Pediatric Cancers

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

Deadline for manuscript submissions: closed (31 December 2022) | Viewed by 68378

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Special Issue Editors

Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John’s University, New York, NY 11439, USA
Interests: pediatric cancers; neuroblastoma; cancer stem cells; metastasis; signaling pathways in cancer; immunotherapy; epigenetics; genetics; small molecule inhibitors; translational therapeutics; p53-myc interaction
Special Issues, Collections and Topics in MDPI journals
Department of Pediatrics-Oncology, Baylor College of Medicine, Houston, TX, USA
Interests: molecular mechanisms of cancer; differentiation; metastasis; neuroblastoma; target genes; therapeutic intervention; drug development

Special Issue Information

Dear Colleagues,

Childhood cancer or pediatric cancer is one of the leading causes of death among children. Treatment strategies for pediatric cancers include chemotherapy, surgery, radiation, and stem cell transplantation. These therapeutic regimens are well known to develop highly toxic and long-lasting side-effects including secondary cancers in the future lifespan of pediatric patients. Despite these intensive therapeutic regimens, cancer may still relapse as a refractory and metastatic cancer. Therefore, further understanding the causes of different pediatric cancers, mechanisms of drug-resistance, and causes of relapse and metastasis, are required for developing and advancing the less-toxic and more-effective therapeutic strategies for pediatric cancers. Recent advancements in immunotherapies and targeted therapeutic approaches using pharmacological inhibitors are one step in this direction. In this Special Issue of Cancers, we invite authors to contribute original research and review articles focusing on different aspects of pediatric cancer development, causes, maintenance, and therapeutic strategies. We will also consider articles on developmental targeted therapeutic approaches pertaining to any pediatric cancer. In this Special Issue, we will consider articles on different pediatric cancers including but not limited to, acute lymphoblastic leukemia, acute myeloid leukemia, astrocytoma, oligodendroglioma, ependymoma, choroid plexus carcinoma, oligoastrocytoma, glioblastoma, ganglioglioma, desmoplastic infantile ganglioglioma, anaplastic ganglioglioma, gangliocytoma, medulloblastoma, rhabdomyosarcoma, pineocytoma, osteosarcoma, Ewing sarcoma, neuroblastoma, Wilms tumors, retinoblastoma, non-Hodgkin lymphoma,  Hodgkin lymphoma, pleuropulmonary blastoma, hepatoblastoma, and hepatocellular carcinoma. The collected articles in this Special Issue will further enhance our knowledge and understanding of pediatric cancers and drive the development of novel therapeutic strategies.

Dr. Saurabh Agarwal
Dr. Jianhua Yang
Guest Editors

Manuscript Submission Information

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Keywords

  • Pediatric cancer
  • Immunotherapy
  • Tumorigenesis
  • Metastasis
  • Relapse
  • Small molecule inhibitors
  • Therapeutics
  • Chemotherapy

Published Papers (26 papers)

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Editorial

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4 pages, 187 KiB  
Editorial
Pediatric Cancers: Insights and Novel Therapeutic Approaches
by Saurabh Agarwal
Cancers 2023, 15(14), 3537; https://doi.org/10.3390/cancers15143537 - 08 Jul 2023
Viewed by 865
Abstract
Pediatric cancers cast a dark shadow over the lives of countless children and their families and represent a leading cause of mortality among children worldwide [...] Full article
(This article belongs to the Special Issue Pediatric Cancers)

