Search Results (245)

Childhood acute lymphoblastic leukemia (ALL) is the most common pediatric cancer, and while chemotherapy has significantly improved survival rates, it can also lead to long-term side effects, including immune system dysfunction. This study aimed to investigate in detail, using flow cytometry, the T-cell subpopulations in the peripheral blood of children who have completed ALL treatment and compare them to a group of healthy children. The study group consisted of 20 patients, aged 5 to 18 years, with blood samples collected at least one year after treatment completion. Of the 52 T-cell subpopulations analyzed, 16 showed statistically significant differences. Children after ALL treatment had lower absolute values of TCRγδ+ and higher values of double-positive CD4+CD8+ and CD8+ T cells. They also had higher absolute numbers of memory T cells, including total CD45RO+ T cells, and the CD45RO+CD8+ and CD45RO+CD27+ subpopulations. Furthermore, post treatment patients showed higher absolute values of activated T cells (HLA-DR+, HLA-DR+CD8+, HLA-DR+CD57+, and CD25+CD8+), as well as CD57+ and CCR7+ T cells. The absolute leukocyte and granulocyte counts were lower in the study group, while the total lymphocyte count was significantly higher compared to the control group. The findings indicate persistent changes in T-cell subpopulations after ALL treatment, suggesting ongoing immune system rebuilding and chronic antigenic stimulation, possibly due to viral reactivation or chemotherapy-related tissue damage. The increased number of TCRγδ+ cells, which are responsible for eliminating cancer cells, may be a positive aspect of this rebuilding. Full article

Background/Objectives: Treatment of childhood ependymoma evolved from 1970 to 1999 by reducing radiation volumes and incorporating chemotherapy. The impact of these changes on long-term health outcomes remains unknown. In this report, we evaluated temporal changes in all-cause and cause-specific late mortality, chronic health conditions (CHCs), and subsequent neoplasms (SNs) in the Childhood Cancer Survivor Study (CCSS) cohort of adult survivors of pediatric ependymoma, diagnosed between 1970 and 1999. Methods: A total of 404 five-year survivors of ependymoma (47.5% female, 80.7% non-Hispanic White, median 6 (range 0–20) years at diagnosis, 22 (5–49) years from diagnosis) diagnosed between 1970 and 1999 and enrolled in the Childhood Cancer Survivor Study were evaluated for late (>5 years from diagnosis) mortality, SNs, and CHCs. Outcomes were analyzed by diagnosis decade, radiotherapy, and chemotherapy exposure. Gray’s test compared cumulative incidences. Multivariable piecewise exponential models estimated relative risks (RRs). Results: Whole-brain radiation exposure decreased over time (42.9% (1970s) to 2.7% (1990s)), while focal radiation (21.4% to 68.9%), and chemotherapy (29.5% to 50.2%) use increased. Fifteen-year all-cause late mortality (incidence, 95% CI) remained similar across decades: 1970s (9.3%, 3.4–18.8%), 1980s (14.7%, 9.4–21.2%), 1990s (10.3%, 6.7–14.9%). All-cause late mortality was higher after treatment with whole-brain radiation (22.5%, 11.2–36.5%) compared to focal radiation (11.4%, 7.5–16.1%) or no brain radiation (3.5%, 0.9–9.1%) (p < 0.001), and with chemotherapy (14.4%, 9.6–20.0%) versus without (6.8%, 3.8–11.0%) (p = 0.004). Compared to no brain radiation, the RR (95% CI) of grade 3–4 CHCs increased among survivors treated with focal (2.6, 1.3–5.4) and whole-brain radiation (3.5, 1.5–8.1), while chemotherapy was not associated with CHCs or SNs. Conclusions: Despite reduced radiation volumes and increased use of chemotherapy, late mortality and morbidity among pediatric ependymoma survivors remained largely unchanged across treatment decades. Full article

Background: Pediatric oncological diagnoses and treatments pose complex biopsychosocial challenges for both patients and their families. These experiences can significantly disrupt daily life, evoke intense emotional responses, and raise concerns about the future, often leading to long-term psychological implications. Objective: This study aimed to assess the emotional functioning of children undergoing cancer treatment and to explore the lasting psychological effects reported by young adult survivors of pediatric cancer. Methods: A mixed-methods approach was employed. In total, 52 minors and their caregivers were recruited from two pediatric oncology units in Italy (Turin and Bari), while 18 young adults diagnosed during childhood were recruited from clinical and community settings in Ancona and Bari. Standardized instruments were used to evaluate emotional symptoms and broader psychological functioning in the pediatric sample, while self-report measures assessed psychological well-being and quality of life in the young adult group. To complement these data, semi-structured interviews were conducted with the young adult survivors to investigate the long-term psychosocial and psychological impacts of pediatric cancer. Results: The quantitative results indicate generally low levels of psychological distress in both groups. However, the qualitative findings reveal the complexity of post-cancer identity, highlighting experiences of resilience, emotional ambivalence, and redefinition of self. Conclusions: These results underscore the importance of addressing the psychological well-being of pediatric oncology patients and young adult survivors beyond the medical treatment phase, with a focus on long-term psychosocial support and individualized care. Full article

