INTRODUCTION: Pediatric low-grade gliomas arising from the thalamus or thalamopeduncular junction are rare. Prognostic factors are thus seldom reported in the literature. RESEARCH QUESTION: This systematic review aims to define the factors influencing the prognosis of pediatric patients with thalamic and thalamopeduncular low-grade gliomas. MATERIAL AND METHODS: An extensive literature search in adherence to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was performed and included Web of Science, Scopus, and OVID interface (Medline and Embase). Original articles were selected if they provided data on 10 or more patients under 18 years old with separate or retrievable data for thalamic or thalamopeduncular low-grade gliomas, as well as at least one prognostic factor and its corresponding outcome. The risk of bias and applicability were assessed using The Quality Assessment of Prognostic Accuracy Studies criteria. RESULTS: The study selection process resulted in the inclusion of 14 articles out of the initial pool of 876 references. These 14 articles encompassed data from 446 patients. The prognostic factors reported were the extent of resection in ten studies, age and radiotherapy in four studies, bilateral involvement and molecular genetics in two studies, and sex and dissemination in one study each. Significant prognostic factors included the extent of resection, bilateral involvement, histology, and radiotherapy. DISCUSSION AND CONCLUSION: The reported factors considered significant for prognosis align with previously published data. The maximal safe resection, as a potentially curative modality for thalamic low-grade glioma, and the multidisciplinary approach to each patient should be a standard of care. Given the excellent long-term outlook of these patients, the extent of resection should not be pursued at the risk of neurological function since additional therapeutic possibilities are available today, such as molecular-targeted agents.

Center for Pediatric Neuro oncology Motol University Hospital Prague Czech Republic

Department of Neurosurgery 2nd Faculty of Medicine Charles University and Motol University Hospital Prague Czech Republic

Department of Neurosurgery and Neurooncology 1st Faculty of Medicine Charles University and Military Hospital Prague Czech Republic

Department of Paediatric Haematology and Oncology 2nd Faculty of Medicine Charles University and Motol University Hospital Prague Czech Republic

Institute of Scientific Information 1st Faculty of Medicine Charles University Prague Czech Republic

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Abrigo J.M., Fountain D.M., Provenzale J.M., Law E.K., Kwong J.S., Hart M.G., Tam W.W.S. Magnetic resonance perfusion for differentiating low-grade from high-grade gliomas at first presentation. Cochrane Database Syst. Rev. 2018;1:CD011551. doi: 10.1002/14651858.CD011551.pub2. PubMed DOI PMC

Bandopadhayay P., Bergthold G., London W.B., Goumnerova L.C., Morales La Madrid A., Marcus K.J., Guo D., Ullrich N.J., Robison N.J., Chi S.N., Beroukhim R., Kieran M.W., Manley P.E. Long-term outcome of 4,040 children diagnosed with pediatric low-grade gliomas: an analysis of the Surveillance Epidemiology and End Results (SEER) database. Pediatr. Blood Cancer. 2014;61:1173–1179. doi: 10.1002/pbc.24958. PubMed DOI PMC

Baro V., Sartori L., Caliri S.L., Furlanis G.M., D'Amico A., Meneghini G., Facchini S., Ferreri F., Corbetta M., Denaro L., Landi A. Navigated transcranial magnetic stimulation motor mapping and diffusion tensor imaging tractography for diencephalic tumor in pediatric patients. Brain Sci. 2023;13 doi: 10.3390/brainsci13020234. PubMed DOI PMC

Benes V., 3rd, Zapotocky M., Liby P., Taborsky J., Blazkova J., Jr., Blazkova J., Sr., Sumerauer D., Misove A., Pernikova I., Kyncl M., Krskova L., Koblizek M., Zamecnik J., Bradac O., Tichy M. Survival and functional outcomes in paediatric thalamic and thalamopeduncular low grade gliomas. Acta Neurochir. 2022;164:1459–1472. doi: 10.1007/s00701-021-05106-5. PubMed DOI

