:1456-1463. variable Cox proportional hazard modeling. Therefore, differences 3. Cervera V, Mai W, Vite CH, Johnson V, Dayrell-Hart B, Seiler GS. between both studies' findings might be attributable to methodology Comparative magnetic resonance imaging findings between gliomas and presumed cerebrovascular accidents in dogs. Vet Radiol Ultrasound. of statistical analysis and lack of homogeneity of treatment modalities. 2011;52(1):33-40. Further evidence based on larger case numbers and multivariable 4. Diangelo L, Cohen-Gadol A, Heng HG, et al. Glioma mimics: magnetic statistical analysis is necessary to confirm any association between resonance imaging characteristics of granulomas in dogs. Front Vet Sci. glioma type or grade and prognosis in dogs. Thus, we take this oppor- 2019;6:286. 5. MacLellan JD, Arnold SA, Dave AC, et al. Association of magnetic tunity once again to invite researchers to contribute to the creation of resonance imaging-based preoperative tumor volume with postsurgical a mutually accessible international multicenter database to better survival time in dogs with primary intracranial glioma. J Am Vet Med enable evidence-based research in the field of canine glioma. Assoc. 2018;252:98-102. 6. Moirano SJ, Dewey CW, Wright KZ, Cohen PW. Survival times in dogs  pez1 Roberto José-Lo with presumptive intracranial gliomas treated with oral lomustine: a comparative retrospective study (2008-2017). Vet Comp Oncol. 2018; Rodrigo Gutierrez-Quintana2 16:459-466. Martí Pumarola3 7. Strupp R, Hegi ME, Mason WP, et al. Effects of radiotherapy with Cristian de la Fuente3 concomitant and adjuvant temozolomide versus radiotherapy alone on Sonia Añor3 survival in glioblastoma in a randomized phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol. 2009;10:459-466. Edgar G. Manzanilla4 8. Merickel JL, Pluhar GE, Rendahl A, O'Sullivan MG. Prognostic histopath- Anna Suñol5 ologic features of canine glial tumors. Vet Pathol. 2021;58(5):945-951.