Background: Diffuse gliomas are the most frequent neoplasms in adolescent and young adults (AYAs), especially high-grade gliomas, which have the highest mortality rate. Recent histo-molecular advances are in favour of specialized therapeutic management of AYA patients, which we have analysed in this comprehensive review of the literature. Summary: A literature search was conducted to identify all studies concerning diffuse gliomas and AYAs (15–39 years). We assessed epidemiology, clinical and imaging findings, histo-molecular characteristics, neurosurgical and neuro-oncological management, prognosis, and health-related quality of life. Key Messages: Diffuse gliomas remain the most frequent brain tumours in the AYA population. Symptoms mainly depend on the tumour location, which varies due to histo-molecular profiles. Specific imaging patterns of histo-molecular subtypes of diffuse gliomas are identified; however, no specific pattern related to the age group has been identified. The literature review favours optimizing the extent of surgical resection for diffuse gliomas, whichever the grade, and suggests a dedicated management for these patients. It seems more relevant to consider the treatment according to the histo-molecular profile of the diffuse glioma rather than the age group. Clinical trials will allow AYA patients to benefit from innovative therapies that could improve their outcome. This literature review suggests the need for a close and long-term psychological follow-up for AYA patients with brain tumour during the transitional care, during adulthood, as well as for their family members. Collaborative efforts are needed between paediatric and adult neurosurgical and neuro-oncological teams, to move forward in the therapeutic management of AYA patients harbouring diffuse gliomas.

Ng S, Zouaoui S, Bessaoud F, Rigau V, Roux A, Darlix A, et al. An epidemiology report for primary central nervous system tumors in adolescents and young adults: a nationwide population-based study in France, 2008–2013. Neuro Oncol. 2019 Jun;22(6):851–63.
Yamasaki F. Adolescent and young adult brain tumors: current topics and review. Int J Clin Oncol. 2022 Jan;27(3):457–64.
Closing the gap: research and care imperatives for adolescents and young adults with cancer. 2016; [cited 2022 May 31]. Available from:
Leibetseder A, Ackerl M, Flechl B, Wöhrer A, Widhalm G, Dieckmann K, et al. Outcome and molecular characteristics of adolescent and young adult patients with newly diagnosed primary glioblastoma: a study of the Society of Austrian Neurooncology (SANO). Neuro Oncol. 2013 Jan;15(1):112–21.
Kessler T, Sahm F, Sadik A, Stichel D, Hertenstein A, Reifenberger G, et al. Molecular differences in IDH wildtype glioblastoma according to MGMT promoter methylation. Neuro Oncol. 2018 Feb;20(3):367–79.
Paugh BS, Qu C, Jones C, Liu Z, Adamowicz-Brice M, Zhang J, et al. Integrated molecular genetic profiling of pediatric high-grade gliomas reveals key differences with the adult disease. J Clin Oncol. 2010 Jun;28(18):3061–8.
Mackay A, Burford A, Carvalho D, Izquierdo E, Fazal-Salom J, Taylor KR, et al. Integrated molecular meta-analysis of 1,000 pediatric high-grade and diffuse intrinsic pontine glioma. Cancer Cell. 2017 Oct 9;32(4):520–37.e5.
Roux A, Pallud J, Saffroy R, Edjlali-Goujon M, Debily M-A, Boddaert N, et al. High-grade gliomas in adolescents and young adults highlight histomolecular differences with their adult and paediatric counterparts. Neuro Oncol. 2020 Aug;22(8):1190–202.
Ostrom QT, Gittleman H, Xu J, Kromer C, Wolinsky Y, Kruchko C, et al. CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2009–2013. Neuro Oncol. 2016 Jan;18(Suppl 5):v1–75.
Tisnado J, Young R, Peck KK, Haque S. Conventional and advanced imaging of diffuse intrinsic pontine glioma. J Child Neurol. 2016 Oct;31(12):1386–93.
Pallud J, Capelle L, Taillandier L, Fontaine D, Mandonnet E, Guillevin R, et al. Prognostic significance of imaging contrast enhancement for WHO grade II gliomas. Neuro Oncol. 2009 Apr;11(2):176–82.
Roux A, Tauziede-Espariat A, Zanello M, Peeters S, Zah-Bi G, Parraga E, et al. Imaging growth as a predictor of grade of malignancy and aggressiveness of IDH-mutant and 1p/19q-codeleted oligodendrogliomas in adults. Neuro Oncol. 2020 Feb;22(7):993–1005.
Reyes-Botero G, Dehais C, Idbaih A, Martin-Duverneuil N, Lahutte M, Carpentier C, et al. Contrast enhancement in 1p/19q-codeleted anaplastic oligodendrogliomas is associated with 9p loss, genomic instability, and angiogenic gene expression. Neuro Oncol. 2014 May;16(5):662–70.
Pallud J, Mandonnet E, Duffau H, Kujas M, Guillevin R, Galanaud D, et al. Prognostic value of initial magnetic resonance imaging growth rates for World Health Organization grade II gliomas. Ann Neurol. 2006 Sep;60(3):380–3.
