tbuckley/cabot-search huggingface dataset:
DIPG-37. AUGMENTING RADIATION SENSITIVITY IN DMG/DIPG BY TARGETING TP53 DEPENDENCY AND INHIBITING DNA PROTEIN KINASE PATHWAY
Authors: Ludovica Ciani, Solène Fernandez, Micheal Grotzer, Sabine Müller, Javad Nazarian
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Diffuse midlines gliomas (DMGs) are lethal pediatric brain tumors, with an overall survival rate of less than 12 months. Radiotherapy treatment (RT) only provides a transient clinical response, with an average survival increase of about 3 months. At the cell level it induces DNA damages, leading to tumor cell death. Although, DMGs are tumors known to be resistant to any therapy, as the tumor recurs most often within a few months post radiation. Peposertib, a DNA Protein Kinase (DNA-PK) inhibitor, is a potent radiosentitizer that crosses the blood brain barrier and has shown RT-combination efficacy in other cancers by enhancing DNA double-strand breaks (DSB) inducing agents including ionising radiation. Methods and RESULTS DNA-PK plays a key role in one of the main pathways involved in the repair of DNA double-strand breaks (DSB), allowing tumor cells to repair their DNA and continue proliferation. To further investigate Peposertib and its potential for clinical intervention, we explored Peposertib’s radiosensitizing activity on DMG preclinical in vitro models. In vitro viability assays with RT alone and in combination with Peposertib, were carried out using DMG cell lines carrying either the wild-type or mutated version of TP53. To further validate our results, immunofluorescence assays post-combination treatment were performed to assess DDR pathway disruption by studying the number of foci per nucleus of DNA damage markers yH2AX and P53BP1. RESULTS Remarkably, combinational treatment of Peposertib with RT resulted in a significant decrease in human primary DMG cells viability. Interestingly, Peposertib was effective in increasing RT sensitivity in TP53WT DMGs. However, the same good response was not observed in the DMG cell lines carrying TP53MUT, indicating a possible correlation between TP53 mutational status and response to therapy. Additionally, we demonstrated that Peposertib induces cell death. This was observed and determined through quantification analysis of DNA damage markers yH2AX and P53BP1 therefore to DDR pathway disruption. CONCLUSIONS Our current findings underscore Peposertib’s potential as a targeted therapeutic agent against DMGs, offering a better understanding of what drives resistance to radiotherapy. By targeting DDR pathway key factors we will increase sensitivity to radiation in vitro and in vivo in DMGs.
HGG-13. INFANT-TYPE HEMISPHERIC GLIOMA (IHG): AN INDIVIDUAL PATIENT DATA META-ANALYSIS
Authors: Lara Chavaz, Aditi Bagchi, Fabienne Toutain, Stefan M Pfister, Dominik Sturm, Torsten Pietsch, Gerrit H Gielen, Andreas Waha, Matthew Clarke, Michael Karremann, Martin Benesch, Thomas Perwein, Gunther Nussbaumer, Christof Kramm, Maura Massimino, Veronica Biassoni, Maria Vinci, Angela Mastronuzzi, Dannis van Vuurden, Sophie E M Veldhuijzen van Zanten, Alan Mackay, Chris Jones, David T W Jones, Ana S Guerreiro Stucklin, Uri Tabori, Cynthia Hawkins, Scott Ryall, Andrés Morales La Madrid, Alvaro Lassaletta, Simon Bailey, Darren Hargrave, Jason Chiang, Moatasem El-Ayadi, Bruna Minniti Mançano, Rui Manuel Reis, Christian Hagel, Giles W Robinson, Amar Gajjar, Hamza Gorsi, Nicolas Silvestrini, Andre O von Bueren
