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Challenges and New Strategies in the Management of Pediatric Brain...
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Challenges and New Strategies in the Management of Pediatric Brain Tumors

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Pediatric Oncology".

Deadline for manuscript submissions: closed (30 June 2024) | Viewed by 12938

Special Issue Editors

Dr. Semi B. Harrabi

E-Mail Website
Guest Editor
Heidelberg Ion Beam Therapy Center (HIT), Department of Radiation Oncology, University Hospital of Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany
Interests: pediatric oncology; pediatric brain tumors; neuro-oncology; proton beam therapy; ion beam therapy; high-precision radiotherapy
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Adilia Hormigo

E-Mail Website
Guest Editor
Department of Oncology, Albert Einstein College of Medicine, Montefiore Einstein Cancer Center, Bronx, NY 10461, USA
Interests: neuro-oncology; primary brain tumors; cancer immunology

Special Issue Information

Dear Colleagues,

Pediatric brain tumors present a unique set of challenges in terms of diagnosis, treatment and long-term outcome. The broad range of different tumor types is complex and heterogenous with regard to genetic mutations and biological behavior, making it difficult to identify optimal treatment strategies that are both safe and effective across all subtypes. Advances in personalized medicine, such as targeted therapy, immunotherapy or high-precision ion beam therapy, have increased the therapeutic window in these patients. This Special Issue aims to highlight the recent advances in the interdisciplinary management of pediatric brain tumor patients to further improve the outcomes of pediatric brain tumor patients, whilst minimizing the risk for long-term side effects.

We welcome Reviews and Original Articles on any aspect related to this topic.

Dr. Semi B. Harrabi
Prof. Dr. Adilia Hormigo
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • low-grade glioma
  • high-grade glioma
  • ependymoma
  • medulloblastoma
  • craniopharyngioma
  • germinoma
  • molecular pathways
  • radiotherapy
  • targeted therapy
  • immunotherapy
  • neuroradiology
  • neurosurgery
  • new treatment strategies
  • long-term outcome

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Published Papers (5 papers)