Research

Jump to: Editorial, Review, Other

13 pages, 839 KiB  
Article
Hyperleukocytosis in Childhood Acute Leukemia: Early Complications and Survival Outcomes
by Sirinthip Kittivisuit, Nichanan Jongthitinon, Pornpun Sripornsawan, Natsaruth Songthawee, Shevachut Chavananon, Chompoonut Limratchapong, Edward B. McNeil and Thirachit Chotsampancharoen
Cancers 2023, 15(12), 3072; https://doi.org/10.3390/cancers15123072 - 06 Jun 2023
Cited by 3 | Viewed by 1502
Abstract
Hyperleukocytosis and extreme hyperleukocytosis, defined as initial white blood cell counts greater than 100 × 109/L and 200 × 109/L, respectively, have been associated with unfavorable outcomes. This study aimed to determine the early complications and survival outcomes of [...] Read more.
Hyperleukocytosis and extreme hyperleukocytosis, defined as initial white blood cell counts greater than 100 × 109/L and 200 × 109/L, respectively, have been associated with unfavorable outcomes. This study aimed to determine the early complications and survival outcomes of childhood leukemia patients with hyperleukocytosis. The medical records of 690 children newly diagnosed with acute leukemia between January 1998 and December 2017 were retrospectively reviewed. The Kaplan–Meier method and log-rank test were used to assess and compare the survival outcomes. Multivariate Cox proportional hazards regression was used to determine associated risk factors for overall survival. We found that 16.6% of 483 childhood acute lymphoblastic leukemia (ALL) patients and 20.3% of 207 childhood acute myeloid leukemia (AML) patients had hyperleukocytosis at diagnosis. ALL patients with hyperleukocytosis had more early complications than those without hyperleukocytosis (p < 0.05). Among the ALL group, the 5-year overall survival rate for those with hyperleukocytosis was significantly lower than for those without hyperleukocytosis (37.2% vs. 67.8%, p < 0.0001), while the difference was not statistically significant in the AML group (19.0% vs. 30.2%, respectively, p = 0.26). Hyperleukocytosis (hazard ratio [HR]: 2.04), extreme hyperleukocytosis (HR: 2.71), age less than 1 year (HR: 3.05), age greater than 10 years (HR: 1.64), and male sex (HR: 1.37) were independently associated with poorer overall survival in childhood ALL patients. Extreme hyperleukocytosis (HR: 2.63) and age less than 1 year (HR: 1.82) were independently associated with poorer overall survival in AML patients. Hyperleukocytosis was associated with adverse survival outcomes in childhood leukemia. Full article
(This article belongs to the Special Issue Pediatric Cancers)
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15 pages, 3044 KiB  
Article
SOX4 Mediates ATRA-Induced Differentiation in Neuroblastoma Cells
by Dongyang Zhang, Baocheng Gong, Qiang Zhao, Zhijie Li, Xiaolin Tan and Zhongyan Hua
Cancers 2022, 14(22), 5642; https://doi.org/10.3390/cancers14225642 - 17 Nov 2022
Cited by 3 | Viewed by 1558
Abstract
Neuroblastoma (NB), which is considered to be caused by the differentiation failure of neural crest cells, is the most common extracranial malignant solid tumor in children. The degree of tumor differentiation in patients with NB is closely correlated with the survival rate. To [...] Read more.
Neuroblastoma (NB), which is considered to be caused by the differentiation failure of neural crest cells, is the most common extracranial malignant solid tumor in children. The degree of tumor differentiation in patients with NB is closely correlated with the survival rate. To explore the potential targets that mediate NB cell differentiation, we analyzed four microarray datasets from GEO, and the overlapping down- or upregulated DEGs were displayed using Venn diagrams. SOX4 was one of the overlapping upregulated DEGs and was confirmed by RT-qPCR and Western blot in ATRA-treated NGP, SY5Y, and BE2 cells. To clarify whether SOX4 was the target gene regulating NB cell differentiation, the correlation between the expression of SOX4 and the survival of clinical patients was analyzed via the R2 database, SOX4 overexpression plasmids and siRNAs were generated to change the expression of SOX4, RT-qPCR and Western blot were performed to detect SOX4 expression, cell confluence or cell survival was detected by IncuCyte Zoom or CCK8 assay, immunocytochemistry staining was performed to detect cells’ neurites, and a cell cycle analysis was implemented using Flow cytometry after PI staining. The results showed that the survival probabilities were positively correlated with SOX4 expression, in which overexpressing SOX4 inhibited NB cell proliferation, elongated the cells’ neurite, and blocked the cell cycle in G1 phase, and that knockdown of the expression of SOX4 partially reversed the ATRA-induced inhibition of NB cell proliferation, the elongation of the cells’ neurites, and the blocking of the cell cycle in the G1 phase. These indicate that SOX4 may be a target to induce NB cell differentiation. Full article
(This article belongs to the Special Issue Pediatric Cancers)
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19 pages, 4815 KiB  
Article
ERK Inhibitor Ulixertinib Inhibits High-Risk Neuroblastoma Growth In Vitro and In Vivo
by Yang Yu, Yanling Zhao, Jongmin Choi, Zhongcheng Shi, Linjie Guo, John Elizarraras, Andy Gu, Feng Cheng, Yanxin Pei, Dai Lu, Muller Fabbri, Saurabh Agarwal, Chunchao Zhang, Sung Yun Jung, Jennifer H. Foster and Jianhua Yang
Cancers 2022, 14(22), 5534; https://doi.org/10.3390/cancers14225534 - 10 Nov 2022
Cited by 3 | Viewed by 2371
Abstract
Neuroblastoma (NB) is a pediatric tumor of the peripheral nervous system. Approximately 80% of relapsed NB show RAS-MAPK pathway mutations that activate ERK, resulting in the promotion of cell proliferation and drug resistance. Ulixertinib, a first-in-class ERK-specific inhibitor, has shown promising antitumor activity [...] Read more.
Neuroblastoma (NB) is a pediatric tumor of the peripheral nervous system. Approximately 80% of relapsed NB show RAS-MAPK pathway mutations that activate ERK, resulting in the promotion of cell proliferation and drug resistance. Ulixertinib, a first-in-class ERK-specific inhibitor, has shown promising antitumor activity in phase 1 clinical trials for advanced solid tumors. Here, we show that ulixertinib significantly and dose-dependently inhibits cell proliferation and colony formation in different NB cell lines, including PDX cells. Transcriptomic analysis revealed that ulixertinib extensively inhibits different oncogenic and neuronal developmental pathways, including EGFR, VEGF, WNT, MAPK, NGF, and NTRK1. The proteomic analysis further revealed that ulixertinib inhibits the cell cycle and promotes apoptosis in NB cells. Additionally, ulixertinib treatment significantly sensitized NB cells to the conventional chemotherapeutic agent doxorubicin. Furthermore, ulixertinib potently inhibited NB tumor growth and prolonged the overall survival of the treated mice in two different NB mice models. Our preclinical study demonstrates that ulixertinib, either as a single agent or in combination with current therapies, is a novel and practical therapeutic approach for NB. Full article