Bernstein M., Hoffman H.J., Halliday W.C., Hendrick E.B., Humphreys R.P. Thalamic tumors in children. Long-term follow-up and treatment guidelines. J. Neurosurg. 1984;61:649–656. doi: 10.3171/jns.1984.61.4.0649. PubMed DOI

Berzero G., Bellu L., Baldini C., Ducray F., Guyon D., Eoli M., Silvani A., Dehais C., Idbaih A., Younan N., Nguyen-Them L., Gaillard S., Pasqualetti F., Lepage-Seydoux C., Sekkate S., Tresca P., Kas A., Gratieux J., Ammari S., Saragoussi E., Savatovsky J., Delattre J.Y., Hoang-Xuan K., Meyronet D., Villa C., Bielle F., Sanson M., Touat M., Di Stefano A.L. Sustained tumor control with MAPK inhibition in BRAF V600-mutant adult glial and glioneuronal tumors. Neurology. 2021;97:e673–e683. doi: 10.1212/WNL.0000000000012330. PubMed DOI

Bilginer B., Narin F., Isikay I., Oguz K.K., Soylemezoglu F., Akalan N. Thalamic tumors in children. Childs Nerv Syst. 2014;30:1493–1498. doi: 10.1007/s00381-014-2420-9. PubMed DOI

Boesten T., Gerber N.U., Kandels D., Azizi A.A., Schmidt R., Warmuth-Metz M., Pietsch T., Kortmann R.D., Gnekow A., Grotzer M.A. Management of primary thalamic low-grade glioma in pediatric patients: results of the multicenter treatment studies HIT-LGG 1996 and SIOP-LGG 2004. Neurooncol Pract. 2017;4:29–39. doi: 10.1093/nop/npw007. PubMed DOI PMC

Bouffet E., Geoerger B., Moertel C., Whitlock J.A., Aerts I., Hargrave D., Osterloh L., Tan E., Choi J., Russo M., Fox E. Efficacy and safety of trametinib monotherapy or in combination with dabrafenib in pediatric BRAF V600-mutant low-grade glioma. J. Clin. Oncol. 2023;41:664–674. doi: 10.1200/JCO.22.01000. PubMed DOI PMC

Bouffet E., Hansford J.R., Garre M.L., Hara J., Plant-Fox A., Aerts I., Locatelli F., van der Lugt J., Papusha L., Sahm F., Tabori U., Cohen K.J., Packer R.J., Witt O., Sandalic L., Bento Pereira da Silva A., Russo M., Hargrave D.R. Dabrafenib plus trametinib in pediatric glioma with BRAF V600 mutations. N. Engl. J. Med. 2023;389:1108–1120. doi: 10.1056/NEJMoa2303815. PubMed DOI

Broadway S.J., Ogg R.J., Scoggins M.A., Sanford R., Patay Z., Boop F.A. Surgical management of tumors producing the thalamopeduncular syndrome of childhood. J. Neurosurg. Pediatr. 2011;7:589–595. doi: 10.3171/2011.4.PEDS119. PubMed DOI PMC

Carrabba G., Bertani G., Cogiamanian F., Ardolino G., Zarino B., Di Cristofori A., Locatelli M., Caroli M., Rampini P. Role of intraoperative neurophysiologic monitoring in the resection of thalamic astrocytomas. World Neurosurg. 2016;94:50–56. doi: 10.1016/j.wneu.2016.06.049. PubMed DOI

Celtikci E., Celtikci P., Fernandes-Cabral D.T., Ucar M., Fernandez-Miranda J.C., Borcek A.O. High-definition fiber tractography in evaluation and surgical planning of thalamopeduncular pilocytic astrocytomas in pediatric population: case series and review of literature. World Neurosurg. 2017;98:463–469. doi: 10.1016/j.wneu.2016.11.061. PubMed DOI

Cinalli G., Aguirre D.T., Mirone G., Ruggiero C., Cascone D., Quaglietta L., Aliberti F., Santi S.D., Buonocore M.C., Nastro A., Spennato P. Surgical treatment of thalamic tumors in children. J. Neurosurg. Pediatr. 2018;21:247–257. doi: 10.3171/2017.7.PEDS16463. PubMed DOI

