Prognostic Factors for Pediatric Tumors

A special issue of Diagnostics (ISSN 2075-4418). This special issue belongs to the section "Pathology and Molecular Diagnostics".

Deadline for manuscript submissions: closed (30 September 2023) | Viewed by 15818

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Special Issue Editors

3rd Department of Pediatrics, Hippokration General Hospital, Aristotle University of Thessaloniki, 546 42 Thessaloniki, Greece
Interests: childhood cancer; survivorship; late effects; acute lymphoblastic leukemia; rare tumors
Special Issues, Collections and Topics in MDPI journals
2nd Department of Pediatrics, Aristotle University of Thessaloniki and AHEPA University Hospital, 54638 Thessaloniki, Greece
Interests: childhood cancer; survivorship; adolescents and young adults with cancer; acute lymphoblastic leukemia; Hodgkin lymphoma; thrombosis

Special Issue Information

Dear Colleagues,

At present, it is estimated that over 80% of children diagnosed with cancer will be cured. This estimate is encouraging and reflects the significant progress achieved over the recent decades, in both supportive care and the risk stratification of patients. Despite these significant advancements in the treatment of pediatric cancers, childhood cancer remains one of the leading causes of death in children and adolescents worldwide. Considerable research efforts have been focused on the biological characterization of the disease, in order to refine risk group stratification and facilitate targeted therapies.

Biology has historically played a pivotal role in the prognostic risk assessment of childhood leukemia. The genomic landscape of pediatric leukemia has been mapped and redefined following large-scale sequencing efforts. Pediatric solid tumors are also biologically and morphologically heterogenous, and the interplay between histologic examination and molecular interrogation has a pivotal role in the prognostication and direction of therapy.

The incorporation of molecularly targeted therapies offers real promise for less toxic and more effective therapy. The identification of novel diagnostic and prognostic markers is required to individualize therapy.

The present Special Issue is focused on prognostic markers in pediatric cancer. We would like to kindly invite you to contribute your original research or high-quality review articles in this endeavor.

Dr. Maria Kourti
Dr. Emmanouel Hatzipantelis
Guest Editors

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Keywords

  • childhood cancer
  • prognostic factors
  • acute leukemia
  • solid tumors

Published Papers (11 papers)

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Editorial

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4 pages, 198 KiB  
Editorial
Evolving Aspects of Prognostic Factors for Pediatric Cancer
by Maria Kourti and Emmanouel Hatzipantelis
Diagnostics 2023, 13(23), 3515; https://doi.org/10.3390/diagnostics13233515 - 23 Nov 2023
Viewed by 445
Abstract
Advances in risk-directed therapy based on prognostic factors that include clinical, biologic, and genetic features of cancer in children have yielded improved and prolonged responses [...] Full article
(This article belongs to the Special Issue Prognostic Factors for Pediatric Tumors)

