CURE Childhood Cancer

HighlightsWhat are the main findings?Non-communicable diseases (NCDs) impact 2.1 billion children worldwide and cause nearly 1 million deaths annually, with poor nutritional status further in-creasing mortality and treatment-related complications.Integrating nutrition care into childhood NCD management improves survival, reduces treatment-related complications, influences disease progression, and lowers healthcare costs.What is the implication of the main finding?Nutrition services should be embedded as a standard component of NCD care for children, yet underfunding, workforce shortages, inadequate training, and limited access to nutrition products continue to hinder progress.Multi-sectoral collaboration is essential to expand the nutrition workforce, strengthen training and professional standards, establish effective monitoring frameworks, and leverage technology to deliver sustainable solutions.Non-communicable diseases (NCDs) affect over 2.1 billion children globally, accounting for 15.9% of deaths in children under 20 and contributing 174 million years lived with disability. Integrating nutrition care into NCD management within health systems can save lives, reduce costs, and improve quality of life. Nutrition interventions have been found to improve survival rates in children with cancer by 30%. Incorporating early nutrition interventions in hospitals is associated with a 36% reduction in per-patient costs. Despite these clear benefits, nutrition care is often not readily accessible as part of NCD management in children. Access to trained nutrition professionals is limited, and nutrition training for healthcare workers is often inadequate. There are cost-effective and scalable models for delivering high-quality nutrition care, but scaling these models will require commitment to capacity building, training, technological innovation, and monitoring frameworks. Coordinated, multisectoral responses are needed urgently to incorporate nutrition sustainably into healthcare systems to confront the growing burden of childhood NCDs.

This article gives a detail information on the relationship between emotional intelligence and psychological distress keeping in mind the moderating role of adverse childhood experiences. The respondents were the university students of Pakistan from various universities across the four provinces. A sample size was 430. Validated scales were used for this study and permission was taken from the authors. The outcomes proved that relationship between the emotional intelligence and psychological distress is strengthened by the adverse childhood experiences. This study will help the university policy makers to improve the mental health policies of the students. It will also help to identify the increase of psychological distress due to the early childhood experiences.

Childhood cancer survivors (CCSs) face long-term health challenges, yet the health and specific needs of Latin American survivors remain underexplored. This study aimed to describe the health-related, psychosocial late effects, and information needs among CCSs in the region. This mixed-method study combined quantitative data from an online survey with qualitative insights from follow-up interviews, involving CCSs from the largest regional survivor network and additional participants recruited through snowball sampling. We report the quantitative results here. The survey was adapted from the Childhood Cancer Survivor Study Survey Follow-Up and the Needs Assessment Questionnaire (CCSS-NAQ). A total of 135 CCSs from 16 Latin American countries participated (mean age 26.1 years). The most frequent late effects were mental health (61.2%), endocrine (58.6%), and cardiovascular (42.1%). Infertility was prevalent (16.9%), with nearly one-third unsure of their fertility status. Anxiety (51.1%) and depression (31.8%) were common. Significant findings included higher rates of endocrine disorders in females (p = 0.0018) and those who had received radiation (p = 0.048), respiratory problems in stem cell transplantation recipients (p = 0.026), and auditory impairment in survivors of a solid tumor (p = 0.0031). While most felt informed about their health, only one-third had regular medical follow-up and access to psychological care. Survivors expressed a strong interest in learning more about fertility and mental health, with a preference for digital information. The study documents the need for region-specific survivorship care that addresses both the physical and mental health challenges of Latin American CCSs.

Background: Cancer and its treatments can affect dental health of childhood cancer survivors. We aimed to evaluate prevalence of dental problems in survivors, compare them to their siblings, and investigate cancer-related risk factors. Methods: As part of the population-based Swiss Childhood Cancer Survivors Study, we sent questionnaires inquiring about dental problems to survivors aged 5-19 years and their siblings. We retrieved cancer-relevant information from the Swiss Childhood Cancer Registry and used logistic regressions to compare dental problems between survivors and siblings and to investigate cancer-related risk factors. Results: We included 735 survivors and 144 siblings. Almost half of survivors and siblings reported at least one dental problem. Compared to siblings, survivors had a greater risk for hypo- or microdontia (OR 1.7; 95%CI 0.9-3.2) and enamel hypoplasia (2.2; 0.8-6.0), but similar risk for cavities or cavity-related tooth loss (0.8; 0.6-1.3). Chemotherapy was associated with enamel hypoplasia (3.0; 1.2-10.4), cavities or cavity-related tooth loss (1.5; 1.0-2.3), and gum problems during (23.0; 9.4-76.2) and after (4.6; 2.0-13.5) treatment. Hematopoietic stem cell transplantation (HSCT) was related to hypo- or microdontia (5.4; 2.6-10.7), cavities or cavity-related tooth loss (2.1; 1.2-3.6), and gum problems during treatment (2.0; 1.2-3.6). For hypo- or microdontia and cavities, associations with treatment were driven by patients diagnosed <5 years. Conclusion: Childhood cancer patients treated with chemotherapy or HSCT, especially at a young age, were at higher risk for dental problems. Regular dental check-ups guided by healthcare teams and dental hygiene habits can mitigate risks and promote long-term dental health of survivors.