(This article belongs to the Special Issue Pediatric Cancers)
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16 pages, 4269 KiB  
Article
Reduction of LPAR1 Expression in Neuroblastoma Promotes Tumor Cell Migration
by Xiangjun Liu, Mengmiao Pei, Yongbo Yu, Xiaolin Wang and Jingang Gui
Cancers 2022, 14(14), 3346; https://doi.org/10.3390/cancers14143346 - 09 Jul 2022
Cited by 2 | Viewed by 1867
Abstract
Neuroblastoma is the most common extracranial solid tumor in children. Tumor metastasis in high-risk NB patients is an essential problem that impairs the survival of patients. In this study, we aimed to use a comprehensive bioinformatics analysis to identify differentially expressed genes between [...] Read more.
Neuroblastoma is the most common extracranial solid tumor in children. Tumor metastasis in high-risk NB patients is an essential problem that impairs the survival of patients. In this study, we aimed to use a comprehensive bioinformatics analysis to identify differentially expressed genes between NB and control cells, and to explore novel prognostic markers or treatment targets in tumors. In this way, FN1, PIK3R5, LPAR6 and LPAR1 were screened out via KEGG, GO and PPI network analysis, and we verified the expression and function of LPAR1 experimentally. Our research verified the decreased expression of LPAR1 in NB cells, and the tumor migration inhibitory effects of LPA on NB cells via LPAR1. Moreover, knockdown of LPAR1 promoted NB cell migration and abolished the migration-inhibitory effects mediated by LPA-LPAR1. The tumor-suppressing effects of the LPA-LPAR1 axis suggest that LPAR1 might be a potential target for future treatment of NB. Full article
(This article belongs to the Special Issue Pediatric Cancers)
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13 pages, 4879 KiB  
Article
Dual Targeting of PI3K and HDAC by CUDC-907 Inhibits Pediatric Neuroblastoma Growth
by Rameswari Chilamakuri and Saurabh Agarwal
Cancers 2022, 14(4), 1067; https://doi.org/10.3390/cancers14041067 - 20 Feb 2022
Cited by 15 | Viewed by 3165
Abstract
The dysregulation of PI3K, HDACs, and MYCN are well known for promoting multiple cancer types, including neuroblastoma (NB). Targeting the upstream regulators of MYCN, including HDACs and PI3K, was shown to suppress cancer growth. In the present study, we analyze different NB patient [...] Read more.
The dysregulation of PI3K, HDACs, and MYCN are well known for promoting multiple cancer types, including neuroblastoma (NB). Targeting the upstream regulators of MYCN, including HDACs and PI3K, was shown to suppress cancer growth. In the present study, we analyze different NB patient datasets to reveal that high PI3K and HDAC expression is correlated with overall poor NB patient survival. High PI3K level is also found to be associated with high MYCN level and NB stage progression. We repurpose a dual inhibitor CUDC-907 as a single agent to directly target both PI3K and HDAC in NB. We use in vitro methodologies to determine the efficacy and selectivity of CUDC-907 using six NB and three control fibroblast cell lines. Our results show that CUDC-907 significantly inhibits NB proliferation and colony growth, induces apoptosis, blocks cell cycle progression, inhibits MYCN, and enhances H3K9Ac levels by inhibiting the PI3K/AKT signaling pathway and HDAC function. Furthermore, CUDC-907 significantly inhibits NB tumor growth in a 3D spheroid tumor model that recapitulates the in vivo tumor growth. Overall, our findings highlight that the dual inhibition of PI3K and HDAC by CUDC-907 is an effective therapeutic strategy for NB and other MYC-dependent cancers. Full article
(This article belongs to the Special Issue Pediatric Cancers)
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15 pages, 1895 KiB  
Article
The Effect of Direct and Indirect EZH2 Inhibition in Rhabdomyosarcoma Cell Lines
by Andreas Schmidt, Lucas Behrendt, Jana Eybe, Steven W. Warmann, Sabine Schleicher, Joerg Fuchs and Evi Schmid
Cancers 2022, 14(1), 41; https://doi.org/10.3390/cancers14010041 - 23 Dec 2021
Cited by 5 | Viewed by 2734
Abstract
Enhancer of Zeste homolog 2 (EZH2) is involved in epigenetic regulation of gene transcription by catalyzing trimethylation of histone 3 at lysine 27. In rhabdomyosarcoma (RMS), increased EZH2 protein levels are associated with poor prognosis and increased metastatic potential, suggesting EZH2 as a [...] Read more.
Enhancer of Zeste homolog 2 (EZH2) is involved in epigenetic regulation of gene transcription by catalyzing trimethylation of histone 3 at lysine 27. In rhabdomyosarcoma (RMS), increased EZH2 protein levels are associated with poor prognosis and increased metastatic potential, suggesting EZH2 as a therapeutic target. The inhibition of EZH2 can be achieved by direct inhibition which targets only the enzyme activity or by indirect inhibition which also affects activities of other methyltransferases and reduces EZH2 protein abundance. We assessed the direct inhibition of EZH2 by EPZ005687 and the indirect inhibition by 3-deazaneplanocin (DZNep) and adenosine dialdehyde (AdOx) in the embryonal RD and the alveolar RH30 RMS cell line. EPZ005687 was more effective in reducing the cell viability and colony formation, in promoting apoptosis induction, and in arresting cells in the G1 phase of the cell cycle than the indirect inhibitors. DZNep was more effective in decreasing spheroid viability and size in both cell lines than EPZ005687 and AdOx. Both types of inhibitors reduced cell migration of RH30 cells but not of RD cells. The results show that direct and indirect inhibition of EZH2 affect cellular functions differently. The alveolar cell line RH30 is more sensitive to epigenetic intervention than the embryonal cell line RD. Full article
(This article belongs to the Special Issue Pediatric Cancers)
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22 pages, 3041 KiB  
Article
Altertoxin II, a Highly Effective and Specific Compound against Ewing Sarcoma
by Andrew J. Robles, Wentao Dai, Saikat Haldar, Hongyan Ma, Victoria M. Anderson, Ross D. Overacker, April L. Risinger, Sandra Loesgen, Peter J. Houghton, Robert H. Cichewicz and Susan L. Mooberry
Cancers 2021, 13(24), 6176; https://doi.org/10.3390/cancers13246176 - 07 Dec 2021
Cited by 5 | Viewed by 3113
Abstract
A screening program designed to identify natural products with selective cytotoxic effects against cell lines representing different types of pediatric solid tumors led to the identification of altertoxin II as a highly potent and selective cytotoxin against Ewing sarcoma cell lines. Altertoxin II, [...] Read more.