Roux A, Roca P, Edjlali M, Sato K, Zanello M, Dezamis E, et al. MRI atlas of IDH wild-type supratentorial glioblastoma: probabilistic maps of phenotype, management, and outcomes. Radiology. 2019 Oct;293(3):633–43.
Ellingson BM, Cloughesy TF, Pope WB, Zaw TM, Phillips H, Lalezari S, et al. Anatomic localization of O6-methylguanine DNA methyltransferase (MGMT) promoter methylated and unmethylated tumors: a radiographic study in 358 de novo human glioblastomas. NeuroImage. 2012 Jan;59(2):908–16.
Roux A, Tran S, Edjlali M, Saffroy R, Tauziede-Espariat A, Zanello M, et al. Prognostic relevance of adding MRI data to WHO 2016 and cIMPACT-NOW updates for diffuse astrocytic tumors in adults. Working toward the extended use of MRI data in integrated glioma diagnosis. Brain Pathol. 2021;31(4):e12929.
Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee WK, et al. The 2016 World health organization classification of tumors of the central nervous system: a summary. Acta Neuropathol. 2016 Jun;131(6):803–20.
Haque F, Varlet P, Puntonet J, Storer L, Bountali A, Rahman R, et al. Evaluation of a novel antibody to define histone 3.3 G34R mutant brain tumours. Acta Neuropathol Commun. 2017 06;5(1):45.
Roux A, Boddaert N, Grill J, Castel D, Zanello M, Zah-Bi G, et al. High prevalence of developmental venous anomaly in diffuse intrinsic pontine gliomas: a pediatric control study. Neurosurgery. 2020;86(4):517–23.
Hegi ME, Diserens A-C, Gorlia T, Hamou M-F, de Tribolet N, Weller M, et al. MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med. 2005 Mar;352(10):997–1003.
Appay R, Dehais C, Maurage C-A, Alentorn A, Carpentier C, Colin C, et al. CDKN2A homozygous deletion is a strong adverse prognosis factor in diffuse malignant IDH-mutant gliomas. Neuro Oncol. 2019 Dec;21(12):1519–28.
Louis DN, Perry A, Wesseling P, Brat DJ, Cree IA, Figarella-Branger D, et al. The 2021 WHO classification of tumors of the central nervous system: a summary. Neuro Oncol. 2021 Aug;23(8):1231–51.
Almuhaisen G, Alhalaseh Y, Mansour R, Abu-Shanab A, Al-Ghnimat S, Al-Hussaini M. Frequency of mismatch repair protein deficiency and PD-L1 in high-grade gliomas in adolescents and young adults (AYA). Brain Tumor Pathol. 2021 Jan;38(1):14–22.
Albright AL, Sposto R, Holmes E, Zeltzer PM, Finlay JL, Wisoff JH, et al. Correlation of neurosurgical subspecialization with outcomes in children with malignant brain tumors. Neurosurgery. 2000 Oct;47(4):879–85. discussion 885-7.
Khan UA, Bhavsar A, Asif H, Karabatsou K, Leggate JRS, Sofat A, et al. Treatment by specialist surgical neurooncologists improves survival times for patients with malignant glioma. J Neurosurg. 2015 Feb;122(2):297–302.
Profyris C, Chen E, Young IM, Chendeb K, Ahsan SA, Briggs RG, et al. Anaplastic oligodendroglioma: is adjuvant radiotherapy mandatory following maximal surgical resection?–grade 3 oligo radiotherapy. Clin Neurol Neurosurg. 2021 Jan;200:106303.
Guerreiro Stucklin AS, Tabori U, Grotzer MA. The changing landscape of pediatric low-grade gliomas: clinical challenges and emerging therapies. Neuropediatrics. 2016 Apr;47(2):70–83.
Persico P, Lorenzi E, Losurdo A, Dipasquale A, Di Muzio A, Navarria P, et al. Precision oncology in lower-grade gliomas: promises and pitfalls of therapeutic strategies targeting IDH-mutations. Cancers. 2022 Feb;14(5):1125.
Mellinghoff IK, Ellingson BM, Touat M, Maher E, De La Fuente MI, Holdhoff M, et al. Ivosidenib in isocitrate Dehydrogenase 1-mutated advanced glioma. J Clin Oncol. 2020 Oct;38(29):3398–406.
Mellinghoff IK, Penas-Prado M, Peters KB, Burris HA, Maher EA, Janku F, et al. Vorasidenib, a dual inhibitor of mutant IDH1/2, in recurrent or progressive glioma; results of a first-in-human phase I trial. Clin Cancer Res. 2021 Aug;27(16):4491–9.
Chassot A, Canale S, Varlet P, Puget S, Roujeau T, Negretti L, et al. Radiotherapy with concurrent and adjuvant temozolomide in children with newly diagnosed diffuse intrinsic pontine glioma. J Neurooncol. 2012 Jan;106(2):399–407.