Research

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14 pages, 787 KiB  
Article
Impact of Cancer Type and Treatment Protocol on Cardiac Function in Pediatric Oncology Patients: An Analysis Utilizing Speckle Tracking, Global Longitudinal Strain, and Myocardial Performance Index
by Andrada Mara Ardelean, Ioana Cristina Olariu, Raluca Isac, Akhila Nalla, Ruxandra Jurac, Cristiana Stolojanu, Mircea Murariu, Roxana Manuela Fericean, Laurentiu Braescu, Adelina Mavrea, Catalin Dumitru and Gabriela Doros
Diagnostics 2023, 13(17), 2830; https://doi.org/10.3390/diagnostics13172830 - 31 Aug 2023
Cited by 1 | Viewed by 819
Abstract
Pediatric hemato-oncology patients undergoing anthracycline therapy are at risk of cardiotoxicity, with disease type and treatment intensity potentially affecting cardiac function. Novel echocardiographic measures like speckle tracking echocardiography (STE), global longitudinal strain (GLS), and the myocardial performance index (MPI) may predict early changes [...] Read more.
Pediatric hemato-oncology patients undergoing anthracycline therapy are at risk of cardiotoxicity, with disease type and treatment intensity potentially affecting cardiac function. Novel echocardiographic measures like speckle tracking echocardiography (STE), global longitudinal strain (GLS), and the myocardial performance index (MPI) may predict early changes in cardiac function not detected by traditional methods. This study aimed to assess the impact of cancer type and treatment protocol on these parameters and their potential in predicting long-term cardiac complications. We conducted a single-center, retrospective cohort study of 99 pediatric oncology patients and 46 controls that were assessed at 3, 6, and 12 months. The median age was 10.7 ± 4.4 years for cases and 10.2 ± 3.6 years for controls. STE, GLS, and MPI were measured, and statistical analyses were performed to determine any significant correlations with cardiotoxicity. Significant variations were observed in traditional cardiac function measurements between the patient and control groups, with a lower average ejection fraction (EF) of 62.8 ± 5.7% in patients vs. 66.4 ± 6.1% in controls (p < 0.001), poorer GLS of −16.3 ± 5.1 in patients compared to −19.0 ± 5.4 in controls (p = 0.004), and higher MPI values of 0.37 ± 0.06 in patients compared to 0.55 ± 0.10 in controls, indicating worse overall cardiac function (p < 0.001). However, differences in cardiac function measurements by cancer histology or treatment protocol were not statistically significant. Regression analyses showed that the combination of GLS, SMOD, and MPI increased the odds of cardiac toxicity with an odds ratio of 7.30 (95% CI: 2.65–12.81, p < 0.001). The study underscores the predictive value of the combined GLS, SMOD, and MPI measurements in pediatric oncology patients undergoing anthracycline treatment for cardiotoxicity. Although variations across cancer types and treatment protocols were not significant, the study emphasizes the potential utility of these novel echocardiographic measures in early detection and long-term prediction of anthracycline-induced cardiotoxicity. Further studies in larger, multi-center cohorts are required for validation. Full article
(This article belongs to the Special Issue Prognostic Factors for Pediatric Tumors)
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16 pages, 2088 KiB  
Article
The Prognostic Effect of CDKN2A/2B Gene Deletions in Pediatric Acute Lymphoblastic Leukemia (ALL): Independent Prognostic Significance in BFM-Based Protocols
by Mirella Ampatzidou, Stefanos I. Papadhimitriou, Anna Paisiou, Georgios Paterakis, Marianna Tzanoudaki, Vassilios Papadakis, Lina Florentin and Sophia Polychronopoulou
