Pediatric Cancer Therapy Research Articles

NURS-04. MUSIC THERAPY WITH CAREGIVERS FOR THOSE WITH PEDIATRIC BRAIN CANCER AND BRAIN TUMORS: A CRITICAL REVIEW OF THE LITERATURE AND RECOMMENDATIONS FOR FUTURE PROGRAMS

Abstract BACKGROUND Caregivers for those with pediatric brain cancer and brain tumors face significant challenges. During the course of treatment, pediatric brain cancer and brain tumor patients face not just the physical consequences of treatments, but the neurological effects as well. METHODS This critical review of the literature examines the effects of Music Therapy on Caregivers, Caregivers for cancer patients, and Caregivers for pediatric cancer patients. A literature review was specifically chosen with the intention of making recommendations for future program planning. Subjects explored include the psychological, physical, and financial impacts of caregiving. Additional concepts include personality traits of Caregivers and multicultural considerations in caregiving. The topics of brain cancer and the use of Music Therapy with patients are also explored. Special attention is given to Music Therapy for Caregivers for those with pediatric brain cancer and brain tumors. Main points under this headline also include Caregiver stressors, similarities and differences in multicultural caregiving, and the limited research available to Caregivers. RESULTS At the time the literature review, no research had been conducted in the area of Music Therapy and Caregivers for pediatric brain cancer and primary brain tumors. Music Therapy was proven, however, to be a significant non-pharmaceutical intervention for several areas, including anxiety and pain management. CONCLUSION The conclusion drawn was that more research is needed with Music Therapy and this particular population. Additionally, a basic framework for a Music Therapy program for Caregivers for those with pediatric brain cancer and brain tumors has been provided with recommendations on the expansion of the program.

Immune Microenvironment in Childhood Cancers: Characteristics and Therapeutic Challenges.

The tumor immune microenvironment is pivotal in cancer initiation, advancement, and regulation. Its molecular and cellular composition is critical throughout the disease, as it can influence the balance between suppressive and cytotoxic immune responses within the tumor's vicinity. Studies on the tumor immune microenvironment have enriched our understanding of the intricate interplay between tumors and their immunological surroundings in various human cancers. These studies illuminate the role of significant components of the immune microenvironment, which have not been extensively explored in pediatric tumors before and may influence the responsiveness or resistance to therapeutic agents. Our deepening understanding of the pediatric tumor immune microenvironment is helping to overcome challenges related to the effectiveness of existing therapeutic strategies, including immunotherapies. Although in the early stages, targeted therapies that modulate the tumor immune microenvironment of pediatric solid tumors hold promise for improved outcomes. Focusing on various aspects of tumor immune biology in pediatric patients presents a therapeutic opportunity that could improve treatment outcomes. This review offers a comprehensive examination of recent literature concerning profiling the immune microenvironment in various pediatric tumors. It seeks to condense research findings on characterizing the immune microenvironment in pediatric tumors and its impact on tumor development, metastasis, and response to therapeutic modalities. It covers the immune microenvironment's role in tumor development, interactions with tumor cells, and its impact on the tumor's response to immunotherapy. The review also discusses challenges targeting the immune microenvironment for pediatric cancer therapies.

Financial toxicity during pediatric cancer therapy: A qualitative analysis.

11056 Background: Childhood cancer treatment may often result in adverse financial consequences—also termed financial toxicity (FT)—for patients and families. Limited research has specifically examined mechanisms and drivers of FT salient to pediatric oncology. Methods: Using a phenomenological approach, we conducted in-depth interviews with a purposive sample of English- and Spanish-speaking parents of children receiving treatment for cancer at our institution. Parents were interviewed 6-18 months after a first cancer diagnosis, a period chosen to balance accumulation of financial challenges after treatment initiation with minimal recall bias. Interviews were coded by 3 investigators using an inductive, open-ended approach. We performed thematic analysis of interview transcripts focused on elucidating the main components of FT and relationships between them, identifying ameliorating and exacerbating factors, and exploring the impact of FT on patient and family well-being. We organized relationships between themes into a conceptual framework. Results: We interviewed 21 parents (86% mothers, 59% >40 years old, 33% non-Hispanic White, 47% college-educated, 42% of those reporting had a household income of $50-100k, equal proportions above/below this). We identified 5 themes. Four themes pertained to primary elements of FT: (1) increased out-of-pocket spending, often related to additional caregiving and household coordination needs; (2) reduced income, primarily from employment changes inadequately covered by paid leave; (3) new material hardship, with families unable to afford costs of living when previously able to do so; and (4) elevated psychological distress regarding finances. We also identified an additional theme pertaining to response behaviors directed at managing FT, effects of which could be positive (“adaptive behaviors”), negative (“maladaptive behaviors”), or mixed. Response behaviors included reducing discretionary spending, selling off assets, skipping meals, requesting money from strangers, and rummaging through discarded items. Several exacerbating and ameliorating factors pertinent to the development of FT emerged, including household location, composition, wealth, employment flexibility, resource provision, and duration and severity of treatment. Parents provided perspectives regarding policies or interventions to mitigate FT, such as toolkits to better connect families with financial resources and extended paid family leave. Conclusions: Families of children with cancer face a wide range of financial toxicity throughout treatment, and many of these experiences differ considerably from those of adult patients. Many families reported substantial impact and unmet needs. These findings will help inform the design of quantitative measures specific to pediatric cancer and identify unique targets for intervention development and policy change for children with cancer.