A screening program designed to identify natural products with selective cytotoxic effects against cell lines representing different types of pediatric solid tumors led to the identification of altertoxin II as a highly potent and selective cytotoxin against Ewing sarcoma cell lines. Altertoxin II, but not the related compounds altertoxin I and alteichin, was highly effective against every Ewing sarcoma cell line tested, with an average 25-fold selectivity for these cells as compared to cells representing other pediatric and adult cancers. Mechanism of action studies revealed that altertoxin II causes DNA double-strand breaks, a rapid DNA damage response, and cell cycle accumulation in the S phase. Our studies also demonstrate that the potent effects of altertoxin II are partially dependent on the progression through the cell cycle, because the G1 arrest initiated by a CDK4/6 inhibitor decreased antiproliferative potency more than 10 times. Importantly, the cell-type-selective DNA-damaging effects of altertoxin II in Ewing sarcoma cells occur independently of its ability to bind directly to DNA. Ultimately, we found that altertoxin II has a dose-dependent in vivo antitumor efficacy against a Ewing sarcoma xenograft, suggesting that it has potential as a therapeutic drug lead and will be useful to identify novel targets for Ewing-sarcoma-specific therapies. Full article
(This article belongs to the Special Issue Pediatric Cancers)
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17 pages, 5647 KiB  
Article
EWSR1-WT1 Target Genes and Therapeutic Options Identified in a Novel DSRCT In Vitro Model
by Margit Bleijs, Corine Pleijte, Sem Engels, Femke Ringnalda, Friederike Meyer-Wentrup, Marc van de Wetering and Hans Clevers
Cancers 2021, 13(23), 6072; https://doi.org/10.3390/cancers13236072 - 02 Dec 2021
Cited by 6 | Viewed by 2715
Abstract
Desmoplastic small round cell tumor (DSRCT) is a rare and aggressive soft tissue sarcoma with a lack of effective treatment options and a poor prognosis. DSRCT is characterized by a chromosomal translocation, resulting in the EWSR1-WT1 gene fusion. The molecular mechanisms driving DSRCT [...] Read more.
Desmoplastic small round cell tumor (DSRCT) is a rare and aggressive soft tissue sarcoma with a lack of effective treatment options and a poor prognosis. DSRCT is characterized by a chromosomal translocation, resulting in the EWSR1-WT1 gene fusion. The molecular mechanisms driving DSRCT are poorly understood, and a paucity of preclinical models hampers DSRCT research. Here, we establish a novel primary patient-derived DSRCT in vitro model, recapitulating the original tumor. We find that EWSR1-WT1 expression affects cell shape and cell survival, and we identify downstream target genes of the EWSR1-WT1 fusion. Additionally, this preclinical in vitro model allows for medium-throughput drug screening. We discover sensitivity to several drugs, including compounds targeting RTKs. MERTK, which has been described as a therapeutic target for several malignancies, correlates with EWSR1-WT1 expression. Inhibition of MERTK with the small-molecule inhibitor UNC2025 results in reduced proliferation of DSRCT cells in vitro, suggesting MERTK as a therapeutic target in DSRCT. This study underscores the usefulness of preclinical in vitro models for studying molecular mechanisms and potential therapeutic options. Full article
(This article belongs to the Special Issue Pediatric Cancers)
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12 pages, 1476 KiB  
Article
Characteristics of Nephroblastoma/Nephroblastomatosis in Children with a Clinically Reported Underlying Malformation or Cancer Predisposition Syndrome
by Nils Welter, Angelo Wagner, Rhoikos Furtwängler, Patrick Melchior, Leo Kager, Christian Vokuhl, Jens-Peter Schenk, Clemens Magnus Meier, Stefan Siemer, Manfred Gessler and Norbert Graf
Cancers 2021, 13(19), 5016; https://doi.org/10.3390/cancers13195016 - 07 Oct 2021
Cited by 8 | Viewed by 2556 | Correction
Abstract
(1) Background: about 10% of Wilms Tumor (WT) patients have a malformation or cancer predisposition syndrome (CPS) with causative germline genetic or epigenetic variants. Knowledge on CPS is essential for genetic counselling. (2) Methods: this retrospective analysis focused on 2927 consecutive patients with [...] Read more.
(1) Background: about 10% of Wilms Tumor (WT) patients have a malformation or cancer predisposition syndrome (CPS) with causative germline genetic or epigenetic variants. Knowledge on CPS is essential for genetic counselling. (2) Methods: this retrospective analysis focused on 2927 consecutive patients with WTs registered between 1989 and 2017 in the SIOP/GPOH studies. (3) Results: Genitourinary malformations (GU, N = 66, 2.3%), Beckwith-Wiedemann spectrum (BWS, N = 32, 1.1%), isolated hemihypertrophy (IHH, N = 29, 1.0%), Denys-Drash syndrome (DDS, N = 24, 0.8%) and WAGR syndrome (N = 20, 0.7%) were reported most frequently. Compared to others, these patients were younger at WT diagnosis (median age 24.5 months vs. 39.0 months), had smaller tumors (349.4 mL vs. 487.5 mL), less often metastasis (8.2% vs. 18%), but more often nephroblastomatosis (12.9% vs. 1.9%). WT with IHH was associated with blastemal WT and DDS with stromal subtype. Bilateral WTs were common in WAGR (30%), DDS (29%) and BWS (31%). Chemotherapy induced reduction in tumor volume was poor in DDS (0.4% increase) and favorable in BWS (86.9% reduction). The event-free survival (EFS) of patients with BWS was significantly (p = 0.002) worse than in others. (4) Conclusions: CPS should be considered in WTs with specific clinical features resulting in referral to a geneticist. Their outcome was not always favorable. Full article
(This article belongs to the Special Issue Pediatric Cancers)
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20 pages, 2283 KiB  
Article
Surfaceome Profiling of Rhabdomyosarcoma Reveals B7-H3 as a Mediator of Immune Evasion
by Roxane R. Lavoie, Patricio C. Gargollo, Mohamed E. Ahmed, Yohan Kim, Emily Baer, Doris A. Phelps, Cristine M. Charlesworth, Benjamin J. Madden, Liguo Wang, Peter J. Houghton, John Cheville, Haidong Dong, Candace F. Granberg and Fabrice Lucien
Cancers 2021, 13(18), 4528; https://doi.org/10.3390/cancers13184528 - 09 Sep 2021
Cited by 11 | Viewed by 3338
Abstract
Novel therapeutic strategies are needed for the treatment of rhabdomyosarcoma (RMS), the most common soft-tissue sarcoma in children. By using a combination of cell surface proteomics and transcriptomic profiling of RMS and normal muscle, we generated a catalog of targetable cell surface proteins [...] Read more.
Novel therapeutic strategies are needed for the treatment of rhabdomyosarcoma (RMS), the most common soft-tissue sarcoma in children. By using a combination of cell surface proteomics and transcriptomic profiling of RMS and normal muscle, we generated a catalog of targetable cell surface proteins enriched in RMS tumors. Among the top candidates, we identified B7-H3 as the major immunoregulatory molecule expressed by RMS tumors. By using a large cohort of tissue specimens, we demonstrated that B7-H3 is expressed in a majority of RMS tumors while not detected in normal human tissues. Through a deconvolution analysis of the RMS tumor RNA-seq data, we showed that B7-H3-rich tumors are enriched in macrophages M1, NK cells, and depleted in CD8+-T cells. Furthermore, in vitro functional assays showed that B7-H3 knockout in RMS tumor cells increases T-cell mediated cytotoxicity. Altogether, our study uncovers new potential targets for the treatment of RMS and provides the first biological insights into the role of B7-H3 in RMS biology, paving the way for the development of next-generation immunotherapies. Full article