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Infant-type hemispheric gliomas (IHG) are epigenetically distinct pediatric high-grade gliomas characterized by fusions in receptor tyrosine kinase (RTK) genes. METHODS We performed a methodical literature search, including 30 publications (22 case reports), to identify patients who met the diagnostic criteria of IHG based on the 2021 WHO Classification of CNS Tumors. Individual patient data were obtained from published literature and/or via the authors of the publications. Survival analysis was conducted using the Kaplan-Meier method, and multivariate analysis was performed to investigate the effect of clinical and molecular variables on outcomes. RESULTS Hundred-fifty-five previously reported and one unpublished IHG were identified: 131 (84%) had fusions in RTK genes, of which ALK was most prevalent (62/131), followed by NTRK1/2/3 (30/131), ROS1 (30/131), and MET (9/131). Twenty-five patients, with either no identified RTK fusion (6/156) or not assessable fusion (19/156), had methylation scores ≥ 0.9 for IHG (using the Molecular Neuropathology brain tumor classifier versions ≥ 11b4). Surgery followed by adjuvant chemotherapy in 69% (67/97) was the most common primary treatment used in our cohort. The 3-year EFS and OS were 55% (95%CI: 45-67) and 81 % (95%CI: 73-89). 41 patients with relapsed or progressive tumors received various second-line treatments including surgery, chemotherapy, radiotherapy, and targeted therapy. Based on multivariate analysis, complete resection resulted in better EFS (p = 0.05) and OS (p = 0.009), and the presence and type of RTK gene fusion were not associated with clinical outcomes. CONCLUSION Our results show that despite favorable OS, patients with IHG often show early progression, indicating that the primary optimal treatment for IHG is yet to be established. Our analysis further indicates that achieving a safe, complete resection may play an important role in treating these patients. A comprehensive analysis of the salvage regimen is required to understand their role in OS.
IMG-25. PREDICTING ANATOMICAL TUMOR GROWTH IN PEDIATRIC HIGH-GRADE GLIOMAS VIA DENOISING DIFFUSION MODELS
Authors: Daria Laslo, Maria Monzon, Divya Ramakrishnan, Marc von Reppert, Schuyler Stoller, Ana Sofia Guerreiro Stücklin, Nicolas U Gerber, Andreas Rauschecker, Javad Nazarian, Sabine Mueller, Catherine R Jutzeler, Sarah C Brüningk
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Pediatric diffuse midline glioma (DMG) has a poor prognosis with radiotherapy as the standard of palliative care. Radiation strategies using individual geometric doseshaping have the potential to maximize patient benefit. This study aimed to establish a proof-of-principle to generate clinically relevant anatomical representations of the progression of pediatric DMG magnetic resonance image (MRI) slices through denoising diffusion implicit models (DDIM). METHODS Based on the BraTS23 data, we analyzed the generation of MRIs with enlarged tumor sizes starting from a baseline scan. Models were pre-trained on adult glioblastoma (GBM) prior to transfer learning on pediatric high-grade glioma. Test set performance was evaluated using the Frechet Inception Distance (FID), and Structural Similarity Index (SSIM). Qualitative evaluation involved visual classification of real vs generated images by two independent radiology trainees. The optimized network was tested to forecast anatomical tumor growth in five DMG patients from an independent dataset comprising longitudinal T2-FLAIR images. RESULTS We obtain high-fidelity generated images, supported by an FID of 12.4 and 0.8 SSIM on the adult test set. Despite the smaller pediatric BraTS dataset yielding a 34.8 FID and 0.84 SSIM, human observers failed to distinguish generated from real MRIs (mean recall and precision of 0.51). The generated anatomical predictions also closely resemble the observed longitudinal tumor progression in the pediatric DMG subset. Notably, the direction and extent of tumor growth align while the surrounding brain anatomy is preserved. Quantitatively, the mean DICE score between segmentations of generated and real tumors was 0.8. CONCLUSIONS Our model produces high-quality images that conform to growth patterns of pediatric DMGs. Further quantitative validation on larger longitudinal datasets is required, to ensure the method’s robustness. The proposed method enables a personalized approach for defining target regions in radiation therapy which could translate to improved clinical outcomes.