Muroi A, Mizumoto M, Ishikawa E, Ihara S, Fukushima H, Tsurubuchi T, et al. Proton therapy for newly diagnosed pediatric diffuse intrinsic pontine glioma. Childs Nerv Syst. 2020 Mar;36(3):507–12.
Puthenpura V, Canavan ME, Poynter JN, Roth M, Pashankar FD, Jones BA, et al. Racial/ethnic, socioeconomic, and geographic survival disparities in adolescents and young adults with primary central nervous system tumors. Pediatr Blood Cancer. 2021 Jul;68(7):e28970.
Navarria P, Pessina F, Clerici E, Rossini Z, Franceschini D, D’Agostino G, et al. Is IDH status the only factor predicting prognosis in newly diagnosed anaplastic glioma patients? Outcome evaluation and prognostic factor analysis in a single-institution large series. J Neurosurg. 2020 Sep;135:64–77.
Bin-Alamer O, Jimenez AE, Azad TD, Bettegowda C, Mukherjee D. H3K27M-Altered diffuse midline gliomas among adult patients: a systematic review of clinical features and survival analysis. World Neurosurg. 2022 Sep;165:e251–64.
Jansen MHA, van Vuurden DG, Vandertop WP, Kaspers GJL. Diffuse intrinsic pontine gliomas: a systematic update on clinical trials and biology. Cancer Treat Rev. 2012 Feb;38(1):27–35.
Korshunov A, Schrimpf D, Ryzhova M, Sturm D, Chavez L, Hovestadt V, et al. H3-/IDH-wild type pediatric glioblastoma is comprised of molecularly and prognostically distinct subtypes with associated oncogenic drivers. Acta Neuropathol. 2017 Sep;134(3):507–16.
Varlet P, Le Teuff G, Le Deley M-C, Giangaspero F, Haberler C, Jacques TS, et al. WHO grade has no prognostic value in the pediatric high-grade glioma included in the HERBY trial. Neuro Oncol. 2020;22(1):116–27.
Tabouret E, Nguyen AT, Dehais C, Carpentier C, Ducray F, Idbaih A, et al. Prognostic impact of the 2016 WHO classification of diffuse gliomas in the French POLA cohort. Acta Neuropathol. 2016;132(4):625–34.
Sawicki GS, Lukens-Bull K, Yin X, Demars N, Huang IC, Livingood W, et al. Measuring the transition readiness of youth with special healthcare needs: validation of the TRAQ: Transition Readiness Assessment Questionnaire. J Pediatr Psychol. 2011 Mar;36(2):160–71.
Ferris ME, Harward DH, Bickford K, Layton JB, Ferris MT, Hogan SL, et al. A clinical tool to measure the components of health-care transition from pediatric care to adult care: the UNC TR(x)ANSITION scale. Ren Fail. 2012;34(6):744–53.
Cheung AT, Li WHC, Ho LLK, Ho KY, Chiu SY, Chan C-FG, et al. Impact of brain tumor and its treatment on the physical and psychological well-being, and quality of life amongst pediatric brain tumor survivors. Eur J Oncol Nurs. 2019 Aug;41:104–9.
Macartney G, Stacey D, Harrison MB, VanDenKerkhof E. Symptoms, coping, and quality of life in pediatric brain tumor survivors: a qualitative study. Oncol Nurs Forum. 2014 Jul;41(4):390–8.
Chow C, Liptak C, Chordas C, Manley P, Recklitis C. Adolescent and young adult brain tumor survivors report increased anxiety even years after successful treatment for relapse. J Adolesc Young Adult Oncol. 2019 Feb;8(1):90–3.
Corti C, Poggi G, Massimino M, Bardoni A, Borgatti R, Urgesi C. Visual perception and spatial transformation of the body in children and adolescents with brain tumor. Neuropsychologia. 2018 Nov;120:124–36.
Buchbinder DK, Fortier MA, Osann K, Wilford J, Shen V, Torno L, et al. Quality of life among parents of adolescent and young adult brain tumor survivors. J Pediatr Hematol Oncol. 2017 Nov;39(8):579–84.
Hays RD, Bjorner JB, Revicki DA, Spritzer KL, Cella D. Development of physical and mental health summary scores from the patient-reported outcomes measurement information system (PROMIS) global items. Qual Life Res. 2009 Sep;18(7):873–80.
National Institute for Health and Clinical Excellence. NICE guidance on cancer services: improving outcomes for people with brain and other CNS tumours: the manaual. London: National Institute for Health and Clinical Excellence; 2006.
Roux A, Beccaria K, Blauwblomme T, Mahlaoui N, Chretien F, Varlet P, et al. Toward a transitional care from childhood and adolescence to adulthood in surgical neurooncology? a lesson from the necker-enfants malades and the sainte-anne hospitals collaboration. J Neurosurg Pediatr. 2021 Jul;28(4):380–6.
Zapotocky M, Ramaswamy V, Lassaletta A, Bouffet E. Adolescents and young adults with brain tumors in the context of molecular advances in neuro-oncology. Pediatr Blood Cancer. 2018 Feb;65(2):e26861.
You do not currently have access to this content.