Survival of Wilms tumor (WT) is>90% in high-resource settings but<30% in low-resource settings. Adapting a standardized surgical approach to WT is challenging in low-resource settings, but a local control strategy is crucial to improving outcomes. Provide resource-sensitive recommendations for the surgical management of WT. We performed a systematic review of PubMed and EMBASE through July 7, 2020, and used the GRADE approach to assess evidence and recommendations. Initiation of treatment should be expedited, and surgery should be done in a high-volume setting. Cross-sectional imaging should be done to optimize preoperative planning. For patients with typical clinical features of WT, biopsy should not be done before chemotherapy, and neoadjuvant chemotherapy should precede surgical resection. Also, resection should include a large transperitoneal laparotomy, adequate lymph node sampling, and documentation of staging findings. For WT with tumor thrombus in the inferior vena cava, neoadjuvant chemotherapy should be given before en bloc resection of the tumor and thrombus and evaluation for viable tumor thrombus. For those with bilateral WT, neoadjuvant chemotherapy should be given for 6-12weeks. Neither routine use of complex hilar control techniques during nephron-sparing surgery nor nephron-sparing resection for unilateral WT with a normal contralateral kidney is recommended. When indicated, postoperative radiotherapy should be administered within 14 days of surgery. Post-chemotherapy pulmonary oligometastasis should be resected when feasible, if local protocols allow omission of whole-lung irradiation in patients with nonanaplastic histology stage IV WT with pulmonary metastasis without evidence of extrapulmonary metastasis. We provide evidence-based recommendations for the surgical management of WT, considering the benefits/risks associated with limited-resource settings.

We investigated whether targeting chromatin stability through a combination of the curaxin CBL0137 with the histone deacetylase (HDAC) inhibitor, panobinostat, constitutes an effective multimodal treatment for high-risk neuroblastoma. The effects of the drug combination on cancer growth were examined in vitro and in animal models of MYCN-amplified neuroblastoma. The molecular mechanisms of action were analyzed by multiple techniques including whole transcriptome profiling, immune deconvolution analysis, immunofluorescence, flow cytometry, pulsed-field gel electrophoresis, assays to assess cell growth and apoptosis, and a range of cell-based reporter systems to examine histone eviction, heterochromatin transcription, and chromatin compaction. The combination of CBL0137 and panobinostat enhanced nucleosome destabilization, induced an IFN response, inhibited DNA damage repair, and synergistically suppressed cancer cell growth. Similar synergistic effects were observed when combining CBL0137 with other HDAC inhibitors. The CBL0137/panobinostat combination significantly delayed cancer progression in xenograft models of poor outcome high-risk neuroblastoma. Complete tumor regression was achieved in the transgenic Th-MYCN neuroblastoma model which was accompanied by induction of a type I IFN and immune response. Tumor transplantation experiments further confirmed that the presence of a competent adaptive immune system component allowed the exploitation of the full potential of the drug combination. The combination of CBL0137 and panobinostat is effective and well-tolerated in preclinical models of aggressive high-risk neuroblastoma, warranting further preclinical and clinical investigation in other pediatric cancers. On the basis of its potential to boost IFN and immune responses in cancer models, the drug combination holds promising potential for addition to immunotherapies.

Here we propose a vaccination strategy for SARS-CoV-2 based on identification of both highly conserved regions of the virus and newly acquired adaptations that are presented by MHC class I and II across the vast majority of the population, are highly dissimilar from the human proteome, and are predicted B cell epitopes. We present 65 peptide sequences that we expect to result in a safe and effective vaccine which can be rapidly tested in DNA, mRNA, or synthetic peptide constructs. These include epitopes that are contained within evolutionarily divergent regions of the spike protein reported to increase infectivity through increased binding to the ACE2 receptor, and within a novel furin cleavage site thought to increase membrane fusion. This vaccination strategy specifically targets unique vulnerabilities of SARS-CoV-2 and should engage a robust adaptive immune response in the vast majority of the human population.