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Research

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12 pages, 813 KiB  
Article
Intensive Interdisciplinary Rehabilitation in the Pediatric Hematology/Oncology Setting: Feasibility and Perceived Benefit of the Acute Neurological Injury Service
by Darcy Raches, Amar Gajjar, Giles W. Robinson, Jason M. Ashford, Martina Bryndziar, April Huggins, Sherry Lockett, Allison Harris, Hannah Taylor, Ellen Bursi and Heather M. Conklin
Cancers 2024, 16(17), 2999; https://doi.org/10.3390/cancers16172999 - 29 Aug 2024
Viewed by 1141
Abstract
(1) Background: Intensive interdisciplinary rehabilitation services more effectively promote recovery from acquired brain injury than a single discipline approach. However, research literature is lacking regarding the perceived feasibility and utility of an interdisciplinary approach across disciplines for patients within a tertiary care pediatric [...] Read more.
(1) Background: Intensive interdisciplinary rehabilitation services more effectively promote recovery from acquired brain injury than a single discipline approach. However, research literature is lacking regarding the perceived feasibility and utility of an interdisciplinary approach across disciplines for patients within a tertiary care pediatric hematology/oncology setting. (2) Methods: The Acute Neurological Injury (ANI) service applied an acquired brain injury/inpatient rehabilitation interdisciplinary approach to a pediatric hematology/oncology population, with a focus on interdisciplinary communication, shared goal setting, and coordinated transition planning. Caregivers whose children received coordinated ANI program care were interviewed regarding the perceived feasibility and utility of ANI program components. (3) Results: An interdisciplinary approach to a pediatric hematology/oncology population is feasible for caregivers and for providers of rehabilitation and psychosocial services within a tertiary care cancer hospital setting. Parents perceived benefits from aspects of this approach including coordinated interdisciplinary care planning, the implementation of an interdisciplinary goal, parent brain injury education, neuropsychological assessment reports, and weekly cognitive intervention sessions. Parents were interested in both having a peer mentor while managing new cancer diagnoses and later serving in a mentor role for a newly diagnosed family. (4) Conclusions: An interdisciplinary acquired brain injury approach to a pediatric hematology/oncology population is feasible with perceived benefits to families managing new cancer diagnoses. Full article
(This article belongs to the Special Issue Challenges and New Strategies in the Management of Pediatric Brain Tumors)
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22 pages, 3302 KiB  
Article
VISTA Emerges as a Promising Target against Immune Evasion Mechanisms in Medulloblastoma
by Natalia Muñoz Perez, Juliana M. Pensabene, Phillip M. Galbo, Jr., Negar Sadeghipour, Joanne Xiu, Kirsten Moziak, Rita M. Yazejian, Rachel L. Welch, W. Robert Bell, Soma Sengupta, Sonikpreet Aulakh, Charles G. Eberhart, David M. Loeb, Emad Eskandar, Deyou Zheng, Xingxing Zang and Allison M. Martin
Cancers 2024, 16(15), 2629; https://doi.org/10.3390/cancers16152629 - 24 Jul 2024
Cited by 1 | Viewed by 2322
Abstract
Background: Relapsed medulloblastoma (MB) poses a significant therapeutic challenge due to its highly immunosuppressive tumor microenvironment. Immune checkpoint inhibitors (ICIs) have struggled to mitigate this challenge, largely due to low T-cell infiltration and minimal PD-L1 expression. Identifying the mechanisms driving low T-cell infiltration [...] Read more.
Background: Relapsed medulloblastoma (MB) poses a significant therapeutic challenge due to its highly immunosuppressive tumor microenvironment. Immune checkpoint inhibitors (ICIs) have struggled to mitigate this challenge, largely due to low T-cell infiltration and minimal PD-L1 expression. Identifying the mechanisms driving low T-cell infiltration is crucial for developing more effective immunotherapies. Methods: We utilize a syngeneic mouse model to investigate the tumor immune microenvironment of MB and compare our findings to transcriptomic and proteomic data from human MB. Results: Flow cytometry reveals a notable presence of CD45hi/CD11bhi macrophage-like and CD45int/CD11bint microglia-like tumor-associated macrophages (TAMs), alongside regulatory T-cells (Tregs), expressing high levels of the inhibitory checkpoint molecule VISTA. Compared to sham control mice, the CD45hi/CD11bhi compartment significantly expands in tumor-bearing mice and exhibits a myeloid-specific signature composed of VISTA, CD80, PD-L1, CTLA-4, MHCII, CD40, and CD68. These findings are corroborated by proteomic and transcriptomic analyses of human MB samples. Immunohistochemistry highlights an abundance of VISTA-expressing myeloid cells clustering at the tumor–cerebellar border, while T-cells are scarce and express FOXP3. Additionally, tumor cells exhibit immunosuppressive properties, inhibiting CD4 T-cell proliferation in vitro. Identification of VISTA’s binding partner, VSIG8, on tumor cells, and its correlation with increased VISTA expression in human transcriptomic analyses suggests a potential therapeutic target. Conclusions: This study underscores the multifaceted mechanisms of immune evasion in MB and highlights the therapeutic potential of targeting the VISTA–VSIG axis to enhance anti-tumor responses. Full article
(This article belongs to the Special Issue Challenges and New Strategies in the Management of Pediatric Brain Tumors)
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21 pages, 1415 KiB  
Article
Proton Therapy for Advanced Juvenile Nasopharyngeal Angiofibroma
by Line Hoeltgen, Thomas Tessonnier, Eva Meixner, Philipp Hoegen, Ji-Young Kim, Maximilian Deng, Katharina Seidensaal, Thomas Held, Klaus Herfarth, Juergen Debus and Semi Harrabi
Cancers 2023, 15(20), 5022; https://doi.org/10.3390/cancers15205022 - 17 Oct 2023
Cited by 6 | Viewed by 2587
Abstract
Purpose: To provide the first report on proton radiotherapy (PRT) in the management of advanced nasopharyngeal angiofibroma (JNA) and evaluate potential benefits compared to conformal photon therapy (XRT). Methods: We retrospectively reviewed 10 consecutive patients undergoing PRT for advanced JNA in a definitive [...] Read more.
Purpose: To provide the first report on proton radiotherapy (PRT) in the management of advanced nasopharyngeal angiofibroma (JNA) and evaluate potential benefits compared to conformal photon therapy (XRT). Methods: We retrospectively reviewed 10 consecutive patients undergoing PRT for advanced JNA in a definitive or postoperative setting with a relative biological effectiveness weighted dose of 45 Gy in 25 fractions between 2012 and 2022 at the Heidelberg Ion Beam Therapy Center. Furthermore, dosimetric comparisons and risk estimations for short- and long-term radiation-induced complications between PRT plans and helical XRT plans were conducted. Results: PRT was well tolerated, with only low-grade acute toxicities (CTCAE I–II) being reported. The local control rate was 100% after a median follow-up of 27.0 (interquartile range 13.3–58.0) months. PRT resulted in considerable tumor shrinkage, leading to complete remission in five patients and bearing the potential to provide partial or complete symptom relief. Favorable dosimetric outcomes in critical brain substructures by the use of PRT translated into reduced estimated risks for neurocognitive impairment and radiation-induced CNS malignancies compared to XRT. Conclusions: PRT is an effective treatment option for advanced JNA with minimal acute morbidity and the potential for reduced radiation-induced long-term complications. Full article
(This article belongs to the Special Issue Challenges and New Strategies in the Management of Pediatric Brain Tumors)
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Review

