Pediatric Cancer Patients Research Articles

Abstract 14368: FAPI-PET Imaging Detects Anthracycline-Induced Cardiotoxicity Before Echocardiography

Introduction: We aimed to validate a PET imaging biomarker for the detection of incipient anthracycline-induced cardiotoxicity. This condition affects >5% of all pediatric cancer patients, leading to long-term health deficits. We hypothesized that fibroblast activation protein (FAP) would be a suitable candidate due to its role in extracellular matrix remodeling and fibrosis during early cardiac injury and the availability of high-affinity PET probes. Methods: Cardiotoxicity was established in male C57BL/6J mice by administering a cumulative 24 mg/kg dose of doxorubicin (DOX) intraperitoneally over 2 weeks [1]. The DOX mice were imaged serially with echocardiography and [68Ga]Ga-FAPI-04 PET over 12 weeks and compared to age- and sex-matched controls. Fractional shortening (FS) was determined from the echocardiograms, and cardiac uptake of [68Ga]Ga-FAPI-04 was quantified and expressed as percent injected dose per cubic centimeter (%ID/cm3). Heart tissue samples were collected and used for the analysis of bulk RNA-seq, RT-qPCR, Western blot, in situ hybridization (ISH), and histological staining. Finally, we used the DAVID tools and STRING database to confirm the relationship between PET signal and gene expression. Results: DOX mice exhibited decreased body weight (33% by 9 weeks after end-of-treatment) and heart weight-to-tibia length ratio (HW/TL, 39%). Cardiac [ 68 Ga]Ga-FAPI-04 PET signal was significantly higher (1.7-fold) in DOX mice from 2 weeks through the study endpoint. By contrast, no cardiac dysfunction was evident by echocardiography until 10 weeks after end-of-treatment, at which point FS was significantly reduced relative to the control group (30%). Transcription and translation of FAP were elevated in the DOX hearts, in agreement with the PET data. In the heatmap generated from the RNA-seq data, genes related to cell adhesion and extracellular remodeling were significantly upregulated in the DOX mice relative to controls. The H-score of FAP ISH was linearly related to the cardiac signal of [ 68 Ga]Ga-FAPI-04 PET (p = 0.001). Conclusions: FAP is a suitable imaging biomarker for cardiotoxicity and FAPI-PET is a promising tool for identifying patients at risk of cardiotoxicity during or after anthracycline chemotherapy.

Realities and ideals: Experiences and needs of pediatric oncology nurses in communication processes with children and their families at the end‐of‐life period: A photovoice qualitative study

AbstractEffective communication in end‐of‐life care for pediatric cancer patients is crucial. Yet, limited research focuses on the communication experiences of pediatric oncology nurses during this period. This study aims to investigate the communication experiences and needs of these nurses with children and their families during the end‐of‐life period. A qualitative study design with photo voice methodology was followed. The research was conducted with 16 pediatric oncology nurses working in the pediatric oncology wards of a university hospital between January and May 2023. Data were collected the “Characteristic Information Form”, “Semi‐Structured Interview Form”, and photovoice methodology. Data were analyzed through reflexive thematic analysis. Most of the nurses are at the undergraduate level, and their working experience in pediatric oncology wards ranges from 4 months to 17 years. Seven main themes emerged: Optimistic Communication‐Interaction, Mindfulness, Active Coping, Behavioral Actions, Death Uncertainty Dilemma, Interpersonal and Environmental Factors, and Discrepancy between Ideals and Reality. The study sheds light on the importance of pediatric oncology nurses' ideals versus realities upstream approach in communicating with end‐of‐life children and their families, empowering pediatric oncology nurses on the journey to ideal end‐of‐life care.

Posterior reversible encephalopathy syndrome in children with malignancies - a single-center retrospective study.