Cuccia V., Monges J. Thalamic tumors in children. Childs Nerv Syst. 1997;13:514–520. doi: 10.1007/s003810050128. ; discussion 521. PubMed DOI

D'Amico A., Furlanis G.M., Baro V., Sartori L., Landi A., d'Avella D., Sala F., Denaro L. Thalamopeduncular tumors in pediatric age: advanced preoperative imaging to define safe surgical planning: a multicentric experience. J. Clin. Med. 2023;12 doi: 10.3390/jcm12175521. PubMed DOI PMC

Djirackor L., Halldorsson S., Niehusmann P., Leske H., Capper D., Kuschel L.P., Pahnke J., Due-Tonnessen B.J., Langmoen I.A., Sandberg C.J., Euskirchen P., Vik-Mo E.O. Intraoperative DNA methylation classification of brain tumors impacts neurosurgical strategy. Neurooncol Adv. 2021;3 doi: 10.1093/noajnl/vdab149. PubMed DOI PMC

Fisher P.G., Tihan T., Goldthwaite P.T., Wharam M.D., Carson B.S., Weingart J.D., Repka M.X., Cohen K.J., Burger P.C. Outcome analysis of childhood low-grade astrocytomas. Pediatr. Blood Cancer. 2008;51:245–250. doi: 10.1002/pbc.21563. PubMed DOI

Foley R., Boop F. Tractography guides the approach for resection of thalamopeduncular tumors. Acta Neurochir. 2017;159:1597–1601. doi: 10.1007/s00701-017-3257-2. PubMed DOI

Gajjar A., Sanford R.A., Heideman R., Jenkins J.J., Walter A., Li Y., Langston J.W., Muhlbauer M., Boyett J.M., Kun L.E. Low-grade astrocytoma: a decade of experience at st. Jude children's Research hospital. J. Clin. Oncol. 1997;15:2792–2799. doi: 10.1200/JCO.1997.15.8.2792. PubMed DOI

Gunny R.S., Hayward R.D., Phipps K.P., Harding B.N., Saunders D.E. Spontaneous regression of residual low-grade cerebellar pilocytic astrocytomas in children. Pediatr. Radiol. 2005;35:1086–1091. doi: 10.1007/s00247-005-1546-z. PubMed DOI

Gupta A., Shaller N., McFadden K.A. Pediatric thalamic gliomas: an updated review. Arch. Pathol. Lab Med. 2017;141:1316–1323. doi: 10.5858/arpa.2017-0249-RA. PubMed DOI

Haizel-Cobbina J., Thakkar R., Richard K., Du L., Levine A., Bennett J., Hawkins C., Tabori U., Dewan M.C. Clinical and molecular features of disseminated pediatric low-grade glioma and glioneuronal tumors: a systematic review and survival analysis. Neurooncol Adv. 2022;4 doi: 10.1093/noajnl/vdac122. PubMed DOI PMC

Haratek K., Bubenikova A., Entenmann C.J., Tomasek M., Zapotocky M., Sumerauer D., Kyncl M., Koblizek M., Liby P., Tichy M., Bradac O., Benes V., 3rd Predictors of postoperative complications and functional outcomes in pediatric patients with surgically treated fourth ventricle tumors. Acta Neurochir. 2023;165:4279–4292. doi: 10.1007/s00701-023-05729-w. PubMed DOI

Hoffman H.J., Soloniuk D.S., Humphreys R.P., Drake J.M., Becker L.E., De Lima B.O., Piatt J.H., Jr. Management and outcome of low-grade astrocytomas of the midline in children: a retrospective review. Neurosurgery. 1993;33:964–971. doi: 10.1227/00006123-199312000-00002. PubMed DOI

Kelly P.J. Stereotactic biopsy and resection of thalamic astrocytomas. Neurosurgery. 1989;25:185–194. ; discussion 194-5. PubMed