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18 pages, 2344 KiB  
Review
Rare Oncogenic Fusions in Pediatric Central Nervous System Tumors: A Case Series and Literature Review
by Melek Ahmed, Anne Sieben, Toon Van Genechten, Sasha Libbrecht, Nathalie Gilis, Mania De Praeter, Christophe Fricx, Pierluigi Calò, Claude Van Campenhout, Nicky D’Haene, Olivier De Witte, Léon C. Van Kempen, Martin Lammens, Isabelle Salmon and Laetitia Lebrun
Cancers 2024, 16(19), 3344; https://doi.org/10.3390/cancers16193344 - 30 Sep 2024
Cited by 1 | Viewed by 1922
Abstract
Background and Objectives: Central Nervous System (CNS) pediatric tumors represent the most common solid tumors in children with a wide variability in terms of survival and therapeutic response. By contrast to their adult counterpart, the mutational landscape of pediatric CNS tumors is characterized [...] Read more.
Background and Objectives: Central Nervous System (CNS) pediatric tumors represent the most common solid tumors in children with a wide variability in terms of survival and therapeutic response. By contrast to their adult counterpart, the mutational landscape of pediatric CNS tumors is characterized by oncogenic fusions rather than multiple mutated genes. CNS pediatric tumors associated with oncogenic fusions represent a complex landscape of tumors with wide radiological, morphological and clinical heterogeneity. In the fifth CNS WHO classification, there are few pediatric CNS tumors for which diagnosis is based on a single oncogenic fusion. This work aims to provide an overview of the impact of rare oncogenic fusions (NTRK, ROS, ALK, MET, FGFR, RAF, MN1, BCOR and CIC genes) on pathogenesis, histological phenotype, diagnostics and theranostics in pediatric CNS tumors. We report four cases of pediatric CNS tumors associated with NTRK (n = 2), ROS (n = 1) and FGFR3 (n = 1) oncogenic fusion genes as a proof of concept. Cases presentation and literature review: The literature review and the cohort that we described here underline that most of these rare oncogenic fusions are not specific to a single morpho-molecular entity. Even within tumors harboring the same oncogenic fusions, a wide range of morphological, molecular and epigenetic entities can be observed. Conclusions: These findings highlight the need for caution when applying the fifth CNS WHO classification, as the vast majority of these fusions are not yet incorporated in the diagnosis, including grade evaluation and DNA methylation classification. Full article
(This article belongs to the Special Issue Challenges and New Strategies in the Management of Pediatric Brain Tumors)
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14 pages, 2264 KiB  
Review
Diffuse Midline Gliomas: Challenges and New Strategies in a Changing Clinical Landscape
by Umberto Tosi and Mark Souweidane
Cancers 2024, 16(1), 219; https://doi.org/10.3390/cancers16010219 - 2 Jan 2024
Cited by 5 | Viewed by 3915
Abstract
Diffuse intrinsic pontine glioma (DIPG) was first described by Harvey Cushing, the father of modern neurosurgery, a century ago. Since then, the classification of this tumor changed significantly, as it is now part of the broader family of diffuse midline gliomas (DMGs), a [...] Read more.
Diffuse intrinsic pontine glioma (DIPG) was first described by Harvey Cushing, the father of modern neurosurgery, a century ago. Since then, the classification of this tumor changed significantly, as it is now part of the broader family of diffuse midline gliomas (DMGs), a heterogeneous group of tumors of midline structures encompassing the entire rostro-caudal space, from the thalamus to the spinal cord. DMGs are characterized by various epigenetic events that lead to chromatin remodeling similarities, as two decades of studies made possible by increased tissue availability showed. This new understanding of tumor (epi)biology is now driving novel clinical trials that rely on targeted agents, with finally real hopes for a change in an otherwise unforgiving prognosis. This biological discovery is being paralleled with equally exciting work in therapeutic drug delivery. Invasive and noninvasive platforms have been central to early phase clinical trials with a promising safety track record and anecdotal benefits in outcome. Full article
(This article belongs to the Special Issue Challenges and New Strategies in the Management of Pediatric Brain Tumors)
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