Diagnostics 2023, 13(9), 1589; https://doi.org/10.3390/diagnostics13091589 - 28 Apr 2023
Cited by 1 | Viewed by 1335
Abstract
One of the most frequent genes affected in pediatric ALL is the CDKN2A/2B gene, acting as a secondary cooperating event and playing an important role in cell-cycle regulation and chemosensitivity. Despite its inclusion in combined CNA (copy-number alterations) classifiers, like the IKZF1plus entity [...] Read more.
One of the most frequent genes affected in pediatric ALL is the CDKN2A/2B gene, acting as a secondary cooperating event and playing an important role in cell-cycle regulation and chemosensitivity. Despite its inclusion in combined CNA (copy-number alterations) classifiers, like the IKZF1plus entity and the UKALL CNA profile, the prognostic impact of the individual gene deletions outside the context of a combined CNA evaluation remains controversial. Addressing the CDKN2A/2B deletions’ additive prognostic effect in current risk-stratification algorithms, we present a retrospective study of a Greek pediatric ALL cohort comprising 247 patients studied over a 24-year period (2000–2023). Herein, we provide insight regarding the correlation with disease features, MRD clearance, and independent prognostic significance for this ALL cohort treated with contemporary BFM-based treatment protocols. Within an extended follow-up time of 135 months, the presence of the CDKN2A/2B deletions (biallelic or monoallelic) was associated with inferior EFS rates (65.1% compared to 91.8% for the gene non-deleted subgroup, p < 0.001), with the relapse rate accounting for 22.2% and 5.9%, respectively (p < 0.001). The presence of the biallelic deletion was associated with the worst outcomes (EFS 57.2% vs. 89.6% in the case of any other status, monoallelic or non-deleted, p < 0.001). Survival differences were demonstrated for B-ALL cases (EFS 65.3% vs. 93.6% for the non-deleted B-ALL subgroup, p < 0.001), but the prognostic effect was not statistically significant within the T-ALL cohort (EFS 64.3 vs. 69.2, p = 0.947). The presence of the CDKN2A/2B deletions clearly correlated with inferior outcomes within all protocol-defined risk groups (standard risk (SR): EFS 66.7% vs. 100%, p < 0.001, intermediate risk (IR): EFS 77.1% vs. 97.9%, p < 0.001, high risk (HR): EFS 42.1% vs. 70.5% p < 0.001 for deleted vs non-deleted cases in each patient risk group); additionally, in this study, the presence of the deletion differentiated prognosis within both MRD-positive and -negative subgroups on days 15 and 33 of induction. In multivariate analysis, the presence of the CDKN2A/2B deletions was the most important prognostic factor for relapse and overall survival, yielding a hazard ratio of 5.2 (95% confidence interval: 2.59–10.41, p < 0.001) and 5.96 (95% confidence interval: 2.97–11.95, p < 0.001), respectively, designating the alteration’s independent prognostic significance in the context of modern risk stratification. The results of our study demonstrate that the presence of the CDKN2A/2B deletions can further stratify all existing risk groups, identifying patient subgroups with different outcomes. The above biallelic deletions could be incorporated into future risk-stratification algorithms, refining MRD-based stratification. In the era of targeted therapies, future prospective controlled clinical trials will further explore the possible use of cyclin-dependent kinase inhibitors (CDKIs) in CDKN2A/2B-affected ALL pediatric subgroups. Full article
(This article belongs to the Special Issue Prognostic Factors for Pediatric Tumors)
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Review