Krahulik D., Blazek F., Halaj M., Hrabalek L., Stepanova E., Pavelka Z., Rohanova M. Surgical treatment of paediatric thalamic gliomas-single-centre experience. Brain Sci. 2024;14 doi: 10.3390/brainsci14020141. PubMed DOI PMC

Krishnatry R., Zhukova N., Guerreiro Stucklin A.S., Pole J.D., Mistry M., Fried I., Ramaswamy V., Bartels U., Huang A., Laperriere N., Dirks P., Nathan P.C., Greenberg M., Malkin D., Hawkins C., Bandopadhayay P., Kieran M.W., Manley P.E., Bouffet E., Tabori U. Clinical and treatment factors determining long-term outcomes for adult survivors of childhood low-grade glioma: a population-based study. Cancer. 2016;122:1261–1269. doi: 10.1002/cncr.29907. PubMed DOI

Lee J., Mulder F., Leeflang M., Wolff R., Whiting P., Bossuyt P.M. QUAPAS: an adaptation of the QUADAS-2 tool to assess prognostic accuracy studies. Ann. Intern. Med. 2022;175:1010–1018. doi: 10.7326/M22-0276. PubMed DOI

Lee R.P., Foster K.A., Lillard J.C., Klimo P., Jr., Ellison D.W., Orr B., Boop F.A. Surgical and molecular considerations in the treatment of pediatric thalamopeduncular tumors. J. Neurosurg. Pediatr. 2017;20:247–255. doi: 10.3171/2017.4.PEDS16668. PubMed DOI PMC

Louis D.N., Perry A., Wesseling P., Brat D.J., Cree I.A., Figarella-Branger D., Hawkins C., Ng H.K., Pfister S.M., Reifenberger G., Soffietti R., von Deimling A., Ellison D.W. The 2021 WHO classification of tumors of the central nervous system: a summary. Neuro Oncol. 2021;23:1231–1251. doi: 10.1093/neuonc/noab106. PubMed DOI PMC

Menon G., Nair S., Sudhir J., Rao B.R., Krishnakumar K. Bilateral thalamic lesions. Br. J. Neurosurg. 2010;24:566–571. doi: 10.3109/02688691003777915. PubMed DOI

Page M.J., McKenzie J.E., Bossuyt P.M., Boutron I., Hoffmann T.C., Mulrow C.D., Shamseer L., Tetzlaff J.M., Akl E.A., Brennan S.E., Chou R., Glanville J., Grimshaw J.M., Hrobjartsson A., Lalu M.M., Li T., Loder E.W., Mayo-Wilson E., McDonald S., McGuinness L.A., Stewart L.A., Thomas J., Tricco A.C., Welch V.A., Whiting P., Moher D. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. Syst. Rev. 2021;10:89. doi: 10.1186/s13643-021-01626-4. PubMed DOI PMC

Puget S., Crimmins D.W., Garnett M.R., Grill J., Oliveira R., Boddaert N., Wray A., Lelouch-Tubiana A., Roujeau T., Di Rocco F., Zerah M., Sainte-Rose C. Thalamic tumors in children: a reappraisal. J. Neurosurg. 2007;106:354–362. doi: 10.3171/ped.2007.106.5.354. PubMed DOI

Qaddoumi I., Sultan I., Gajjar A. Outcome and prognostic features in pediatric gliomas: a review of 6212 cases from the Surveillance, Epidemiology, and End Results database. Cancer. 2009;115:5761–5770. doi: 10.1002/cncr.24663. PubMed DOI PMC

Reardon D.A., Gajjar A., Sanford R.A., Heideman R.L., Walter A.W., Thompson S.J., Merchant T.E., Li H., Jenkins J.J., Langston J., Boyett J.M., Kun L.E. Bithalamic involvement predicts poor outcome among children with thalamic glial tumors. Pediatr. Neurosurg. 1998;29:29–35. doi: 10.1159/000028681. PubMed DOI