Cancer survivors (CS) constitute an expanding population with underrecognized cardiometabolic risk. Despite substantial improvements in five-year survival rates, both childhood and adult survivors remain at high risk for premature morbidity and mortality. These risks are particularly pronounced following exposure to anthracyclines and/or chest radiotherapy, typically in a dose-dependent manner. In Chile, the establishment of the National Pediatric Antineoplastic Drug Program (PINDA) in 1998 marked a milestone in improving equitable access to high-quality pediatric oncology care through evidence-based treatment protocols across the public health system; the adult counterpart (PANDA) has developed diagnostic, treatment, and monitoring protocols for hematological neoplasms. Few prospective cohort or mechanistic studies have clarified risk stratification or surveillance strategies in survivor populations. The regulated, short-term activation of inflammation and innate immunity can be an adaptive and protective response to tissue injury, whereas persistent low-grade inflammation may trigger neutrophil extracellular traps formation (NETosis) and other maladaptive pathways that accelerate endothelial injury, thrombosis, and adverse cardiovascular remodeling. NETosis represents a putative immunomodulatory target for therapeutic immunomodulation in heart failure and maladaptive left ventricular remodeling in preclinical models. Concurrently, skeletal muscle-derived and hormonal mediators known as exerkines—together with increased NET activity—may modulate the pathophysiology of chronic cardiometabolic disease and contribute to cancer progression, particularly in the context of obesity, diabetes, and insulin resistance. Structured exercise is a promising non-pharmacological intervention that modulates inflammatory and metabolic pathways and may thereby help prevent non-communicable diseases, including cancer. We synthesize basic and clinical evidence to (1) define how cancer therapies promote low-grade inflammation and NETosis; (2) describe how exerkines and structured exercise influence cardiometabolic biology; and (3) evaluate exercise as a mechanistic and clinically pragmatic strategy to reduce long-term CVD risk in pediatric and adult CS. Full article

Background/Objectives: Full-spine radiography is frequently performed from childhood to adulthood, raising concerns about radiation-induced breast cancer risk. To assess such probabilistic risks as cancer, accurate estimation of equivalent and effective organ doses is essential. The purpose of this study is to investigate X-ray imaging conditions for radiation reduction based on breast organ dose and to evaluate the accuracy of simulation software for dose calculation. Methods: Breast organ doses from full-spine radiography were calculated using the Monte Carlo-based dose calculation software PCXMC. Breast organ doses were estimated under various technical conditions of full-spine radiography (tube voltage, distance, grid presence, and beam projection). Dose reduction methods were explored, and variations in dose and error due to phantom characteristics and photon history number were evaluated. Results: Among the X-ray conditions, the greatest radiation reduction effect was achieved by changing the imaging direction. Changing from the anteroposterior to posteroanterior direction reduced doses by approximately 76.7% to 89.1% (127.8–326.7 μGy) in children and 80.4% to 91.1% (411.3–911.1 μGy) in adults. In addition, the study highlighted how phantom characteristics and the number of photon histories influence estimated doses and calculation error, with approximately 2 × 10⁶ photon histories recommended to achieve a standard error ≤ 2%. Conclusions: Modifying radiographic conditions is effective for reducing breast radiation exposure in patients with scoliosis. Furthermore, to ensure the accuracy of dose calculation software, the number of photon histories must be adjusted under certain conditions and used while verifying the standard error. This study demonstrates how technical modifications, projection selection, and phantom characteristics influence breast radiation exposure, thereby supporting the need for patient-tailored imaging strategies that minimize radiation risk while maintaining diagnostic validity. The findings may be useful in informing radiographic protocols and the development of safer imaging guidelines for both pediatric and adult patients undergoing spinal examinations. Full article

