====== Diffuse intrinsic pontine glioma outcome ======

When [[DIPG]]s are biopsied, they are usually grade III or grade IV. Occasionally, they are grade II, but because of their location in the brain they are still considered malignant. That being said, [[diffuse intrinsic pontine glioma]]s usually progress like grade IV [[glioblastoma multiforme]] tumors. 

[[Diffuse Intrinsic Pontine Glioma]] is the most aggressive form of [[high-grade glioma ]]s in [[child]]ren it is incurable, aggressive, and disabling due to localization in the midline [[brainstem]]. 

They are universally fatal and associated with progression free and median overall survival rates of 5.7 and 7.9 mo, respectively
((Veldhuijzen van zanten SE, Van meerwijk CL,
Jansen MH, et al. Palliative and end-of-life care
for children with diffuse intrinsic pontine glioma:
results from a London cohort study and international
survey. Neuro Oncol. 2016;18(4):582-588.)).

Despite advances in neurosurgery, radiotherapy, and chemotherapy trials, current treatment
strategies only serve as palliation. New therapies that are specific to DMG are under active investigation.
An exciting and novel approach developed by Mount et al
((Mount CW, Majzner RG, Sundaresh S, et al.
Potent antitumor efficacy of anti-[[GD2]] CAR T cells
in H3-K27M+ diffuse midline gliomas. Nat Med.
2018;24(5):572-579.)),
may significantly advance care for these lethal tumors by using anti-GD2 chimeric antigen receptor (CAR)-modified T cells to target [[GD2]], an antigen that is highly expressed on tumors of neuroectodermal origin such as neuroblastoma and melanoma.

CAR T cells were originally developed by Kochenderfer et al
((Kochenderfer JN, Wilson WH, Janik JE, et al.
Eradication of B-lineage cells and regression of
lymphoma in a patient treated with autologous
T cells genetically engineered to recognize CD19.
Blood. 2010;116(20):4099-4102.))
against leukemia and lymphoma but have recently been adapted and explored as immunotherapy against central nervous system tumors. CAR T
cells are synthetically engineered from a patient’s autologous T-cells to recognize
cancer-specific antigens and generate a strong anti-tumor immune response.

Diffuse midline glioma, H3 [[K27M]]-mutant, represents a newly introduced, predominantly astrocytic tumor of pons, thalamus, or spinal cord with poor prognosis and a K27M mutation in one of three histone genes. While the H3 K27M mutation had been considered as being the defining mutation of this brain tumor group, it may also occur in other brain tumors, such as pilocytic astrocytoma 
((Orillac C, Thomas C, Dastagirzada Y, Hidalgo ET, Golfinos JG, Zagzag D, Wisoff
JH, Karajannis MA, Snuderl M. Pilocytic astrocytoma and glioneuronal tumor with
histone H3 K27M mutation. Acta Neuropathol Commun. 2016 Aug 12;4(1):84. doi:
10.1186/s40478-016-0361-0. PubMed PMID: 27519587; PubMed Central PMCID:
PMC4983033.
))
and ependymoma 
((Gessi M, Capper D, Sahm F, Huang K, von Deimling A, Tippelt S, Fleischhack G, 
Scherbaum D, Alfer J, Juhnke BO, von Hoff K, Rutkowski S, Warmuth-Metz M, Chavez 
L, Pfister SM, Pietsch T, Jones DT, Sturm D. Evidence of H3 K27M mutations in
posterior fossa ependymomas. Acta Neuropathol. 2016 Oct;132(4):635-7. doi:
10.1007/s00401-016-1608-3. PubMed PMID: 27539613.
))
, without necessarily being associated with poor prognosis. Whether these tumors have to be classified as diffuse midline glioma (grade IV) with aberrant phenotype or as low-grade glioma with unusual H3 K27M mutation remains unclear to date. These cases certainly represent only a small minority of brain tumors, but their classification poses problems.
----
[[T2-FLAIR mismatch sign]] in DIPG may be an indicator for better response to radiotherapy and a better prognostic factor
((Yamasaki F, Nishibuchi I, Karakawa S, Kaichi Y, Kolakshyapati M, Takano M, Yonezawa U, Imano N, Taguchi A, Shimomura M, Taniguchi M, Onishi S, Okada S, Awai K, Sugiyama K, Nagata Y. T2-FLAIR Mismatch Sign and Response to Radiotherapy in Diffuse Intrinsic Pontine Glioma. Pediatr Neurosurg. 2021 Feb 3:1-9. doi: 10.1159/000513360. Epub ahead of print. PMID: 33535215.)).

===== References =====