An analysis of muscle growth after proton beam therapy for pediatric cancer.

Retardation of growth and development is a well-known late effect after radiotherapy for pediatric patients. The goal of the study was to examine the effect of proton beam therapy (PBT) on the growth of muscles included in the irradiated area. The subjects were 17 pediatric patients (age ≤ 5years) who received PBT with a treatment field including a muscle on only one side out of a pair of symmetrical bilateral muscles and had imaging evaluations for at least 1year after PBT. The thicknesses of the irradiated and non-irradiated (contralateral) muscles were measured retrospectively on CT or MRI axial images collected before and after PBT. The change of thickness divided by the period (years) for each muscle was compared between the irradiated and contralateral sides. Correlations of muscle growth with irradiation dose and age at the start of treatment were also evaluated. The median observation period was 39.2months. The measurement sites included the erector spinae (n = 9), gluteus maximus (n = 5) and rhomboids + trapezius (n = 3) muscles. The average changes in muscle thickness were 0.24mm/year on the irradiated side and 1.19mm/year on the contralateral side, showing significantly reduced growth on the irradiated side (P = 0.001). Younger patients had greater muscle growth. Irradiation dose was not significant, but muscle growth tended to decrease as the dose increased, and muscles irradiated at >50Gy (RBE) showed little growth. These results show that muscle growth is affected by PBT and that long-term follow-up is needed to evaluate muscle growth retardation.

Yoga versus iPad active control for fatigue in paediatric cancer therapy: a randomised controlled trial

ObjectivesThe primary objective was to determine if individualised yoga for hospitalised children receiving intensive chemotherapy was associated with less fatigue using the Pediatric Quality of Life Inventory Multidimensional Fatigue Scale...

Global Distribution of Clinical Trials on Chimeric Antigen Receptor T-Cells in the Pediatric Population: The Economic Impact on Clinical Trials Development

Keywords: Chimeric Antigen Receptor T cell, Pharmacoeconomic, Pediatric, Clinical Trials With the success of Chimeric Antigen Receptor (CAR) T-cell therapy in the pediatric population, new clinical trials have surged worldwide. To date, no previous study has analyzed the effect of socioeconomic factors on the development of clinical trials for CAR T-cells in the pediatric population. In recent years new countries and emerging economies have contributed significantly to the development of CAR T-cell clinical trials. A better understanding of the socioeconomic factors that influenced these trends will facilitate the future development of this cellular therapy field. To assess the impact of socioeconomic factors related to the development of clinical trials on CAR T-cell therapies in the pediatric population, we analyzed data entries from clinical trials registered to the Clinicaltrials.gov database. To query the information, we used the following keywords “(leukemia OR cancer OR lymphoma OR malignancies OR tumor OR solid tumor) AND (CAR OR chimeric antigen receptor OR CAR T-cell OR adoptive immunotherapy OR immune effector OR cellular therapy) AND (Child)”. In addition, we used different filters that allowed the selection of studies that focused on patients 18 years of age and younger. Data corresponding to entries with a data cut-off of July-2023 were included. In addition, we use the World Bank country's macroeconomic database (January 1 st, 2009 to December 31 st, 2022). We found 4,297 results in the Clinicaltrials.gov platform; we excluded 3,978 clinical trials that did not involve the pediatric population (≤18 years) or CAR T-cell intervention. There were 319 clinical trials included, sponsored in 19 countries, as shown in Figure A. Of those studies, 207 (64.9%) were conducted in China, 74 (23.2%) in the U.S., and 21 (6.5%) in Europe. Not surprisingly, the number of clinical trials is strictly proportional to each country's Gross Domestic Product (GDP) and Research and Development (R&D) expenditure, as shown in Figure B. Pearsons' coefficient between GDP and the number of trials registered per country is 0.8 (p-value < 0.001); similarly, Pearsons's coefficient between R&D expenditure and the number of problems reported per country is 0.64 (p-value < 0.004). The United States and China are developing 88% of the Clinical trials, and 96% of the clinical trials occur in countries ranked in the top 10 highest GDP. Our database analysis shows a notable disparity in the countries leading cutting-edge research in CAR T-cell therapy for pediatric oncology. The primary locations for these clinical studies are countries ranked in the top 10 in terms of GDP, with China and the USA being the main contributors. Access to clinical trials plays a crucial role in improving cancer patients' outcomes, and this disparity in the development of cellular therapies is likely to impact children from middle and low-GDP countries significantly. Urgent strategies are required to address this issue and ensure more equitable access to advanced technologies and clinical trials in cellular therapy for pediatric cancers. These strategies should become a high priority for national and international health departments and organizations in the coming years. By promoting more comprehensive clinical trial access and collaboration, we can work towards reducing these disparities and providing better treatment options for all children facing pediatric cancer.