Posterior reversible encephalopathy syndrome (PRES) diagnosis relies on clinical and radiological characteristics. Clinical manifestations include focal neurologic deficits, hemiparesis, seizures with symptoms of intracranial hypertension, headache, nausea, vomiting, and visual field disturbances. The majority of patients have typical changes in magnetic resonance imaging. The epidemiology and outcomes of PRES in the pediatric cancer population have not been well described. Most of the available data are from retrospective analyses. The aim of our study was to evaluate the clinical and radiological presentation as well as the outcome of PRES in children treated for cancers in a single center. We analyzed data from 1,053 patients diagnosed with malignancies in a single center over 15 years to determine the incidence of PRES. 19/1053 (1.8%) patients developed PRES. The diagnosis was accompanied by a range of clinical symptoms including hypertension, seizures, altered mental status, and headaches. Magnetic resonance imaging was performed in all patients, and 14/19 (73.7%) exhibited typical findings consistent with PRES. Four patients (21.0%) required treatment in the Intensive Care Unit. Posterior reversible encephalopathy syndrome (PRES) is a rare but significant complication in children with cancer.There is a clear need to establish clinical criteria for PRES to improve the diagnosis and treatment of patients with PRES, particularly in the pediatric oncological population.Further studies are needed to identify the risk factors for recurrent PRES, particularly in pediatric cancer patients undergoing chemotherapy or immunosuppressive treatment.

Circulating IL-17 reduces the risk of cisplatin-induced hearing loss in children: a bidirectional two-sample Mendelian randomization study

Studies have reported that cytokines and their related signaling pathways play a role in inner ear diseases. In clinical practice, approximately 50% of pediatric cancer patients experience irreversible hearing loss after cisplatin treatment. However, currently, there is a lack of systematic research on the causal relationship between circulating cytokines and cisplatin-induced hearing loss in children. Genetic variant data for 41 circulating cytokines were obtained from a meta-analysis of genome-wide association studies (GWAS) among 8293 individuals of Finnish descent. The GWAS data for Cisplatin-induced hearing loss in children were derived from a multicenter cohort of European pediatric cancer patients and survivors (N = 390), including both cases with hearing loss after cisplatin chemotherapy and controls without hearing loss. Multiple methods were employed for bidirectional Mendelian randomization (MR) estimation. Bonferroni correction was applied to adjust the original P-values, followed by a series of sensitivity analyses. In the directional Mendelian randomization (MR) analysis, it was found that IL-17 was significantly associated with a reduced risk of Cisplatin-induced hearing loss in children (OR: 0.18, CI: 0.06–0.48, P < 0.001, FDR = 0.041). In the reverse MR analysis, there were some nominal causal relationships of Cisplatin-induced hearing loss in children with certain cytokines [M-CSF: (OR: 1.04, CI: 1.01–1.08, P = 0.010, FDR = 0.41); IL-2RA: (OR: 1.03, CI: 1.00–1.05, P = 0.044, FDR = 0.447); MIP-1β: (OR: 1.02, CI: 1.00–1.04, P = 0.041, FDR = 0.447)]. leave-one-out analysis demonstrated that only M-CSF exhibited stability. These findings reveal a causal relationship between IL-17 and cisplatin-induced hearing loss in children. Further research is needed to determine the potential protective mechanisms of IL-17 in cisplatin-induced ototoxicity.

Usefulness Of Sofosbuvir And Daclatasvir Combination In The Treatment Of HCV Infection In Childhood Cancer Patients: Experience From A Tertiary Care Hospital.

To determine the usefulness of Sofosbuvir-Daclatasvir combination in the treatment of hepatitis c virus infection in paediatric cancer.. The retrospective study was conducted at the Oncology Department of the National Institute of Child Health, Karachi, and comprised medical charts of patients who received sofosbuvir and daclatasvir from January 2018 to January 2022. Efficacy was documented by clearance of hepatitis C virus ribonucleic acid as rapid viral response, early viral response and sustained viral response at weeks 4, 12 and 24, respectively. Drug efficacy was determined by monitoring and recording adverse effects. Chemotherapy protocol for the treatment of patients concomitantly receiving direct acting antivirals was modified while looking at drug-drug interactions. The total duration of direct acting antiviral therapy was 12 weeks. Data was analysed using SPSS 24. Of the 804 patients with different malignancies, 132(16.4%) were found positive for hepatitis C virus. Of them, 28(21.21%) patients were started on direct acting antivirals; 17(60.71%) boys and 11(39.28%) girls. The overall mean age was 9.93±6.12 years. The diagnosis was pre-B acute lymphoblastic leukaemia in 18(64.28%) cases, 16 (57.14%) were on maintenance chemotherapy, and 18(64.28%) had genotype 1. Pre- and post-treatment mean alanine transaminase levels were 328.00±324.00IU and 36.00±29.00IU, respectively (p=0.003). Pre- and post- treatment mean serum bilirubin levels were 3.13±3.95mg/dl and 0.61±0.21mg/dl (p=0.022). Rapid viral response was achieved in 26(92.85%) children, while early viral response and sustained viral response were achieved in all 28(100%) patients. Minor side effects were noted in 4(14.28%) patients and chemotherapy was continued in all 28(100%) cases as per the designed protocol. The sofosbuvir-daclatasvir combination was found to be effective in hepatitis C virus treatment in paediatric cancer patients.