Rosenberg T., Yeo K.K., Mauguen A., Alexandrescu S., Prabhu S.P., Tsai J.W., Malinowski S., Joshirao M., Parikh K., Farouk Sait S., Rosenblum M.K., Benhamida J.K., Michaiel G., Tran H.N., Dahiya S., Kachurak K., Friedman G.K., Krystal J.I., Huang M.A., Margol A.S., Wright K.D., Aguilera D., MacDonald T.J., Chi S.N., Karajannis M.A. Upfront molecular targeted therapy for the treatment of BRAF-mutant pediatric high-grade glioma. Neuro Oncol. 2022;24:1964–1975. doi: 10.1093/neuonc/noac096. PubMed DOI PMC

Rozen W.M., Joseph S., Lo P.A. Spontaneous regression of low-grade gliomas in pediatric patients without neurofibromatosis. Pediatr. Neurosurg. 2008;44:324–328. doi: 10.1159/000134925. PubMed DOI

Ryall S., Krishnatry R., Arnoldo A., Buczkowicz P., Mistry M., Siddaway R., Ling C., Pajovic S., Yu M., Rubin J.B., Hukin J., Steinbok P., Bartels U., Bouffet E., Tabori U., Hawkins C. Targeted detection of genetic alterations reveal the prognostic impact of H3K27M and MAPK pathway aberrations in paediatric thalamic glioma. Acta Neuropathol Commun. 2016;4:93. doi: 10.1186/s40478-016-0353-0. PubMed DOI PMC

Ryu H.H., Jung T.Y., Lee G.J., Lee K.H., Jung S.H., Jung S., Baek H.J. Differences in the clinical courses of pediatric and adult pilocytic astrocytomas with progression: a single-institution study. Childs Nerv Syst. 2015;31:2063–2069. doi: 10.1007/s00381-015-2887-z. PubMed DOI

Shah A.H., Madhavan K., Heros D., Raper D.M., Iorgulescu J.B., Lally B.E., Komotar R.J. The management of incidental low-grade gliomas using magnetic resonance imaging: systematic review and optimal treatment paradigm. Neurosurg. Focus. 2011;31:E12. doi: 10.3171/2011.9.FOCUS11219. PubMed DOI

Steinbok P., Gopalakrishnan C.V., Hengel A.R., Vitali A.M., Poskitt K., Hawkins C., Drake J., Lamberti-Pasculli M., Ajani O., Hader W., Mehta V., McNeely P.D., McDonald P.J., Ranger A., Vassilyadi M., Atkinson J., Ryall S., Eisenstat D.D., Hukin J. Pediatric thalamic tumors in the MRI era: a Canadian perspective. Childs Nerv Syst. 2016;32:269–280. doi: 10.1007/s00381-015-2968-z. PubMed DOI

Weiner H.L., Placantonakis D.G. Resection of a pediatric thalamic juvenile pilocytic astrocytoma with whole brain tractography. Cureus. 2017;9 doi: 10.7759/cureus.1768. PubMed DOI PMC

Wong T.T., Chen H.H., Liang M.L., Hsieh K.L., Yang Y.S., Ho D.M., Chang K.P., Lee Y.Y., Lin S.C., Hsu T.R., Chen Y.W., Yen S.H., Chang F.C., Guo W.Y., Chen K.W., Kwang W.K., Hou W.Y., Wang C.Y. Clinical considerations and surgical approaches for low-grade gliomas in deep hemispheric locations: thalamic lesions. Childs Nerv Syst. 2016;32:1895–1906. doi: 10.1007/s00381-016-3148-5. PubMed DOI

Xu C., Li C., Xing C., Li J., Jiang X. Efficacy of MR diffusion kurtosis imaging for differentiating low-grade from high-grade glioma before surgery: a systematic review and meta-analysis. Clin. Neurol. Neurosurg. 2022;220 doi: 10.1016/j.clineuro.2022.107373. PubMed DOI

Pediatric thalamic incidentalomas: a retrospective analysis of their characteristics, evolution, management, and prognostic factors for progression