Background: Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy, yet diagnosis still relies primarily on invasive bone-marrow procedures and advanced laboratory assays. Non-invasive, rapid, and cost-effective tools remain an unmet need. Fourier-transform infrared (FTIR) spectroscopy has shown promise for detecting cancer-associated biochemical changes in biofluids and cells. Methods: Serum from pediatric ALL patients and controls (n = 103; ALL = 45, controls = 58: healthy = 14, hematology controls = 44 with anemia, thrombocytopenia, leukopenia, and pancytopenia) was analyzed using FTIR. Spectra (800–1800, 2800–3500 cm⁻¹) were preprocessed with baseline correction, derivative filtering, and normalization. Group differences were assessed statistically, and logistic regression with stratified 10-fold cross-validation was applied; Receiver operating characteristic (ROC)\precision–recall (PR) analyses were based on out-of-fold predictions. Results: Distinct spectral alterations were observed between ALL and controls. Leukemia samples showed higher amide I (~1640 cm⁻¹) and amide II (~1545 cm⁻¹) absorbance, lower lipid-related bands (~1450, ~2920 cm⁻¹), and increased nucleic-acid–associated signals (~1080 cm⁻¹). Differences were significant (q < 0.05) with moderate effect sizes. Logistic regression achieved area under the curve (AUC) ≈ 0.80 with sensitivity ~0.73–0.84 across practical decision thresholds (0.50 → 0.30) and higher recall attainable at the expense of specificity. Principal component analysis (PCA)\hierarchical cluster analysis (HCA) indicated partial but consistent group separation, aligning with supervised performance. Conclusions: Serum FTIR spectroscopy shows promise for distinguishing pediatric ALL from controls by reflecting disease-related metabolic changes. The technique is rapid, label-free, and requires only small serum volumes. Our findings represent proof-of-concept, and validation in larger, multi-center studies is needed before clinical implementation can be considered. Full article

Acute lymphoblastic leukemia (ALL) remains the most frequent pediatric malignancy, accounting for approximately 34% of all pediatric cancers, with remarkable improvements in survival (approximately 85%) due to advances in chemotherapy, radiotherapy, and supportive care. However, as survival rates have increased, new challenges have emerged—particularly the growing prevalence of obesity and metabolic syndrome among survivors. This review compiles evidence from the past decade on the relationship between leukemia treatment, obesity, and metabolic risk. The findings indicate that cranial radiotherapy, corticosteroid use, and younger age at diagnosis are key risk factors for excessive weight gain and long-term metabolic disturbances. Genetic factors such as FTO, MC4R, and LEPR polymorphisms may further influence susceptibility to obesity. Nutritional analyses highlight poor diet quality, insufficient micronutrient intake, and high-fat, energy-dense dietary patterns in survivors. Beyond endocrine dysfunction, obesity and metabolic syndrome are associated with elevated cardiovascular morbidity and reduced quality of life. Personalized medicine approaches—integrating genomics, metabolomics, and lifestyle data—hold promise for targeted prevention and intervention strategies. Early detection, continuous metabolic monitoring, and health education remain essential components in the long-term management of childhood leukemia survivors. In this review, we analyzed the dietary patterns of children and long-term leukemia survivors explaining why higher rates of obesity and comorbidities appear during or after treatments, and discussed interventions to prevent these conditions. Full article

Childhood cancer is rare, with about 1 in 260 children developing cancer before age 20. However, it remains a leading cause of death for children and adolescents worldwide. The 5-year survival rate for childhood cancer in high-income countries exceeds 80%, but globally, the average survival rate is around 37%, highlighting significant disparities across the globe. Despite the life-saving impact of current treatment regimens, long-term side effects and risks are always concerns. Therefore, there is a continuing urgent need for novel therapies to overcome the limitations of existing approaches and improve patient outcomes. Targeted drug therapies that interfere with cancer-causing genes play a vital role in cancer treatment by specifically targeting cancer cells. TFs are primary drivers of gene expression that are critical in various pediatric cancers. Chromosomal rearrangements, involving changes in chromosome structure such as deletions, duplications, inversions, and translocations, can significantly alter TF activity and downstream gene expression. Dysregulation of TFs disrupts gene expression networks and has been strongly linked to the development and progression of many pediatric cancers, making them promising therapeutic targets. Several approaches targeting TFs, including small-molecule inhibitors designed to block TF-DNA binding, TF-cofactor interactions, or their epigenetic regulation, as well as RNA interference, have been developed. More recently, approaches like PROTACs (Proteolysis-Targeting Chimeras) and molecular glue degraders offer new therapeutic possibilities in pediatric cancers. These innovations represent a paradigm shift in pediatric oncology, offering hope for more targeted, less toxic treatment options. This review discusses the critical role of TFs in childhood cancers and emphasizes the need for evolving therapeutic strategies aimed at targeting these key regulators to improve outcomes for young patients. Full article