Clinical Trials on Cellular Therapy for Children and Adolescents With Cancer: A 15-Year Trend in the United States.

Cellular therapies are frequently studied in clinical trials for pediatric patients with malignant disease. Characteristics of ongoing and completed cellular therapy clinical trials in the U.S. involving children and adolescents have not previously been reported. We searched ClinicalTrials.gov for clinical trials involving cellular therapies enrolling patients under 18 years of age in the U.S. Trials were initially stratified into child-only (maximum age of eligibility <18 years), child/adolescent and young adult (AYA)(maximum age of eligibility ≤21 years), and child/adult (maximum age of eligibility >21 years). Descriptive characteristics and trends over time were analyzed. We included 202 trials posted 2007-2022. Of the 202 trials, only three trials were child-only; thus, our subsequent analysis focused on comparing child/AYA (≤21 years) and child/adult trials (>21 years). One hundred sixty-nine (84%)enrolled both child and adult populations. The vast majority of trials were early phase (phase 1, 1/2, and 2, 198/202, 98%). Chimeric antigen receptor T cell therapies were most commonly studied (88/202, 44%), while natural-killer cell therapies were most common in child/AYA trials (42% vs. 16%). Most trials were single institution-only (130/202, 64%) and did not receive industry funding (163/202, 81%). Studies with industry funding were more likely to be multicenter (64% vs. 29%) and international (31% vs. 0.6%). Notably, no central nervous system tumor-specific trials had industry funding. There was no difference in therapy type based on funding source. Yearly new trial activations increased over the time period studied (p=0.01). The frequency of cellular therapy trial activations enrolling child/AYA patients with cancer in the U.S. has increased over time. Most studies were phase 1 or 2, single institution-only, and not industry-supported. Future opportunities for cell therapy for pediatric cancer should include multi-institutional approaches.

Improving quality and quantity of life for childhood cancer survivors globally in the twenty-first century.

The contributions of cooperative groups to performing large-cohort clinical trials and long-term survivorship studies have facilitated advances in treatment, supportive care and, ultimately, survival for patients with paediatric cancers. As a result, the number of childhood cancer survivors in the USA alone is expected to reach almost 580,000 by 2040. Despite these substantial improvements, childhood cancer survivors continue to have an elevated burden of chronic disease and an excess risk of early death compared with the general population and therefore constitute a large, medically vulnerable population for which delivery of high-quality, personalized care is much needed. Data from large survivorship cohorts have enabled the identification of compelling associations between paediatric cancers, cancer therapy and long-term health conditions. Effectively translating these findings into clinical care that improves the quality and quantity of life for survivors remains an important focus of ongoing research. Continued development of well-designed clinical studies incorporating dissemination and implementation strategies with input from patient advocates and other key stakeholders is crucial to overcoming these gaps. This Review highlights the global progress made and future efforts that will be needed to further increase the quality and quantity of life-years gained for childhood cancer survivors.