HGG-06. MOLECULAR PATTERNS OF PEDIATRIC HIGH-GRADE GLIOMAS IN SOUTHEAST ASIA
Authors: Sze Jet Aw, Khurshid Merchant, Jian Yuan Goh, Yingting Mok, Char Loo Tan, Enrica Ee Kar Tan, Sharon Yin Yee Low, Kenneth Tou En Chang
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Molecular characteristics of pediatric high-grade gliomas are largely based on cohorts derived from North America and Europe. In this study, we compare the molecular findings of a Southeast Asian cohort of pediatric high-grade gliomas with published data. METHODS We collated clinical, histopathological, and molecular data from pediatric high-grade gliomas diagnosed in our laboratory over the past 5 years. Molecular testing methods used included Illumina’s Childhood Cancer Panel (26 cases), FoundationOne’s CDx panel (2 cases), and Archer FUSIONPlex Pan Solid Tumour v2 panel (2 cases). 7 cases had no molecular data. 11 cases underwent additional DNA methylation analysis using Illumina’s Infinium MethylationEPIC v1.0 kit. RESULTS 37 cases of pediatric high-grade gliomas from 34 patients were identified. Patient age ranged from 2 to 26 years (median 14 years). The male-female ratio was 1.1:1. Diffuse midline gliomas, H3K27-altered (DMG, H3K27-altered) constituted 51% of the cases (19/37), followed by diffuse pediatric-type high-grade gliomas, H3-wildtype and IDH-wildtype (32%; 12/37) and diffuse hemispheric gliomas H3G34-mutant (16%; 6/37). The commonest genes with pathogenic single nucleotide variants were TP53 (79%;22/28), followed by H3F3A (54%;15/28). The commonest amplified genes were MYCN and EGFR (both 4/28; 14%). Three gene fusions were detected, none of which arose from infants – 2 were found in diffuse pediatric-type high-grade gliomas, H3-wildtype and IDH-wildtype (CSTF3::ALK and PRCC::NTRK1 fusions), and one occurred in a DMG, H3K27-altered (ERC1::RET fusion). The most common methylation groups identified were DMG, H3K27-altered and diffuse pediatric-type high-grade glioma, H3-wildtype and IDH-wildtype, MYCN subtype (both 3/11; 27%). CONCLUSIONS Although small, our Southeast Asian cohort comprised a higher percentage of TP53-mutant high-grade gliomas amongst all pediatric high-grade gliomas as a group. The commonest amplified genes were MYCN and EGFR. We detected gene fusions in non-infant gliomas. These findings suggest geographical differences in the biology of pediatric high-grade gliomas.
EPEN-11. CHARACTERIZING EPIGENETIC MODULATIONS AND EZHIP DOWNSTREAM TARGETS IN PFA EPENDYMOMA
Authors: Shanzheng Wang, Anne Jenseit, Jens-Martin Hübner, Monika Mauermann, Konstantin Okonechnikov, Stefan M Pfister, Marcel Kool
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Ependymomas can arise from all compartments of the central nervous system and ten distinct molecular groups have been identified in children and adults. In children, the most aggressive group is posterior fossa group A ependymoma (PFA). In PFA ependymomas, the aberrant overexpression of EZHIP (EZH inhibitory protein) has been implicated as a relevant driver of the disease. EZHIP suppresses the installing and spreading of the repressive epigenetic mark H3K27me3 via disturbing PRC2 (polycomb repressive complex 2) activity through inhibiting EZH2 (enhancer of zeste 2), which causes overall low levels of H3K27me3 in PFA. METHODS To get a better understanding how EZHIP may drive the disease, how it affects the epigenetic landscape and what the downstream targets of EZHIP are, we performed DNA sequencing, RNA expression profiling and ChIP-seq experiments of H3K27me3, H3K27ac, EZH2, and EZHIP in PFA, PFB, and ST-ZFTA ependymomas (n = 3 tumor cases each). RESULTS After validating the high levels of EZHIP and global reduction of H3K27me3 in PFA, we characterized the epigenetic landscape and EZHIP chromatin binding characteristics in PFA compared to PFB and ST-ZFTA ependymoma. Transcriptome analysis showed that overall more genes are up-regulated in PFA compared with PFB and ZFTA, which might be caused by its relatively high accessibility with a global loss of H3K27me3. EZHIP knockdown experiments confirmed direct changes on H3K27me3, H3K27ac and gene expression. We also found that PLAG1 (pleomorphic adenoma gene 1) expression linearly correlated with EZHIP expression in PFA tumors. ChIP-seq data indeed showed the PLAG1 locus to be bound by EZHIP and marked with increased H3K27ac and decreased H3K27me3 signals in PFA. CONCLUSIONS We identified PLAG1 as a potential downstream target of EZHIP in PFA tumors. Currently, more experiments on PLAG1 are being performed to further explore its role as a potential vulnerability in PFA ependymoma.