(This article belongs to the Special Issue Pediatric Cancers)
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14 pages, 1882 KiB  
Article
Somatic Disease in Survivors of Childhood Malignant Bone Tumors in the Nordic Countries
by Camilla Pedersen, Catherine Rechnitzer, Elisabeth Anne Wreford Andersen, Line Kenborg, Filippa Nyboe Norsker, Andrea Bautz, Thomas Baad-Hansen, Laufey Tryggvadottir, Laura-Maria Madanat-Harjuoja, Anna Sällfors Holmqvist, Lars Hjorth, Henrik Hasle, Jeanette Falck Winther and on behalf of the ALiCCS Study Group
Cancers 2021, 13(18), 4505; https://doi.org/10.3390/cancers13184505 - 07 Sep 2021
Cited by 3 | Viewed by 1704
Abstract
Survivors of malignant bone tumors in childhood are at risk of long-term adverse health effects. We comprehensively reviewed cases of somatic diseases that required a hospital contact in survivors of osteosarcoma and Ewing sarcoma. In a population-based cohort study, 620 five-year survivors of [...] Read more.
Survivors of malignant bone tumors in childhood are at risk of long-term adverse health effects. We comprehensively reviewed cases of somatic diseases that required a hospital contact in survivors of osteosarcoma and Ewing sarcoma. In a population-based cohort study, 620 five-year survivors of osteosarcoma (n = 440) or Ewing sarcoma (n = 180), diagnosed before the age of 20 years in Denmark, Finland, Iceland, and Sweden during 1943–2008, were followed in the national hospital registers. Overall rates of hospital contacts for any somatic disease and for 12 main diagnostic groups and 120 specific disease categories were compared with those in a matched comparison cohort (n = 3049) randomly selected from the national population registers. The rate of hospital contact for any somatic disease was 80% higher in survivors of malignant bone tumors than in comparisons and remained elevated up to 30 years after diagnosis. The rate of hospital contacts was higher after Ewing sarcoma (rate ratio (RR) 2.24; 95% confidence interval (CI) 1.76–2.85) than after osteosarcoma (RR 1.67; 95% CI 1.41–1.98). Elevated rates were observed for 11 main diagnostic groups, including infections, second malignant neoplasms, and diseases of the skin, bones, and circulatory, digestive, endocrine, and urinary systems. Survivors of malignant bone tumors in childhood are at increased risk of somatic diseases many years after diagnosis. This comprehensive study contributes new insight into the risk of late effects in survivors of osteosarcoma and Ewing sarcoma, which is an essential basis for optimal patient counseling and follow-up care. Full article
(This article belongs to the Special Issue Pediatric Cancers)
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15 pages, 4212 KiB  
Article
Identification of an RNA-Binding-Protein-Based Prognostic Model for Ewing Sarcoma
by Yi Chen, Huafang Su, Yanhong Su, Yifan Zhang, Yingbo Lin and Felix Haglund
Cancers 2021, 13(15), 3736; https://doi.org/10.3390/cancers13153736 - 25 Jul 2021
Cited by 7 | Viewed by 2202
Abstract
RNA-binding proteins (RBPs) are important transcriptomic regulators and may be important in tumorigenesis. Here, we sought to investigate the clinical impact of RBPs for patients with Ewing sarcoma (ES). ES transcriptome signatures were characterized from four previously published cohorts and grouped into new [...] Read more.
RNA-binding proteins (RBPs) are important transcriptomic regulators and may be important in tumorigenesis. Here, we sought to investigate the clinical impact of RBPs for patients with Ewing sarcoma (ES). ES transcriptome signatures were characterized from four previously published cohorts and grouped into new training and validation cohorts. A total of three distinct subtypes were identified and compared for differences in patient prognosis and RBP signatures. Next, univariate Cox and Lasso regression models were used to identify hub prognosis-related RBPs and construct a prognostic risk model, and prediction capacity was assessed through time-dependent receiver operating characteristics (ROCs), Kaplan–Meier curves, and nomograms. Across the three RBP subtypes, 29 significant prognostic-associated RBP genes were identified, of which 10 were used to build and validate an RBP-associated prognostic risk model (RPRM) that had a stable predictive value and could be considered valuable for clinical risk-stratification of ES. A comparison with immunohistochemistry validation showed a significant association between overall survival and NSUN7 immunoreactivity, which was an independent favorable prognostic marker. The association of RBP signatures with ES clinical prognosis provides a strong rationale for further investigation into RBPs molecular mechanisms. Full article
(This article belongs to the Special Issue Pediatric Cancers)
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13 pages, 3110 KiB  
Article
Oral Metronomic Maintenance Therapy Can Improve Survival in High-Risk Neuroblastoma Patients Not Treated with ASCT or Anti-GD2 Antibodies
by Xiaofei Sun, Zijun Zhen, Ying Guo, Yuanhong Gao, Juan Wang, Yu Zhang, Jia Zhu, Suying Lu, Feifei Sun, Junting Huang, Ruiqing Cai, Yizhuo Zhang, Juncheng Liu, Zizheng Xiao, Sihui Zeng and Zhuowei Liu
Cancers 2021, 13(14), 3494; https://doi.org/10.3390/cancers13143494 - 13 Jul 2021
Cited by 5 | Viewed by 2123
Abstract
Despite aggressive treatment, the prognosis of high-risk NB patients is still poor. This retrospective study investigated the benefits of metronomic maintenance treatment (MT) in high-risk NB patients without ASCT or GD2 antibody therapy. Patients aged ≤ 21 years with newly diagnosed high-risk NB [...] Read more.
Despite aggressive treatment, the prognosis of high-risk NB patients is still poor. This retrospective study investigated the benefits of metronomic maintenance treatment (MT) in high-risk NB patients without ASCT or GD2 antibody therapy. Patients aged ≤ 21 years with newly diagnosed high-risk NB were included. Patients with complete/very good partial remission (CR/VGPR/PR) to conventional treatment received, or not, oral metronomic MT for 1 year. Two hundred and seventeen high-risk NB patients were enrolled. One hundred and eighty-five (85%) had a CR/VGPR/PR to conventional treatment, of the patients with stage 4, 106 receiving and 61 not receiving oral metronomic MT, and the 3-year event-free survival (EFS) rate was 42.5 ± 5.1% and 29.6 ± 6%, respectively (p = 0.017), and overall survival (OS) rate was 71.1 ± 4.7% and 59.4 ± 6.4%, respectively (p = 0.022). A total of 117 high-risk patients with oral metronomic MT had EFS rate of 42.7 ± 4.8%. The toxicity of MT was mild. For high-risk NB patients without ASCT or anti-GD2 antibody therapy, stage 4, MYCN amplication and patients with stage 4 not receiving oral metronomic MT after CR/VGPR/PR were independent adverse prognostic factors. Oral metronomic MT can improve survival in high-risk NB patients in CR/VGPR/PR without ASCT or anti-GD2 antibodies therapy. Full article