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18 pages, 435 KiB  
Review
Proteomics in Childhood Acute Lymphoblastic Leukemia: Challenges and Opportunities
by Maria Kourti, Michalis Aivaliotis and Emmanouel Hatzipantelis
Diagnostics 2023, 13(17), 2748; https://doi.org/10.3390/diagnostics13172748 - 24 Aug 2023
Cited by 1 | Viewed by 1201
Abstract
Acute lymphoblastic leukemia (ALL) is the most common cancer in children and one of the success stories in cancer therapeutics. Risk-directed therapy based on clinical, biologic and genetic features has played a significant role in this accomplishment. Despite the observed improvement in survival [...] Read more.
Acute lymphoblastic leukemia (ALL) is the most common cancer in children and one of the success stories in cancer therapeutics. Risk-directed therapy based on clinical, biologic and genetic features has played a significant role in this accomplishment. Despite the observed improvement in survival rates, leukemia remains one of the leading causes of cancer-related deaths. Implementation of next-generation genomic and transcriptomic sequencing tools has illustrated the genomic landscape of ALL. However, the underlying dynamic changes at protein level still remain a challenge. Proteomics is a cutting-edge technology aimed at deciphering the mechanisms, pathways, and the degree to which the proteome impacts leukemia subtypes. Advances in mass spectrometry enable high-throughput collection of global proteomic profiles, representing an opportunity to unveil new biological markers and druggable targets. The purpose of this narrative review article is to provide a comprehensive overview of studies that have utilized applications of proteomics in an attempt to gain insight into the pathogenesis and identification of biomarkers in childhood ALL. Full article
(This article belongs to the Special Issue Prognostic Factors for Pediatric Tumors)
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17 pages, 345 KiB  
Review
Clinical, Histological, and Molecular Prognostic Factors in Childhood Medulloblastoma: Where Do We Stand?
by Charikleia Ntenti, Konstantinos Lallas and Georgios Papazisis
Diagnostics 2023, 13(11), 1915; https://doi.org/10.3390/diagnostics13111915 - 30 May 2023
Cited by 1 | Viewed by 1186
Abstract
Medulloblastomas, highly aggressive neoplasms of the central nervous system (CNS) that present significant heterogeneity in clinical presentation, disease course, and treatment outcomes, are common in childhood. Moreover, patients who survive may be diagnosed with subsequent malignancies during their life or could develop treatment-related [...] Read more.
Medulloblastomas, highly aggressive neoplasms of the central nervous system (CNS) that present significant heterogeneity in clinical presentation, disease course, and treatment outcomes, are common in childhood. Moreover, patients who survive may be diagnosed with subsequent malignancies during their life or could develop treatment-related medical conditions. Genetic and transcriptomic studies have classified MBs into four subgroups: wingless type (WNT), Sonic Hedgehog (SHH), Group 3, and Group 4, with distinct histological and molecular profiles. However, recent molecular findings resulted in the WHO updating their guidelines and stratifying medulloblastomas into further molecular subgroups, changing the clinical stratification and treatment management. In this review, we discuss most of the histological, clinical, and molecular prognostic factors, as well the feasibility of their application, for better characterization, prognostication, and treatment of medulloblastomas. Full article
(This article belongs to the Special Issue Prognostic Factors for Pediatric Tumors)
27 pages, 2704 KiB  
Review
Prognostic Factors for Cardiotoxicity among Children with Cancer: Definition, Causes, and Diagnosis with Omics Technologies
by Kondylia Antoniadi, Nikolaos Thomaidis, Petros Nihoyannopoulos, Konstantinos Toutouzas, Evangelos Gikas, Charikleia Kelaidi and Sophia Polychronopoulou
Diagnostics 2023, 13(11), 1864; https://doi.org/10.3390/diagnostics13111864 - 26 May 2023
Cited by 1 | Viewed by 1184
Abstract
Improvements in the treatment of childhood cancer have considerably enhanced survival rates over the last decades to over 80% as of today. However, this great achievement has been accompanied by the occurrence of several early and long-term treatment-related complications major of which is [...] Read more.
Improvements in the treatment of childhood cancer have considerably enhanced survival rates over the last decades to over 80% as of today. However, this great achievement has been accompanied by the occurrence of several early and long-term treatment-related complications major of which is cardiotoxicity. This article reviews the contemporary definition of cardiotoxicity, older and newer chemotherapeutic agents that are mainly involved in cardiotoxicity, routine process diagnoses, and methods using omics technology for early and preventive diagnosis. Chemotherapeutic agents and radiation therapies have been implicated as a cause of cardiotoxicity. In response, the area of cardio-oncology has developed into a crucial element of oncologic patient care, committed to the early diagnosis and treatment of adverse cardiac events. However, routine diagnosis and the monitoring of cardiotoxicity rely on electrocardiography and