CP-13. MRI-DERIVED NUCHAL SKINFOLD THICKNESS AS AN INDEX OF BODY COMPOSITION IN CHILDHOOD-ONSET CRANIOPHARYNGIOMA
Authors: Eshaa Vijay, Julia Crowley, Michael J Fisher, Cassie Kline, Karuna Shekdar, Shana E McCormack
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Survivors of childhood craniopharyngioma often develop obesity. Body mass index (BMI) is an imperfect estimate of adiposity. Nuchal skinfold thickness (NST) is a measure of upper body adiposity obtainable from routine surveillance brain MRIs. Our objective was to evaluate whether NST adds more information than BMI alone regarding excess adiposity in survivors of childhood craniopharyngioma. METHODS This was a single-site, retrospective review of children (all ages) diagnosed with craniopharyngioma between 2008 and 2020 with data at baseline, and 6 (±2) and 12 (±2) months follow-up (2008-2020). NST was measured on a mid-sagittal T1-weighted MRI image, on the line crossing the anterior and posterior margins of the foramen magnum. BMI Z-scores (BMI-Z) were calculated using extended CDC references. Mixed effects regression assessed change in NST related to time from diagnosis and BMI-Z, accounting for age and sex. RESULTS Thirty-two patients met criteria (female, n=9 [28%]; median age 8.3y [range, 2.1-15.5] at diagnosis). Mean BMI Z-scores were 0.82 (SD 1.38) at diagnosis, 1.44 (1.07) at 6 months (p=0.004 vs. diagnosis), and 1.40 at 12 months (p=0.01 vs. diagnosis). Median nuchal thickness was 7.1 mm (IQR 5.8, 9.5) at diagnosis, 9.7 mm (IQR 7.8, 10.7) at 6 months (p=0.001 vs. diagnosis), and 10.1 mm (IQR 8.1, 12.6) at 12 months (p=0.0001 vs. diagnosis). As expected, nuchal thickness positively associated with BMI-Z (β, 1.3, p&amp;lt;0.001). Even after accounting for age, sex, and change in BMI-Z, NST was higher at 12 months as compared to diagnosis (β, 1.8, p=0.004). CONCLUSION BMI-Z and NST increase over time in children with craniopharyngioma. Increases in NST are not explained by increases in BMI-Z alone, suggesting that NST reflects an additional dimension of body composition. Next, we will evaluate how including NST along with BMI improves cardiometabolic risk prediction in childhood craniopharyngioma. FUNDING Finamore Family Research Fund.
STEM-06. THE ROLE OF SHH SIGNALING PATHWAY IN RETINOBLASTOMA INITIATION AND PROGRESSION
Authors: Xiao Liu, Najiba Murad, Yanxin Pei, McKayla Bridgette Micklye
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Retinoblastoma is a rare childhood cancer of the retina that shows the biallelic loss of RB1 in nearly 95% of cases. It was reported that SHH pathway proteins, such as SHH, GLI1, and GLI2, are aberrantly high in human retinoblastoma, and high GLI2 expression is associated with aggressive clinicopathological features. Thus, we assessed whether activation of SHH pathway by overexpression of Gli2 or SMO induces the initiation of retinoblastoma. METHODS We generated a Cre-activated, Doxycycline (Dox)-controlled transgenic model to induce SMO or Gli2 expression in developing retina. In this transgenic mouse, expression of Smo or Gli2A is under the control of TRE, which permits temporal and spatial expression of Smo or Gli2A by administering/withdrawing doxycycline (DOX). RESULTS We fed the triple transgenic mice (Chx10-Cre/R26-LSL-rtTA/tetO-Smo or Chx10-Cre/R26-LSL-rtTA/tetO-Gli2A starting from E0 or P5. Our studies demonstrated that control littermates (Cre-) did not show any abnormalities, while mice with triple transgenes developed tumors in the bilateral eyes with 100% morbidity. The animals showed symptoms of leukocoria at P0-P3 or P25-p30 if the oncogenes were initiated at E0 or P5 respectively. The tumor cells were highly proliferative and expressed retina progenitor cell specific marker of Sox2, showing aberrant expression of pRB, CDK4/6, and CCND1. CONCLUSIONS Our results demonstrate that overexpressing Smo or Gli2 in Chx10+ cells induce rapid tumor formation in mouse retina. In future study, we plan to (i) investigate the impact of Shh pathway activation in RPCs on RB tumorigenesis within the context of Rb1 loss; (ii) define the molecular mechanisms underlying tumor initiation and progression; and (iii) evaluate whether targeting SHH pathway prevents or delays tumor initiation and progression using our Gli2-driven mouse model and patient-derived xenografts.