Abstract 3541: Tumoroid-based screening platform to test focal, chemo- and combination therapy for retinoblastoma

Abstract Current treatments for retinoblastoma, the most common intraocular malignancy, rely on a limited number of drugs repurposed from other pediatric cancer therapies. Drug toxicity and relapse of the disease necessitate new therapeutic strategies. The implementation of drug candidates in the clinic is usually followed by in vitro validation, which requires accurate and clinically relevant in vitro models. We report here a robust 3D tumoroid-based platform, for testing various clinical protocols, e.g. therapeutic agents following a single or repeated exposure, alone or in combination with focal therapy (thermotherapy). The platform, generated from the Y79 retinoblastoma cell line, consists of matrix-embedded tumoroids, which retain the key features of the disease and allow prolonged culture time. Following the optimization of growth conditions, the effect of single and repeated exposure to chemotherapeutic agents has been measured by high-throughput automated fluorescence imaging followed by quantification. The clinical conditions of chemothermotherapy have been recapitulated with a setup consisting of: an infrared diode laser (810 nm, 0.3 W) that heats the tumoroids in the presence of indocyanine green (50 µg/mL); a thermal camera to enable real-time temperature measurement; and an environment-controlled inverted microscope to ensure physiological conditions and precise focusing of the laser. Melphalan and carboplatin, two drugs currently used to treat retinoblastoma in clinical protocols of chemotherapy and chemothermotherapy respectively, have been applied to validate the system.Tumoroid viability and size progressively decreased over 4 weeks of repeated drug exposure with melphalan, reflecting the response of retinoblastoma in advanced clinical cases. Carboplatin treatment showed an activity enhancement in the tumoroid model similar to that observed in the clinic, when combined with focal therapy, demonstrating that the platform system closely recapitulates the clinical conditions. Inversely, the thermotherapy experimental protocol designed for 2D in vitro cell culture and commonly used to date, i.e. an incubation temperature increased to 42 °C for 1 h, did not show an improvement of the carboplatin cytotoxicity, confirming that our laser-based thermotherapy protocol provides a more accurate and clinically relevant drug response. Such an approach, combining physiologically relevant in vitro cancer models and investigation of drugs in well-established treatment modalities, can significantly reduce the number of new drug candidates that give false-positives or overestimated efficacies when evaluated in relevant in vivo models. It is expected that the platform will contribute to the implementation of new therapeutic strategies to treat retinoblastoma, and could also be adapted to other diseases for which repeated drug exposure and/or chemothermotherapy is relevant. Citation Format: Irina Sinenko, Fabien Kuttler, Valentin Simeonov, Alexandre Moulin, Christina Stathopoulos, Gerardo Turcatti, Adeline Berger, Francis Munier, Paul Dyson. Tumoroid-based screening platform to test focal, chemo- and combination therapy for retinoblastoma. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3541.

Abstract 3554: Targeting chromatin remodeling complex in pediatric cancers

Abstract Chromatin accessibility plays critical roles in maintaining normal gene regulatory programs in healthy tissue. Aberrant chromatin accessibility triggered by abnormal activity of a variety of chromatin remodeling complexes is known to activate and maintain tumor proliferation. The most widely known of these complexes is the SWI/SNF (also called BAF) complex. Studies have shown that BAF regulates chromatin accessibility in a more global manner and its long-term inhibition or functional loss may lead to non-specific downstream effects in both tumor and normal tissue. Thus, there is a need to further probe understudied complexes, such as the Imitation Switch (ISWI) family of chromatin remodelers, to find more cancer specific functions that can provide mechanistic insights that pave the way for novel therapeutic discoveries. We have examined the functions of these chromatin complex in different type of pediatric cancers to estsablish the pre-clinical rationale for potential novel pediatric cancer therapy. We discovered that fusion protein positive rhabdomyosarcoma (FP-RMS), an aggressive sub-type of RMS characterized by chromosomal translocations resulting in gene fusions between PAX3/7 and FOXO1 is highly dependent on chromatin accessibility. This aggressive subtype exhibits a significant vulnerability in its dependence on the oncogenic transcription factor PAX3-FOXO1, yet like many other TFs, PAX3-FOXO1 is currently not considered a viable therapeutic candidate. We have then carefully examined the effect of chemical inhibition and chemical degradation of BAF complex function in FP-RMS and discovered that BAF complex globally regulates chromatin accessibility, is not specifically regulating FP function. We next examined the function of other chromatin remodeling complexes that might regulate FP function specifically in FP-RMS. We identified that some of other chromatin remodeling complex, such as Nuclear Remodeling Factor (NURF) complex, a member of the ISWI chromatin remodeling complex family, interacts with a critical fusion protein, PAX3/7-FOXO1, in FP-RMS. There is limited understanding surrounding the functions of NURF complex, particularly in pediatric cancer. Here, we then studied the key functions of FP regulated by variety of chromatin remodeling complex utilizing combined chemistry and biology method to elaborate the essential functions of PAX3/7-FOXO1 fusion protein. We have developed variety of chemical strategies to target these complexes, and utilize these tool compounds to delineate the chromatin remodeling complex regulated FP functions. This study showcased our approach to advance cancer research by combining the power of chemistry, chemical biology, structural biology, computational biology and cellular biology to identify novel mechanistic understanding as well as novel therapeutic approach for pediatric cancers. Citation Format: Jun Qi. Targeting chromatin remodeling complex in pediatric cancers. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3554.