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. In Mexico, its higher incidence and lower survival suggest a role for epigenetic factors like DNA methylation (DNAme). We conducted an epigenome-wide association study (EWAS) to define the methylation landscape and identify the profiles associated with ALL and relapse. Bone marrow or peripheral blood samples from pediatric ALL patients at diagnosis and controls without ALL were analyzed using an Infinium MethylationEPIC v2.0 array. Differential methylation was assessed using the ChAMP package. We identified a significant hypermethylated profile in ALL patients compared to controls. Probes in MAD1L1 and RPTOR contained the most differentially methylated CpG sites. Key affected pathways included proliferation, neurotransmission, and neuronal signaling. Survival analysis revealed that hypomethylation of four specific CpGs—cg01052776 (RNH1), cg20747787, cg05001671, and cg01767116 (FBXL22)—was significantly associated with an increased risk of relapse, highlighting their potential as prognostic biomarkers. This study underscores the importance of epigenetic mechanisms in pediatric ALL. Full article

Background: Recent advances in childhood cancer treatment and increased survival rates have led to a growing number of adolescents and young adults (AYAs) who are survivors of childhood cancer (CCSs). This study aimed to examine health status, health-related quality of life (HRQoL), and social outcomes in AYA CCSs. Methods: Sixty-two AYAs who were CCSs (treated within the same tertiary Pediatric Hematology–Oncology Department in Crete, Greece) were enrolled in the study. Self-reported HRQoL was assessed using the Short-Form Health Survey (SF-36). Sixty-five never-ill peers constituted the control group. Results: CCSs reach adolescence and young adulthood without significant deviations in HRQoL from their healthy peers. The presence and severity of late effects were significantly correlated with lower scores in physical health. The cancer type seems to play a pivotal role: Langerhans cell histiocytosis survivors displayed significantly lower scores in mental health, and brain tumor survivors scored substantially lower scores in physical functioning. Acute lymphoblastic leukemia survivors reported the highest scores in mental health. Age at diagnosis of neoplasia was negatively correlated with physical functioning. No significant sex differences were identified. Adherence to multiple healthy lifestyle behaviors (regular exercise, abstaining from alcohol consumption and smoking, and using sun protection) and active employment were correlated with significantly higher scores in mental health. Conclusions: Appropriate therapy and regular follow-up after treatment have led to improved clinical and social outcomes, as assessed by CCSs. More efforts are needed to increase awareness of avoiding harmful behaviors that raise the risk of late effects in this specific group. Full article

Neuroblastoma is a devastating pediatric solid tumor that, despite significant recent advances, still accounts for nearly 15% of all childhood cancer deaths. Patients are risk stratified based on a number of features, including amplification of the MYCN oncogene, yet targeting MYCN itself has been unsuccessful to date. The complex interplay between this oncogene and its many metabolic targets has proven challenging and is only beginning to be understood in the context of pediatric tumors. It is increasingly recognized, however, that MYCN-driven metabolic rewiring and concomitant increases in biosynthetic precursors has the potential to drive many aspects of tumor development. Furthermore, emerging research suggests that improving overall therapeutic outcomes for neuroblastoma patients may well require individual metabolic profiling, allowing personalized simultaneous targeting of multiple metabolic nodes. In this review, we outline clinically relevant research involving MYCN-driven metabolic derangements, including increased glucose uptake, polyamine synthesis, glycosylation, and others, and attempt to summarize the influence of MYCN on important metabolic genes and druggable protein targets. We spotlight emerging research in glycosylation and its modulation as an often overlooked but increasingly promising therapeutic area. It is our hope that this document will provide utility for both clinicians and scientists seeking to understand how the MYCN oncogene and metabolism are critically intertwined. Full article

Background/Objectives: Neuroblastoma (NB) is an aggressive pediatric malignancy that accounts for nearly 15% of all childhood cancer-related deaths, with high-risk cases showing a poor 20% prognosis and limited response to current therapies. Survivin, encoded by the BIRC5 gene, is an anti-apoptotic protein frequently overexpressed in NB and linked to treatment resistance and unfavorable clinical outcomes. Methods and Results: An analysis of 1235 NB patient datasets revealed a significant association between elevated BIRC5 expression and reduced overall and event-free survival, highlighting survivin as an important therapeutic target in NB. To explore this strategy, we evaluated the efficacy of YM-155, a small-molecule survivin inhibitor, across multiple NB cell lines. YM-155 displayed potent cytotoxic activity in six NB cell lines with IC₅₀ values ranging from 8 to 212 nM and significantly inhibited colony formation and 3D spheroid growth in a dose-dependent manner. Mechanistic analyses revealed that YM-155 downregulated survivin at both mRNA and protein levels, induced apoptosis by about 2–7-fold, and caused G0/G1 phase cell cycle arrest. Moreover, YM-155 treatment enhanced p53 expression, suggesting reactivation of tumor suppressor pathways. Notably, combining YM-155 and the chemotherapeutic agent etoposide resulted in synergistic inhibition of NB growth with ED75 values ranging from 0.17 to 1, compared to either agent alone. In the xenograft mouse model, YM-155 inhibited tumor burden in contrast to controls by about 3-fold, and without any notable toxic effects in vivo. Conclusion: Overall, our findings identify YM-155 as a promising therapeutic agent for high-risk NB by directly targeting survivin and enhancing chemosensitivity. These results support continued preclinical development of survivin inhibitors as part of rational combination strategies in pediatric cancer treatment. Full article