(This article belongs to the Special Issue Pediatric Cancers)
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21 pages, 2716 KiB  
Article
Serine-Threonine Kinase Receptor-Associated Protein (STRAP) Knockout Decreases the Malignant Phenotype in Neuroblastoma Cell Lines
by Laura V Bownes, Adele P Williams, Raoud Marayati, Colin H Quinn, Sara C Hutchins, Jerry E Stewart, Trung Vu, Juliet L Easlick, Elizabeth Mroczek-Musulman, David K Crossman, Joshua C Anderson, Christopher D Willey, Pran K Datta and Elizabeth A Beierle
Cancers 2021, 13(13), 3201; https://doi.org/10.3390/cancers13133201 - 26 Jun 2021
Cited by 7 | Viewed by 2264
Abstract
Background: Serine-threonine kinase receptor-associated protein (STRAP) plays an important role in neural development but also in tumor growth. Neuroblastoma, a tumor of neural crest origin, is the most common extracranial solid malignancy of childhood and it continues to carry a poor prognosis. The [...] Read more.
Background: Serine-threonine kinase receptor-associated protein (STRAP) plays an important role in neural development but also in tumor growth. Neuroblastoma, a tumor of neural crest origin, is the most common extracranial solid malignancy of childhood and it continues to carry a poor prognosis. The recent discovery of the role of STRAP in another pediatric solid tumor, osteosarcoma, and the known function of STRAP in neural development, led us to investigate the role of STRAP in neuroblastoma tumorigenesis. Methods: STRAP protein expression was abrogated in two human neuroblastoma cell lines, SK-N-AS and SK-N-BE(2), using transient knockdown with siRNA, stable knockdown with shRNA lentiviral transfection, and CRISPR-Cas9 genetic knockout. STRAP knockdown and knockout cells were examined for phenotypic alterations in vitro and tumor growth in vivo. Results: Cell proliferation, motility, and growth were significantly decreased in STRAP knockout compared to wild-type cells. Indicators of stemness, including mRNA abundance of common stem cell markers Oct4, Nanog, and Nestin, the percentage of cells expressing CD133 on their surface, and the ability to form tumorspheres were significantly decreased in the STRAP KO cells. In vivo, STRAP knockout cells formed tumors less readily than wild-type tumor cells. Conclusion: These novel findings demonstrated that STRAP plays a role in tumorigenesis and maintenance of neuroblastoma stemness. Full article
(This article belongs to the Special Issue Pediatric Cancers)
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11 pages, 7641 KiB  
Article
Preliminary Radiogenomic Evidence for the Prediction of Metastasis and Chemotherapy Response in Pediatric Patients with Osteosarcoma Using 18F-FDG PET/CT, EZRIN, and KI67
by Byung-Chul Kim, Jingyu Kim, Kangsan Kim, Byung Hyun Byun, Ilhan Lim, Chang-Bae Kong, Won Seok Song, Jae-Soo Koh and Sang-Keun Woo
Cancers 2021, 13(11), 2671; https://doi.org/10.3390/cancers13112671 - 28 May 2021
Cited by 12 | Viewed by 2807
Abstract
Chemotherapy response and metastasis prediction play important roles in the treatment of pediatric osteosarcoma, which is prone to metastasis and has a high mortality rate. This study aimed to estimate the prediction model using gene expression and image texture features. 18F-fluorodeoxyglucose positron emission [...] Read more.
Chemotherapy response and metastasis prediction play important roles in the treatment of pediatric osteosarcoma, which is prone to metastasis and has a high mortality rate. This study aimed to estimate the prediction model using gene expression and image texture features. 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) images of 52 pediatric osteosarcoma patients were used to estimate the machine learning algorithm. An appropriate algorithm was selected by estimating the machine learning accuracy. 18F-FDG PET/CT images of 21 patients were selected for prediction model development based on simultaneous KI67 and EZRIN expression. The prediction model for chemotherapy response and metastasis was estimated using area under the curve (AUC) maximum image texture features (AUC_max) and gene expression. The machine learning algorithm with the highest test accuracy in chemotherapy response and metastasis was selected using the random forest algorithm. The chemotherapy response and metastasis test accuracy with image texture features was 0.83 and 0.76, respectively. The highest test accuracy and AUC of chemotherapy response with AUC_max, KI67, and EZRIN were estimated to be 0.85 and 0.89, respectively. The highest test accuracy and AUC of metastasis with AUC_max, KI67, and EZRIN were estimated to be 0.85 and 0.8, respectively. The metastasis prediction accuracy increased by 10% using radiogenomics data. Full article
(This article belongs to the Special Issue Pediatric Cancers)
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13 pages, 288 KiB  
Article
Infectious Morbidity in Pediatric Patients Receiving Neoadjuvant Chemotherapy for Sarcoma
by Denise Willmer, Stefan K. Zöllner, Frieder Schaumburg, Heribert Jürgens, Thomas Lehrnbecher and Andreas H. Groll
Cancers 2021, 13(9), 1990; https://doi.org/10.3390/cancers13091990 - 21 Apr 2021
Cited by 8 | Viewed by 1983
Abstract
The purpose of this retrospective, single-center cohort study was to assess the infectious burden in pediatric sarcoma patients during neoadjuvant chemotherapy. The review included all patients with a new diagnosis of Ewing sarcoma, osteosarcoma or soft tissue sarcoma between September 2009 and December [...] Read more.
The purpose of this retrospective, single-center cohort study was to assess the infectious burden in pediatric sarcoma patients during neoadjuvant chemotherapy. The review included all patients with a new diagnosis of Ewing sarcoma, osteosarcoma or soft tissue sarcoma between September 2009 and December 2018 who were enrolled in the EWING 2008, CWS SoTiSaR and EURAMOS clinical trial or registry. Primary endpoints were the occurrence of febrile neutropenia (FN) and microbiologically documented infection (MDI). Parameters with a potential impact on FN and MDI were also analyzed. A total of 170 sarcoma patients (median age: 13 years, range: 0–21; 96 m/74 f) received 948 chemotherapy courses (median: 6; range: 2–8). Of these patients, 58.8% had ≥1 FN episode and 20.6% ≥ 1 MDI. FN occurred in 272/948 courses (28.7%) with fever of unknown origin (FUO) in 231 courses and 45 MDI and 19 clinically documented infections (CDI) occurring in a total of 57 courses. Patients enrolled in EWING 2008 had significantly more FN (p < 0.001), infections (p = 0.02) and MDI (p = 0.035). No infection-related deaths were observed. Younger age, tumor type and localization, and higher median and maximum mucositis grades were significantly associated with higher numbers of FN (p < 0.001), and younger age (p = 0.024) and higher median mucositis grade (p = 0.017) with MDI. The study shows substantial infectious morbidity in sarcoma patients during neoadjuvant chemotherapy treatment and opportunities to improve prevention and management. Full article
(This article belongs to the Special Issue Pediatric Cancers)