Invited Commentary on Vasudevan, et al: Outcomes of children with well differentiated fetal hepatoblastoma treated with surgery only: Report from Children's Oncology Group Trial, AHEP0731

Advances in hepatoblastoma treatment have improved survival but have been accompanied by the chronic toxicities of pediatric cancer therapy. Cisplatin is the cornerstone of chemotherapy treatment for hepatoblastoma. The most frequent long-term complication of hepatoblastoma treatment is cisplatin-related ototoxicity. Among children who receive cisplatin, 25-90% will exhibit measurable hearing loss, impacting language and social development [1]. Therefore, efforts to identify children eligible for reduction or elimination of cisplatin-based chemotherapy while maintaining excellent oncologic outcomes are paramount in reducing the long-term toxicities of hepatoblastoma cancer treatment.

Medulloblastoma: Immune microenvironment and targeted nano-therapy

The tumor microenvironment (TME) plays key roles in tumor development, progressive and metastasis. Recently, therapy strategies based on TME targeted modulation shows potential to improve the efficacy of therapeutics, which attracted much attention in pediatric brain cancer therapy. Moreover, the advanced technology on carrier design and drug formulation improved the penetrated efficiency and TME specific targeting delivery of nanoparticles for TME specific modulation. In this review, we briefly introduce the microenvironment substitutes in medulloblastoma (MB) including dendritic cells, macrophages, tumor vasculature and tumor-draining lymph nodes. In addition, we review various nano-based drug delivery strategies targeting these TME components and their applications in tumor therapy.

The toll of transition: Caregiver perceptions of family adjustment during the transition off pediatric cancer therapy.

The role of transition-focused psychology appointments in managing the transition off therapy is unclear. The objective of this research was to explore caregiver perceived familial distress and the role of psychology in preparing families for transition. Fifty-seven caregivers of youth, who finished treatment, completed an online questionnaire through a quality improvement project on experiences of families at transition. Twenty-two percent of caregivers had children who completed a transition-focused psychology consult and 63% completed a cognitive assessment at transition. Retrospective analyses were conducted assessing the association of psychology visits on caregiver perceptions of being informed of and prepared to manage transition-related challenges. Most caregivers reported experiencing adjustment concerns for family members. Caregivers of children completing a transition-focused psychology consult or cognitive assessment reported feeling more informed and greater preparedness to manage difficulties. Although decreased distress was not associated with the visit, those who felt more informed and prepared reported lower distress. Caregivers perceive transitioning off therapy as stressful for their family, though they experience decreased familial distress when informed of and prepared to manage transition-related challenges. These findings highlight the importance of psychosocial support at transition.

Nanoparticles for Diagnosis and Target Therapy in Pediatric Brain Cancers.

Pediatric brain tumors represent the most common types of childhood cancer and novel diagnostic and therapeutic solutions are urgently needed. The gold standard treatment option for brain cancers in children, as in adults, is tumor resection followed by radio- and chemotherapy, but with discouraging therapeutic results. In particular, the last two treatments are often associated to significant neurotoxicity in the developing brain of a child, with resulting disabilities such as cognitive problems, neuroendocrine, and neurosensory dysfunctions/deficits. Nanoparticles have been increasingly and thoroughly investigated as they show great promises as diagnostic tools and vectors for gene/drug therapy for pediatric brain cancer due to their ability to cross the blood–brain barrier. In this review we will discuss the developments of nanoparticle-based strategies as novel precision nanomedicine tools for diagnosis and therapy in pediatric brain cancers, with a particular focus on targeting strategies to overcome the main physiological obstacles that are represented by blood–brain barrier.

Epigenetics of pediatric liver cancer and potential therapy

The pediatric liver cancer hepatoblastoma (HBL) has a complex etiology which is not yet determined.In contrast to adult liver cancer hepatocellular carcinoma (HCC), pediatric HBL has a low rate of genetic mutations suggesting that other mechanisms play a critical role in development of this disease

Newly identified chemotherapy-induced peripheral neuropathy in a childhood cancer survivorship clinic.