echocardiography. For the early detection of cardiotoxicity, in recent years, major studies have been conducted using biomarkers such as troponin, N-terminal pro b-natriuretic peptide, etc. Despite the refinements in diagnostics, severe limitations still exist due to the increase in the above-mentioned biomarkers only after significant cardiac damage has occurred. Lately, the research has expanded by introducing new technologies and finding new markers using the omics approach. These new markers could be used not only for early detection but also for the early prevention of cardiotoxicity. Omics science, which includes genomics, transcriptomics, proteomics, and metabolomics, offers new opportunities for biomarker discovery in cardiotoxicity and may provide an understanding of the mechanisms of cardiotoxicity beyond traditional technologies. Full article
(This article belongs to the Special Issue Prognostic Factors for Pediatric Tumors)
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20 pages, 3247 KiB  
Review
Predictive Factors for Pediatric Craniopharyngioma Recurrence: An Extensive Narrative Review
by Anastasios Serbis, Vasiliki Rengina Tsinopoulou, Anastasia Papadopoulou, Savvas Kolanis, Eleni I. Sakellari, Kosmas Margaritis, Eleni Litou, Stergianna Ntouma, Styliani Giza, Eleni P. Kotanidou and Assimina Galli-Tsinopoulou
Diagnostics 2023, 13(9), 1588; https://doi.org/10.3390/diagnostics13091588 - 28 Apr 2023
Cited by 2 | Viewed by 1289
Abstract
Despite being classified as benign tumors, craniopharyngiomas (CPs) are associated with significant morbidity and mortality due to their location, growth pattern, and tendency to recur. Two types can be identified depending on age distribution, morphology, and growth pattern, adamantinomatous and papillary. The adamantinomatous [...] Read more.
Despite being classified as benign tumors, craniopharyngiomas (CPs) are associated with significant morbidity and mortality due to their location, growth pattern, and tendency to recur. Two types can be identified depending on age distribution, morphology, and growth pattern, adamantinomatous and papillary. The adamantinomatous CP is one of the most frequently encountered central nervous system tumors in childhood. Our aim was to review the relevant literature to identify clinical, morphological, and immunohistochemical prognostic factors that have been implicated in childhood-onset CP recurrence. Lack of radical surgical removal of the primary tumor by an experienced neurosurgical team and radiotherapy after a subtotal excision has been proven to significantly increase the recurrence rate of CP. Other risk factors that have been consistently recognized in the literature include younger age at diagnosis (especially <5 years), larger tumor size at presentation, cystic appearance, difficult tumor location, and tight adherence to surrounding structures, as well as the histological presence of whorl-like arrays. In addition, several other risk factors have been studied, albeit with conflicting results, especially in the pediatric population. Identifying risk factors for CP recurrence is of utmost importance for the successful management of these patients in order to ultimately ensure the best prognosis. Full article
(This article belongs to the Special Issue Prognostic Factors for Pediatric Tumors)
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23 pages, 662 KiB  
Review
Therapeutic Management and Prognostic Factors for Ovarian Malignant Tumours in Adolescents: A Comprehensive Review of Current Guidelines
by Chrysoula Margioula-Siarkou, Stamatios Petousis, Georgia Margioula-Siarkou, George Mavromatidis, Fotios Chatzinikolaou, Emmanouel Hatzipantelis, Frédéric Guyon and Konstantinos Dinas
Diagnostics 2023, 13(6), 1080; https://doi.org/10.3390/diagnostics13061080 - 13 Mar 2023
Cited by 5 | Viewed by 1730
Abstract
Background: Ovarian malignant tumours are rarely diagnosed in adolescents but may have a significant impact on their survival, future fertility and quality of life. The management of such cases is rather complex and requires expertise and careful planning according to scarce existing evidence [...] Read more.
Background: Ovarian malignant tumours are rarely diagnosed in adolescents but may have a significant impact on their survival, future fertility and quality of life. The management of such cases is rather complex and requires expertise and careful planning according to scarce existing evidence and recommendations. Objective: The aim of this study was to review and compare recommendations from published guidelines regarding the diagnosis, prognosis and treatment of malignant ovarian tumours in adolescents. Evidence acquisition: A comparative descriptive/narrative review of guidelines issued by L’Observatoire des Tumeurs Malignes Rares Gynécologiques, the British Society for Paediatric & Adolescent Gynaecology, the European Society for Medical Oncology, the European Society of Gynecological Oncology-European Society for Paediatric Oncology and the European Cooperative Study Group for Pediatric Rare Tumors was conducted. Results: All guidelines recommend a thorough diagnostic work-up, consisting of both imaging tests and serum tumour marker measurement, as well as the use of immunohistochemical methods to confirm the diagnosis and complete surgical staging prior to constructing the treatment plan. There is a lack of recommendations regarding the assessment of prognostic factors, with only one guideline providing detailed information. Treatment strategies, as suggested by the majority of guidelines and with only a few discrepancies between them, should include both surgery and adjuvant therapies, mainly chemotherapy, with great emphasis on fertility preservation when it is considered oncologically safe and on the significance of regular and long-term follow-up. Conclusions: There is a significant degree of agreement among recommendations of existing guidelines. The reported differences, although limited, highlight the need for the adoption of an international consensus in order to further improve the management of adolescent ovarian cancer. Full article