Review

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17 pages, 1063 KiB  
Review
The Battlefield of Chemotherapy in Pediatric Cancers
by Letao Bo, Youyou Wang, Yidong Li, John N. D. Wurpel, Zoufang Huang and Zhe-Sheng Chen
Cancers 2023, 15(7), 1963; https://doi.org/10.3390/cancers15071963 - 24 Mar 2023
Cited by 5 | Viewed by 1699
Abstract
The survival rate for pediatric cancers has remarkably improved in recent years. Conventional chemotherapy plays a crucial role in treating pediatric cancers, especially in low- and middle-income countries where access to advanced treatments may be limited. The Food and Drug Administration (FDA) approved [...] Read more.
The survival rate for pediatric cancers has remarkably improved in recent years. Conventional chemotherapy plays a crucial role in treating pediatric cancers, especially in low- and middle-income countries where access to advanced treatments may be limited. The Food and Drug Administration (FDA) approved chemotherapy drugs that can be used in children have expanded, but patients still face numerous side effects from the treatment. In addition, multidrug resistance (MDR) continues to pose a major challenge in improving the survival rates for a significant number of patients. This review focuses on the severe side effects of pediatric chemotherapy, including doxorubicin-induced cardiotoxicity (DIC) and vincristine-induced peripheral neuropathy (VIPN). We also delve into the mechanisms of MDR in chemotherapy to the improve survival and reduce the toxicity of treatment. Additionally, the review focuses on various drug transporters found in common types of pediatric tumors, which could offer different therapeutic options. Full article
(This article belongs to the Special Issue Pediatric Cancers)
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19 pages, 2158 KiB  
Review
Pediatric Myeloid Sarcoma, More than Just a Chloroma: A Review of Clinical Presentations, Significance, and Biology
by Kristin E. Zorn, Ashley M. Cunningham, Alison E. Meyer, Karen Sue Carlson and Sridhar Rao
Cancers 2023, 15(5), 1443; https://doi.org/10.3390/cancers15051443 - 24 Feb 2023
Cited by 4 | Viewed by 2029
Abstract
Myeloid sarcomas (MS), commonly referred to as chloromas, are extramedullary tumors of acute myeloid leukemia (AML) with varying incidence and influence on outcomes. Pediatric MS has both a higher incidence and unique clinical presentation, cytogenetic profile, and set of risk factors compared to [...] Read more.
Myeloid sarcomas (MS), commonly referred to as chloromas, are extramedullary tumors of acute myeloid leukemia (AML) with varying incidence and influence on outcomes. Pediatric MS has both a higher incidence and unique clinical presentation, cytogenetic profile, and set of risk factors compared to adult patients. Optimal treatment remains undefined, yet allogeneic hematopoietic stem cell transplantation (allo-HSCT) and epigenetic reprogramming in children are potential therapies. Importantly, the biology of MS development is poorly understood; however, cell-cell interactions, epigenetic dysregulation, cytokine signaling, and angiogenesis all appear to play key roles. This review describes pediatric-specific MS literature and the current state of knowledge about the biological determinants that drive MS development. While the significance of MS remains controversial, the pediatric experience provides an opportunity to investigate mechanisms of disease development to improve patient outcomes. This brings the hope of better understanding MS as a distinct disease entity deserving directed therapeutic approaches. Full article
(This article belongs to the Special Issue Pediatric Cancers)
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18 pages, 1947 KiB  
Review
Immune Microenvironment and Immunotherapies for Diffuse Intrinsic Pontine Glioma
by Yujia Chen, Chao Zhao, Shenglun Li, Jun Wang and Hongwei Zhang
Cancers 2023, 15(3), 602; https://doi.org/10.3390/cancers15030602 - 18 Jan 2023
Cited by 10 | Viewed by 2331
Abstract
Diffuse intrinsic pontine glioma (DIPG) is a primary glial glioma that occurs in all age groups but predominates in children and is the main cause of solid tumor-related childhood mortality. Due to its rapid progression, the inability to operate and insensitivity to most [...] Read more.
Diffuse intrinsic pontine glioma (DIPG) is a primary glial glioma that occurs in all age groups but predominates in children and is the main cause of solid tumor-related childhood mortality. Due to its rapid progression, the inability to operate and insensitivity to most chemotherapies, there is a lack of effective treatment methods in clinical practice for DIPG patients. The prognosis of DIPG patients is extremely poor, with a median survival time of no more than 12 months. In recent years, there have been continuous breakthroughs for immunotherapies in various hematological tumors and malignant solid tumors with extremely poor prognoses, which provides new insights into tumors without effective treatment strategies. Meanwhile, with the gradual development of stereotactic biopsy techniques, it is gradually becoming easier and safer to obtain live DIPG tissue, and the understanding of the immune properties of DIPG has also increased. On this basis, a series of immunotherapy studies of DIPG are under way, some of which have shown encouraging results. Herein, we review the current understanding of the immune characteristics of DIPG and critically reveal the limitations of current immune research, as well as the opportunities and challenges for immunological therapies in DIPG, hoping to clarify the development of novel immunotherapies for DIPG treatment. Full article
(This article belongs to the Special Issue Pediatric Cancers)
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28 pages, 2665 KiB  
Review
Childhood Malignant Brain Tumors: Balancing the Bench and Bedside
by Colin Thorbinson and John-Paul Kilday
Cancers 2021, 13(23), 6099; https://doi.org/10.3390/cancers13236099 - 03 Dec 2021
Cited by 15 | Viewed by 3341
Abstract
Brain tumors are the leading cause of childhood cancer deaths in developed countries. They also represent the most common solid tumor in this age group, accounting for approximately one-quarter of all pediatric cancers. Developments in neuro-imaging, neurosurgical techniques, adjuvant therapy and supportive care [...] Read more.
Brain tumors are the leading cause of childhood cancer deaths in developed countries. They also represent the most common solid tumor in this age group, accounting for approximately one-quarter of all pediatric cancers. Developments in neuro-imaging, neurosurgical techniques, adjuvant therapy and supportive care have improved survival rates for certain tumors, allowing a future focus on optimizing cure, whilst minimizing long-term adverse effects. Recent times have witnessed a rapid evolution in the molecular characterization of several of the common pediatric brain tumors, allowing unique clinical and biological patient subgroups to be identified. However, a resulting paradigm shift in both translational therapy and subsequent survival for many of these tumors remains elusive, while recurrence remains a great clinical challenge. This review will provide an insight into the key molecular developments and global co-operative trial results for the most common malignant pediatric brain tumors (medulloblastoma, high-grade gliomas and ependymoma), highlighting potential future directions for management, including novel therapeutic options, and critical challenges that remain unsolved. Full article
(This article belongs to the Special Issue Pediatric Cancers)
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23 pages, 12896 KiB  
Review
Molecular Stratification of Childhood Ependymomas as a Basis for Personalized Diagnostics and Treatment
by Margarita Zaytseva, Ludmila Papusha, Galina Novichkova and Alexander Druy
Cancers 2021, 13(19), 4954; https://doi.org/10.3390/cancers13194954 - 01 Oct 2021
Cited by 6 | Viewed by 7232
Abstract
Ependymomas are among the most enigmatic tumors of the central nervous system, posing enormous challenges for pathologists and clinicians. Despite the efforts made, the treatment options are still limited to surgical resection and radiation therapy, while none of conventional chemotherapies is beneficial. While [...] Read more.
Ependymomas are among the most enigmatic tumors of the central nervous system, posing enormous challenges for pathologists and clinicians. Despite the efforts made, the treatment options are still limited to surgical resection and radiation therapy, while none of conventional chemotherapies is beneficial. While being histologically similar, ependymomas show considerable clinical and molecular diversity. Their histopathological evaluation alone is not sufficient for reliable diagnostics, prognosis, and choice of treatment strategy. The importance of integrated diagnosis for ependymomas is underscored in the recommendations of Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy. These updated recommendations were adopted and implemented by WHO experts. This minireview highlights recent advances in comprehensive molecular-genetic characterization of ependymomas. Strong emphasis is made on the use of molecular approaches for verification and specification of histological diagnoses, as well as identification of prognostic markers for ependymomas in children. Full article