HGG-08. DIFFUSE HEMISPHERIC GLIOMA, H3 G34-MUTANT: A MULTI-INSTITUTIONAL EXPERIENCE
Authors: Dana Tlais, Jordan T Roach, Christopher L Tinkle, Qunyu Zhang, Xiaoyu Li, Tong Lin, Rene Y McNall-Knapp, Sarah Z Rush, Brian H Le, Sara Sinno, Apeksha Agarwal, Kevin F Ginn, Richard M Green, Arzu Onar-Thomas, Asim K Bag, Jason Chiang
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Diffuse hemispheric glioma (DHG), H3 G34-mutant, is a rare, aggressive brain tumor molecularly defined by mutations in the H3-3A gene. Our study explored the association between patient outcomes and key molecular findings, resection extent, and temozolomide (TMZ) use. METHODS Multi-institutional chart and molecular analysis of 32 patients with H3 G34-mutant DHG. RESULTS The median patient age was 14 (10-28 years), with a M/F ratio of 1.4. The 1-year, 2-year, and 5-year PFS were 40.4% (23.7%, 57.1%), 22.1% (9.0%, 38.7%), and 11.0% (1.9%, 33.7%), respectively. The 1-year, 2-year, and 5-year OS were 82.5% (63.2%, 92.3%), 49.3% (28.7%, 66.3%), and 29.6% (9.1%, 50.6%), respectively. Patients who underwent a gross total resection (GTR) had improved PFS (p=0.0105) and OS (p=0.0184) compared to non-GTR patients. 22 patients (68.8%) received concurrent and/or adjuvant TMZ and had improved PFS (p=0.0278) compared to patients who did not receive front-line TMZ. Disease recurrence in relation to the radiation therapy (RT) field was analyzed in 17 patients; 5 recurred locally within the high-dose RT field, 5 recurred distantly, and 7 had both local and distant recurrences. There was no significant association between MGMT promoter methylation status (18 evaluable cases), PDGFRA amplification (N=6), and CDKN2A homozygous deletion (N=10) and survival outcomes. MGMT promoter methylation was not associated with increased TMZ efficacy (N=8 with MGMT silencing, N=4 without). CONCLUSIONS In our cohort, MGMT promoter methylation was not a favorable prognostic factor, in distinction from prior reports in adult and pediatric high-grade gliomas. Resection extent and the use of TMZ were associated with improved survival outcomes. As most treatment failures occurred within the high-dose RT field, extended fields do not appear warranted. Our findings may guide prognostic and therapeutic decisions in patients with H3 G34-mutant DHG and support the need for prospective efforts to improve outcomes in this patient population.