(This article belongs to the Special Issue Prognostic Factors for Pediatric Tumors)
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15 pages, 298 KiB  
Review
Sarcoma Botryoides: Optimal Therapeutic Management and Prognosis of an Unfavorable Malignant Neoplasm of Female Children
by Chrysoula Margioula-Siarkou, Stamatios Petousis, Aristarchos Almperis, Georgia Margioula-Siarkou, Antonio Simone Laganà, Maria Kourti, Alexios Papanikolaou and Konstantinos Dinas
Diagnostics 2023, 13(5), 924; https://doi.org/10.3390/diagnostics13050924 - 01 Mar 2023
Cited by 4 | Viewed by 2106
Abstract
Embryonal rhabdomyosarcoma (ERMS) is a rare malignancy and occurs primarily in the first two decades of life. Botryoid rhabdomyosarcoma is an aggressive subtype of ERMS that often manifests in the genital tract of female infants and children. Due to its rarity, the optimal [...] Read more.
Embryonal rhabdomyosarcoma (ERMS) is a rare malignancy and occurs primarily in the first two decades of life. Botryoid rhabdomyosarcoma is an aggressive subtype of ERMS that often manifests in the genital tract of female infants and children. Due to its rarity, the optimal treatment approach has been a matter of debate. We conducted a search in the PubMed database and supplemented it with a manual search to retrieve additional papers eligible for inclusion. We retrieved 13 case reports and case series, from which we summarized that the current trend is to approach each patient with a personalized treatment plan. This consists of a combination of local debulking surgery and adjuvant or neoadjuvant chemotherapy (NACT). Effort is made in every approach to avoid radiation for the sake of preserving fertility. Radical surgeries and radiation still have a role to play in extensive disease and in cases of relapse. Despite the rarity and aggressiveness of this tumor, disease-free survival and overall prognosis is excellent, especially when it is diagnosed early, compared with other subtypes of rhabdomyosarcoma (RMS). We conclude that the practice of a multidisciplinary approach is appropriate, with favorable outcomes; however, larger-scale studies need to be organized to have a definite consensus on optimal management. Full article
(This article belongs to the Special Issue Prognostic Factors for Pediatric Tumors)
13 pages, 618 KiB  
Review
Nutritional Status at Diagnosis as Predictor of Survival from Childhood Cancer: A Review of the Literature
by Maria A. Karalexi, Georgios Markozannes, Christos F. Tagkas, Andreas Katsimpris, Xanthippi Tseretopoulou, Konstantinos K. Tsilidis, Logan G. Spector, Joachim Schüz, Tania Siahanidou, Eleni Th. Petridou and Evangelia E. Ntzani
Diagnostics 2022, 12(10), 2357; https://doi.org/10.3390/diagnostics12102357 - 28 Sep 2022
Cited by 3 | Viewed by 1989
Abstract
Few studies so far have examined the impact of nutritional status on the survival of children with cancer, with the majority of them focusing on hematological malignancies. We summarized published evidence reporting the association of nutritional status at diagnosis with overall survival (OS), [...] Read more.
Few studies so far have examined the impact of nutritional status on the survival of children with cancer, with the majority of them focusing on hematological malignancies. We summarized published evidence reporting the association of nutritional status at diagnosis with overall survival (OS), event-free survival (EFS), relapse, and treatment-related toxicity (TRT) in children with cancer. Published studies on children with leukemia, lymphoma, and other solid tumors have shown that both under-nourished and over-nourished children at cancer diagnosis had worse OS and EFS. Particularly, the risk of death and relapse increased by 30–50% among children with leukemia with increased body mass index at diagnosis. Likewise, the risk of TRT was higher among malnourished children with osteosarcoma and Ewing sarcoma. Nutritional status seems to play a crucial role in clinical outcomes of children with cancer, thus providing a significant modifiable prognostic tool in childhood cancer management. Future studies with adequate power and longitudinal design are needed to further evaluate the association of nutritional status with childhood cancer outcomes using a more standardized definition to measure nutritional status in this population. The use of new technologies is expected to shed further light on this understudied area and give room to person-targeted intervention strategies. Full article
(This article belongs to the Special Issue Prognostic Factors for Pediatric Tumors)
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Other