(This article belongs to the Special Issue Pediatric Cancers)
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23 pages, 1095 KiB  
Review
The Psychoneuroimmunology of Stress Regulation in Pediatric Cancer Patients
by Gillian E. White, Jessica E. Caterini, Victoria McCann, Kate Rendall, Paul C. Nathan, Shawn G. Rhind, Heather Jones and Greg D. Wells
Cancers 2021, 13(18), 4684; https://doi.org/10.3390/cancers13184684 - 18 Sep 2021
Cited by 4 | Viewed by 3068
Abstract
Stress is a ubiquitous experience that can be adaptive or maladaptive. Physiological stress regulation, or allostasis, can be disrupted at any point along the regulatory pathway resulting in adverse effects for the individual. Children with cancer exhibit significant changes to these pathways in [...] Read more.
Stress is a ubiquitous experience that can be adaptive or maladaptive. Physiological stress regulation, or allostasis, can be disrupted at any point along the regulatory pathway resulting in adverse effects for the individual. Children with cancer exhibit significant changes to these pathways in line with stress dysregulation and long-term effects similar to those observed in other early-life stress populations, which are thought to be, in part, a result of cytotoxic cancer treatments. Children with cancer may have disruption to several steps in the stress-regulatory pathway including cognitive-affective function, neurological disruption to stress regulatory brain regions, altered adrenal and endocrine function, and disrupted tissue integrity, as well as lower engagement in positive coping behaviours such as physical activity and pro-social habits. To date, there has been minimal study of stress reactivity patterns in childhood illness populations. Nor has the role of stress regulation in long-term health and function been elucidated. We conclude that consideration of stress regulation in childhood cancer may be crucial in understanding and treating the disease. Full article
(This article belongs to the Special Issue Pediatric Cancers)
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21 pages, 2521 KiB  
Systematic Review
A Systematic Review and Meta-Analysis of Malignant Rhabdoid and Small Cell Undifferentiated Liver Tumors: A Rational for a Uniform Classification
by Juri Fuchs, Anastasia Murtha-Lemekhova, Markus Kessler, Fabian Ruping, Patrick Günther, Alexander Fichtner, Dominik Sturm and Katrin Hoffmann
Cancers 2022, 14(2), 272; https://doi.org/10.3390/cancers14020272 - 06 Jan 2022
Cited by 6 | Viewed by 2016
Abstract
Background: Rhabdoid liver tumors in children are rare and have a devastating prognosis. Reliable diagnosis and targeted treatment approaches are urgently needed. Immunohistochemical and genetic studies suggest that tumors formerly classified as small cell undifferentiated hepatoblastoma (SCUD) belong to the entity of malignant [...] Read more.
Background: Rhabdoid liver tumors in children are rare and have a devastating prognosis. Reliable diagnosis and targeted treatment approaches are urgently needed. Immunohistochemical and genetic studies suggest that tumors formerly classified as small cell undifferentiated hepatoblastoma (SCUD) belong to the entity of malignant rhabdoid tumors of the liver (MRTL), in contrast to hepatoblastomas with focal small cell histology (F-SCHB). This may have relevant implications on therapeutic approaches. However, studies with larger cohorts investigating the clinical relevance of the histological and genetic similarities for patients are lacking. Purpose: To analyze possible similarities and differences in patient characteristics, tumor biology, response to treatment, and clinical course of patients with MRTL, SCUD and F-SCHB. Applied therapeutic regimens and prognostic factors are investigated. Methods: A systematic literature search of MEDLINE, Web of Science, and CENTRAL was performed for this PRISMA-compliant systematic review. All studies of patients with MRTL, SCUD and F-SCHB that provided individual patient data were included. Demographic, histological, and clinical characteristics of the three subgroups were compared. Overall survival (OS) was estimated with the Kaplan–Meier method and prognostic factors investigated in a multivariable Cox regression model. Protocol registered: PROSPERO 2021 CRD42021258760. Results: Fifty-six studies with a total of 118 patients were included. The two subgroups MRTL and SCUD did not differ significantly in baseline patient characteristics. However, heterogenous diagnostic and therapeutic algorithms were applied. Large histological and clinical overlap between SCUD and MRTL could be shown. Two-year OS was 22% for MRTL and 13% for SCUD, while it was significantly better in F-SCHD (86%). Chemotherapeutic regimens for hepatoblastoma proved to be ineffective for both SCUD and MRTL, but successful in F-SCHB. Soft tissue sarcoma chemotherapy was associated with significantly better survival for MRTL and SCUD, but was rarely applied in SCUD. Patients who did not undergo surgical tumor resection had a significantly higher risk of death. Conclusions: While F-SCHB is a subtype of HB, SCUD should be classified and treated as a type of MRTL. Surgical tumor resection in combination with intensive, multi-agent chemotherapy is the only chance for cure of these tumors. Targeted therapies are highly needed to improve prognosis. Currently, aggressive regimens including soft tissue sarcoma chemotherapy, extensive resection, radiotherapy or even liver transplantation are the only option for affected children. Full article
(This article belongs to the Special Issue Pediatric Cancers)
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2 pages, 173 KiB  
Correction
Correction: Welter et al. Characteristics of Nephroblastoma/Nephroblastomatosis in Children with a Clinically Reported Underlying Malformation or Cancer Predisposition Syndrome. Cancers 2021, 13, 5016
by Nils Welter, Angelo Wagner, Rhoikos Furtwängler, Patrick Melchior, Leo Kager, Christian Vokuhl, Jens-Peter Schenk, Clemens Magnus Meier, Stefan Siemer, Manfred Gessler and Norbert Graf
Cancers 2021, 13(22), 5743; https://doi.org/10.3390/cancers13225743 - 16 Nov 2021
Cited by 2 | Viewed by 1037
Abstract
In the original article [...] Full article
(This article belongs to the Special Issue Pediatric Cancers)
21 pages, 3102 KiB  
Systematic Review
The Role of Chemotherapy in Management of Inoperable, Metastatic and/or Recurrent Melanotic Neuroectodermal Tumor of Infancy—Own Experience and Systematic Review
by Małgorzata Styczewska, Małgorzata A. Krawczyk, Ines B. Brecht, Konrad Haug, Ewa Iżycka-Świeszewska, Jan Godziński, Anna Raciborska, Marek Ussowicz, Wojciech Kukwa, Natalia Cwalina, Emil Lundstrom and Ewa Bień
Cancers 2021, 13(15), 3872; https://doi.org/10.3390/cancers13153872 - 31 Jul 2021
Cited by 4 | Viewed by 3569
Abstract
Melanotic Neuroectodermal Tumor of Infancy (MNTI) is a very rare pediatric neoplasm of neural crest origin. In most cases, it develops in infants as a localized tumor of the maxilla, and surgery is usually curative. In less than 10% of patients with inoperable, [...] Read more.
Melanotic Neuroectodermal Tumor of Infancy (MNTI) is a very rare pediatric neoplasm of neural crest origin. In most cases, it develops in infants as a localized tumor of the maxilla, and surgery is usually curative. In less than 10% of patients with inoperable, metastatic or persistently recurring MNTI, chemotherapy (CHT) may be considered; however, its role is still unclear. The aim of our study was to assess the efficacy of CHT in children with large, inoperable, metastatic and/or recurrent MNTI. Four such infants, treated with CHT in Polish and German centers of pediatric oncology, were presented. Additionally, a systematic literature search of the PubMed/MEDLINE, Scopus and Web of Science databases was performed, yielding 38 similar cases within the last 42 years. Neoadjuvant CHT, based mainly on the protocols for neuroblastoma, was often effective, allowing for complete delayed surgery in most cases. However, the role of adjuvant CHT in preventing recurrences after incomplete resection of MNTI remains unclear. Disseminated inoperable MNTI was almost universally associated with poor response to CHT and unfavorable outcome. Further investigations to elaborate standards of management in patients with inoperable, metastatic or persistently recurring MNTIs are necessary to improve outcomes. Full article
(This article belongs to the Special Issue Pediatric Cancers)
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