Abstract Treatment-induced high-grade gliomas (TIHGGs) are an incurable late complication of cranial radiation therapy or combined radiation/chemotherapy used to treat pediatric cancer. We assembled a cohort of 33 TIHGGs from multiple institutions. The primary antecedent malignancies were medulloblastoma, acute lymphoblastic leukemia, astrocytoma, and ependymoma. We performed methylation profiling, RNA-seq, and genomic sequencing (whole-genome or whole-exome) on TIHGG samples. Methylation profiling revealed that TIHGGs cluster primarily with the pediatric receptor tyrosine kinase I subtype (26/31 samples). Common TIHGG copy-number alterations include Chromosome (Ch.) 1p loss/1q gain, Ch. 4 loss, Ch. 6q loss, and Ch. 13 and Ch. 14 loss; focal alterations include PDGFRA and CDK4 gain and loss of CDKN2A and BCOR. Relative to de novo pediatric high-grade glioma (pHGG), BCOR loss (p=0.004) and CDKN2A loss (p=0.005) were significantly increased. Transcriptomic analysis identified two distinct TIHGG subgroups, one with a lesser mutation burden (0.12 mut/Mb), Ch. 1p loss/1q gain (5/6 samples), and stem cell characteristics, and one with a greater mutation burden (1.08 mut/Mb, p&lt;0.0002), depletion of DNA repair pathways, and inflammatory characteristics. We observed increased chromothripsis in TIHGG versus pHGG (67% vs. 31%, p=0.036), which was associated with extrachromosomal circular DNA-mediated amplification of PDGFRA and CDK4. In vitro drug screening in one primary, patient-derived TIHGG cell line from each expression subgroup identified microtubule inhibitors/stabilizers, DNA-damaging agents, MEK inhibition, and, in the inflammatory subgroup, proteasome inhibitors as potentially effective therapies. This study provides a comprehensive molecular profile of TIHGG, including mechanistic insights to TIHGG oncogenesis, and identifies potentially effective therapeutic modalities for further investigation.

Tumor infiltration by lymphocytes has been linked to improved clinical outcome in children with neuroblastoma (NB) but T-cell activation has never been demonstrated to occur within the NB microenvironment. Here we show that tumor-associated lymphocytes (TALs) obtained from lesions representing all genetic subsets of NB and autologous peripheral blood lymphocytes (PBLs) analyzed on the day of tumor excision differed in composition, phenotype and functional characteristics. The NB microenvironment appeared to promote the accumulation of CD3+CD8+ T cells and contained a larger proportion of T cells expressing the interleukin-2 receptor α chain (CD25) and manifesting an effector memory (CCR7−CD45RA−) phenotype. Accordingly, the stimulation of PBLs with autologous tumor cells in short-term cultures increased the proportion of effector memory T cells, upregulated CD25, stimulated the expression of the TH1 cytokines interferon γ and tumor necrosis factor α, and reduced the expression of transforming growth factor β. In situ proliferation as well as a characteristic pattern of T-cell receptor aggregation at the contact sites with malignant cells was revealed by the immunohistochemical staining of TALs in primary tumors, indicating that the NB milieu is compatible with the activation of the immune system. Our results are compatible with the hypothesis that CD8+ T cells are specifically activated within the NB microenvironment, which appears to be permissive for effector memory responses.

Journal Article Heritability of Wilms' Tumor Get access Michael M. Hawkins, Michael M. Hawkins Childhood Cancer Research Group, University of OxfordU.K. Search for other works by this author on: Oxford Academic PubMed Google Scholar David L. Winter, David L. Winter Childhood Cancer Research Group, University of OxfordU.K. Search for other works by this author on: Oxford Academic PubMed Google Scholar Hazel S. Burton, Hazel S. Burton Childhood Cancer Research Group, University of OxfordU.K. Search for other works by this author on: Oxford Academic PubMed Google Scholar Michael H. N. Potok Michael H. N. Potok * Childhood Cancer Research Group, University of OxfordU.K. Correspondence to : Michael M. Hawkins, D.Phil., Childhood Cancer Research Group, University of Oxford, 57 Woodstock Rd., Oxford OX2 6HJ, U.K. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 87, Issue 17, 6 September 1995, Pages 1323–1324, https://doi.org/10.1093/jnci/87.17.1323 Published: 06 September 1995 Article history Received: 30 March 1995 Revision received: 13 June 1995 Accepted: 21 June 1995 Published: 06 September 1995