18 pages, 8998 KiB  
Systematic Review
The Prognostic Significance of BRAF Gene Analysis in Children and Adolescents with Papillary Thyroid Carcinoma: A Systematic Review and Meta-Analysis
by Eleni P Kotanidou, Styliani Giza, Vasiliki Rengina Tsinopoulou, Kosmas Margaritis, Anastasia Papadopoulou, Eleni Sakellari, Savvas Kolanis, Eleni Litou, Anastasios Serbis and Assimina Galli-Tsinopoulou
Diagnostics 2023, 13(6), 1187; https://doi.org/10.3390/diagnostics13061187 - 21 Mar 2023
Cited by 4 | Viewed by 1650
Abstract
Thyroid cancer represents the prominent endocrine cancer in children. Papillary thyroid cancer (PTC) constitutes its most frequent (>90%) pediatric histological type. Mutations energizing the mitogen-activated-protein kinase (MAPK) pathway are definitely related to PTC. Its most common genetic alteration is in proto-oncogene B-Raf (BRAF). [...] Read more.
Thyroid cancer represents the prominent endocrine cancer in children. Papillary thyroid cancer (PTC) constitutes its most frequent (>90%) pediatric histological type. Mutations energizing the mitogen-activated-protein kinase (MAPK) pathway are definitely related to PTC. Its most common genetic alteration is in proto-oncogene B-Raf (BRAF). Mutated BRAF is proposed as a prognostic tool in adult PTC. We conducted a systematic review and meta-analysis evaluating the association of mutated BRAF gene and prognostic clinicopathological characteristics of PTC in children/adolescents. Systematic search for relevant studies included PubMed, MEDLINE, Scopus, clinicaltrials.gov and Cochrane Library. Pooled estimates of odds ratios for categorical data and mean difference for continuous outcomes were calculated using random/fixed-effect meta-analytic models. BRAFV600E mutation presents a pooled pediatric/adolescent prevalence of 33.12%. Distant metastasis is significantly associated with mutated BRAF gene (OR = 0.32, 95% CI = 0.16–0.61, p = 0.001). Tumor size (MD = −0.24, 95% CI = −0.62–0.135, p = 0.21), multifocality (OR = 1.13, 95% CI = 0.65–2.34, p = 0.74), vascular invasion (OR = 1.17, 95% CI = 0.67–2.05, p = 0.57), lymph node metastasis (OR = 0.92, 95% CI = 0.63–1.33, p = 0.66), extra-thyroid extension (OR = 0.78, 95% CI = 0.53–1.13, p = 0.19) and tumor recurrence (OR = 1.66, 95% CI = 0.68–4.21, p = 0.376) presented no association or risk with BRAF mutation among pediatric/adolescent PTC. Mutated BRAF gene in children and adolescents is less common than in adults. Mutation in BRAF relates significantly to distant metastasis among children/adolescents with PTC. Full article
(This article belongs to the Special Issue Prognostic Factors for Pediatric Tumors)
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