Chemotherapy-induced peripheral neuropathy (CIPN), a debilitating side effect of pediatric cancer therapy, can be challenging to diagnose. We estimated the prevalence of newly identified and previously diagnosed CIPN in the regional HEROS Childhood Cancer Survivorship Clinic. From 2016 to 2018, 148 survivors (45.3% female, age 17.1 [SD 7.7]years, 81.8% in ongoing routine oncology follow-up) had their initial survivorship evaluation at an average of 7.4 (SD 6.6)years from diagnosis. Fifty-six survivors (37.8%) had CIPN, of these 46 (82.1%) were newly identified. Our findings demonstrate CIPN may be missed in routine oncology care, and new methods are needed to screen for CIPN.

Baseline nutrition in pediatric cancer therapy: A potential game changer

Baseline nutrition in pediatric cancer therapy: A potential game changer

Improving Guideline-Congruent Care for Chemotherapy-Induced Nausea and Vomiting Prophylaxis in Pediatric Oncology Patients.

Chemotherapy-induced nausea and vomiting (CINV) is a very common side effect of pediatric cancer therapy. High-quality, evidence-based, pediatric-specific guidelines for prophylaxis and treatment of CINV are available. At many centers, guideline-concordant care is uncommon. We formed a multidisciplinary quality improvement team to implement guideline-concordant care for CINV prophylaxis at our center. We present the results following the first year of our interventions. We planned and implemented a multipronged approach in three key phases: (1) developing and publishing an acute CINV prophylaxis pathway, (2) education of providers, and (3) updating the computerized provider order entry system. We used iterative, sequential Plan-Do-Study-Act cycles and behavioral economic strategies to improve adherence to guideline-concordant CINV prophylaxis. We focused on aprepitant usage as a key area for improvement. At the beginning of the study period, < 50% of patients were receiving guideline-concordant CINV prophylaxis and < 15% of eligible patients were receiving aprepitant. After 1 year, more than 60% of patients were receiving guideline-concordant care and 50% of eligible patients were receiving aprepitant. We describe the development and implementation of a standardized pathway for prevention of acute CINV in pediatric oncology patients. With a multidisciplinary, multifaceted approach, we demonstrate significant improvements to guideline-congruent CINV prophylaxis.

Assessment of Neurocognitive Functions in Children Treated for Cancer

Background: About eight percent of adults and children who receive a cancer diagnosis today are projected to live at least 5 years thanks to advancements in pediatric cancer therapy over the last several decades. More than half a million people will have survived childhood cancer by 2020, according to current estimates. Objective: To evaluate the association between childhood cancer, antineoplastic treatment and neurocognitive dysfunction. Patients and Methods: In the Pediatrics Department of the Faculty of Medicine at Zagazig University, a case control study was undertaken on 25 cancer patients who had completed their treatment and on 25 healthy children between August 2020 and July 2021. Children of both sexes, aged 5-15, were enrolled in the study. Results: In terms of full and performance intelligence quotient (IQ) scale, there was statistically significant difference between the groups (much higher in the control group), but the verbal scale did not differ statistically between the groups. Regarding verbal IQ, there was no statistically significant difference between the groups examined. However, there were no significant differences in IQ subtests for information, vocabulary, arithmetic, comprehension, picture completion, mazes or block design between groups. Control group was significantly higher as regard similarity and geometric design. Conclusions: Neurocognitive function is affected in cancer survivors of children as there is statistically significant difference between the studied groups regarding full, and performance IQ scale (significantly higher in control group) but verbal scale was not statistically different between the groups.

Xenograft models for pediatric cancer therapies.

The prognosis for childhood cancer has improved considerably over the past 50 years. This improvement is attributed to well-designed clinical trials which have incorporated chemotherapy, surgery, and radiation. With an increased understanding of cancer biology and genetics, we have entered an era of precision medicine and immunotherapy that provides potential for improved cure rates. However, preclinical evaluation of these therapies is more nuanced, requiring more robust animal models. Evaluation of targeted treatments requires molecularly defined xenograft models that can capture the diversity within pediatric cancer. The development of novel immunotherapies ideally involves the use of animal models that can accurately recapitulate the human immune response. In this review, we provide an overview of xenograft models for childhood cancers, review successful examples of novel therapies translated from xenograft models to the clinic, and describe the modern tools of xenograft biobanks and humanized xenograft models for the study of immunotherapies.