Childhood cancer treatments, including chemotherapy, radiation therapy, and combined modalities, pose significant risks to auditory function due to their ototoxic effects. Cisplatin, a chemotherapeutic agent commonly used in pediatric oncology, causes dose-dependent irreversible sensorineural hearing loss by damaging the inner ear structures, primarily through the generation of reactive oxygen species and the activation of apoptotic pathways. Radiation therapy exacerbates these effects, contributing to both sensorineural and conductive hearing loss via mechanisms such as vascular injury, inflammation, and fibrosis. The severity of hearing loss is influenced by the treatment timing, the cumulative dose, patient age, genetics, and concurrent therapies. The damaging effects of chemotherapy and radiation extend beyond the cochlea, involving the surrounding temporal bone as well as multiple levels of the auditory pathway. While pediatric patients may be candidates for bone-anchored hearing devices or cochlear implants, the need for serial imaging and the potential for implant-related MRI artifacts can complicate the timing of hearing rehabilitation. Moreover, the impact on the subcortical and cortical auditory structures may further influence the rehabilitation outcomes. This scoping review lays the foundation for future clinical and research efforts focused on the development of comprehensive pediatric guidelines for hearing preservation, monitoring, and rehabilitation, while also fostering multidisciplinary collaboration. Full article

Background: Hepatoblastoma is a rare malignant liver tumor that accounts for 1–2% of pediatric cancers. Despite its low incidence, it is a significant cause of cancer-related mortality in early childhood. Methods: This ecological study analyzed hepatoblastoma mortality in Brazilian children and adolescents (2008–2023) using data from the Mortality Information System (SIM/DATASUS). Mortality rates were calculated using official population estimates. Temporal trends were assessed using Prais-Winsten regression. Age and sex differences were analyzed using the chi-square test. Global mortality estimates (2008–2021) were obtained from the Global Burden of Disease Study for descriptive comparison. Results: A total of 267 deaths were recorded, most (66.7%) in children aged 0–4 years. Males accounted for 61.4% of cases. Although no significant mortality trends were observed for younger age groups, a significant annual decline was found among adolescents aged 15–19 years (Annual Percent Change (APC) = −38.4%, p = 0.016). Regional disparities were evident, with the Southeast presenting the highest number of deaths. Globally, the estimated number of deaths and age-specific mortality rate (ASMR) decreased over time, particularly among children under five. Conclusions: Hepatoblastoma remains a significant cause of mortality in early childhood. While Brazilian mortality rates remained stable in younger groups, mortality in adolescents showed a marked reduction. Global estimates suggest a progressive reduction in mortality. Full article

Background: T-cell receptor excision circles (TRECs) are measured in newborn screening programs in the United States to identify severe combined immunodeficiency (SCID). We hypothesized that relatively low TREC levels at birth, even within the normal range, could indicate compromised immunity and higher susceptibility to childhood cancers. Methods: We conducted a case–control study using linked data from the newborn screening programs and cancer registries in California and Texas to examine the association between TREC levels and risk of childhood cancer. The study included 2196 cancer cases and 10,980 controls from California and 1186 cancer cases and 5890 controls from Texas. Results: In California, acute myeloid leukemia cases had significantly lower TREC levels compared with their matched controls (p = 0.0051), while in Texas, acute lymphocytic leukemia cases had significantly higher TREC levels compared with their matched controls (p = 0.0034). However, each association was not replicated in the other state, and other cancer types did not show significant differences in TREC levels between cases and controls. Conclusions: We did not observe consistent associations between TREC levels at birth and childhood cancer risk. A possible explanation for the lack of more clear-cut differences in TREC levels between cases and matched controls might be the complex etiology of childhood cancers. The results underscore the need for longitudinal studies that incorporate additional immune biomarkers to understand the immunologic basis of childhood cancer development. Full article