EPEN-01. DISTINCT RELAPSE PATTERN ACROSS MOLECULAR EPENDYMOMA TYPES
Authors: Denise Obrecht-Sturm, Melanie Schoof, Alicia Eckhardt, Martin Mynarek, Mark R Gilbert, Kenneth Adalpe, Terri S Armstrong, Vijay Ramaswamy, Michael L Bockmayr, Katja von Hoff, Gudrun Fleischhack, Jonas E Adolph, Stephan Tippelt, Stefan M Pfister, Kristian Pajtler, Dominik Sturm, Richard Drexler, Franz L Ricklefs, Natalia Stephien, Johannes Gojo, Torsten Pietsch, Monika Warmuth-Metz, Rolf-Dieter Kortmann, Beate Timmermann, Christine Haberler, Stefan Rutkowski, Ulrich Schüller
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Ependymoma (EPN) is not a uniform disease but represents different tumor types with biological and clinical heterogeneity. Some types have an excellent prognosis; others display frequent relapse. However, the pattern of when and where different types of EPN relapse is largely unknown. METHODS We assembled 552 intracranial EPN from pediatric (n=445) and adult (n=107) patients from European and Northern American cohorts and correlated DNA methylation patterns and copy-number alterations with clinical information. Median age at diagnosis was 13.4±18.8 (0.1 – 80) years. RESULTS In 271/552 (49.1%) of included EPN relapse occurred. First relapses occurred in the initial tumor bed in 70.9%, 22.4% were metastatic only, and 6.7% were combined local and metastatic. First relapses of PF-EPN-B (PF: posterior-fossa) and PF-EPN-SE (SE: subependymoma) occurred later than of PF-EPN-A, ST-EPN-YAP (ST: supratentorial), or ST-EPN-ZFTA (median time to relapse: 4.3 and 6.0 years vs. 1.9/1.0/2.5 years; p&amp;lt;0.01). Metastatic or combined recurrences in PF-EPN-B and -A occurred more often in the spinal cord than in ST-EPN-ZFTA (75.0% and 40.0% vs. 12.5%; p&amp;lt;0.01). In the latter, relapse occurred more frequently when harboring an alternative fusion or CDNK2A loss (p&amp;lt;0.01, respectively). No distant relapses were observed in ST-EPN-YAP (n=9) or PF-EPN-SE (n=60). Post-relapse survival (PRS) was poor for PF-EPN-A and ST-EPN-ZFTA (5-year PRS: 44.5±4.4/ 47.8±9.1%), whereas PF-EPN-B and PF-EPN-SE displayed a 5-year PRS of 89.5±7.1/ 90.0±9.5% (p=0.03). However, 10-year PRS for PF-EPN-B dropped to 45.8±17.3%. CONCLUSIONS Relapse patterns of specific EPN types are different. Duration of surveillance and diagnostics should be planned incorporating entity-specific relapse information. Follow-up should be performed longer than 5 years after diagnosis. Spinal MRI should be considered as standard procedure during surveillance, particularly for PF-EPN-A, PF-EPN-B and ST-EPN-ZFTA.
DIPG-40. LONG TERM SURVIVAL OF A 14 YEAR OLD GIRL WITH H3K27M MUTATED DIFFUSE MIDLINE GLIOMA FOLLOWING RADIOTHERAPY AND PROLONGED TUMOR TREATING FIELDS (TTFIELDS) -CASE REPORT
Authors: Rina Dvir
Journal: Neuro-Oncology (2024)

Abstract INTRODUCTION Pediatric diffuse midline H3K27M mutated glioma has a dismal prognosis. Most cases are treated by radiotherapy and oral chemotherapy, with surgical resection having a debatable role in some. Tumor-treating fields (TTFields) is a noninvasive modality in which alternating electrical fields exert biophysical force on charged and polarizable molecules known as dipoles. TTFields has been shown to extend survival for adult patients with newly diagnosed and recurrent GBM, and is FDA approved for these indications. There is sparse data about pediatric patients. CASE REPORT A 14-year-old girl presented with headache and vomiting. A large left thalamic tumor was diagnosed and underwent subtotal resection. Diagnosis was diffuse midline glioma, H3K27M positive, IDH negative. Molecular Panel: Tumor mutation burden low, microsatellite stable. Genomic findings: FGFR1, NF1, H3F3A -K28M, ATRX R666, MAP3K1 She was re-operated due to a fast tumor relapse within a few weeks, prior to radiotherapy, followed with radiotherapy with local field 59Gy. She then received temozolamide (12 months) concomitant with TTfields (Optune, Novocure). TTfields therapy was administered for 5 years without adverse effects and excellent compliance (above 85%). After 5 years, therapy was withheld, and she is now off therapy NED for another 15 months. DISCUSSION Diffuse midline H3K27M glioma harbors a poor prognosis in children. Children refrain from this treatment both for lack of evidence and because of the difficulty in adhering to a regimen that demands carrying a battery of 1.5-2kg all day and shaving all hair every 3 days. Our patient had a high compliance and as she wore a head scarf for religious customs, the device was not visible. To our knowledge this is the first pediatric reported case of long-term survival of H3K27mutatted midline glioma using TTFields. Further pediatric studies are warranted.