Pediatric precision oncology: "better three hours too soon than a minute too late".

Precision oncology is defined as the selection of an effective treatment for a cancer patient based upon genomic profiling of the patient's tumor to identify targetable alterations. The application of precision oncology toward pediatric cancer patients has moved forward more slowly than with adults but is gaining momentum. Clinical and pharmaceutical advances developed over the past decade for adult cancer indications have begun to move into pediatric oncology, expanding treatment options for young high-risk and refractory patients. As a result, the FDA has approved 23 targeted drugs for pediatric cancer indications, moving targeted drugs into the standard of care. Our precision oncology program is in a medium sized children's hospital, lacking internal sequencing capabilities and bioinformatics. We have developed methods, medical and business partnerships to provide state-of-the-art tumor characterization and targeted treatment options for our patients. We present here a streamlined and practical protocol designed to enable any oncologist to implement precision oncology options for their patients.

Long-Term Prognosis in Relation to Vitamin D Status in Pediatric Solid Tumor Patients

Background: Hypovitaminosis D is associated with oncogenesis, and the initial level of Vitamin D may play a role in determining long-term prognosis, relapse-free survival (RFS) and overall survival (OS). The purpose of our study was to follow up pediatric cancer patients for a long time in terms of their baseline Vitamin D level and disease outcomes. Methods: We collected data on the initial 25(OH)D concentration in 117 children and examined their RFS and OS using Kaplan–Meier curves. Results: The initial 25(OH)D mean value in the relapsed group was 20.35 ng/mL (SE: 2.05) and in children without relapse it was 26.14 ng/mL (SE: 1.13). Both the relapse-free and overall Kaplan–Meier curves showed a tendency for children with lower serum Vitamin D concentrations to experience cancer recurrence or fatal outcomes sooner than patients with normal serum levels. Conclusions: Our results indicated a possible correlation between higher pretreatment serum Vitamin D concentrations and improved overall and relapse-free survival.

Bloodstream Infections in Paediatric Cancer Patients with Febrile Neutropenia in a Tertiary Cancer Centre in North-East India

Background: The aim of the present study was to study the pattern of microbial flora, their susceptibility patterns, and clinical variables among bloodstream infections in febrile neutropenic patients with solid tumors and hematological malignancies in the paediatric age group in North-East India. Methods: It was a retrospective and observational study done in a single tertiary care cancer centre in North-East India. The study period was from 1st January 2020 to 31st December 2021. The study population included all the patients below the age of 18 years who developed febrile neutropenia during treatment for a diagnosed cancer. Results: A total of 378 blood culture samples were studied. Febrile neutropenia was found in 252 patients (66.7%). There were 45 positive blood cultures (17.8%) among them. Gram-negative and gram-positive organisms accounted for 62% and 38% of all positive cultures respectively. Escherichia coli (39%) was the most common gram-negative isolate, followed by Klebsiella pneumoniae (32%), Pseudomonas aeruginosa (18%) and Acinetobacter baumannii (7%). Coagulase-negative Staphylococci (CoNS) was the most common gram-positive isolate (47%). Sensitivity to beta-lactam/beta-lactamase inhibitor (BL/BLI) antibiotics like cefaperazone/sulbactam was seen in 60% of Pseudomonas isolates. Sensitivity to colistin was noted in 89% of Klebsiella and 82% of E. coli isolates. The incidence of methicillin resistant staphylococcus aureus (MRSA) was 50%. Conclusion: The knowledge of the microbiological profile and resistance patterns among patients treated for paediatric cancer with febrile neutropenia is a key factor in deciding the antimicrobial policy.

Impact of proton therapy on the DNA damage induction and repair in hematopoietic stem and progenitor cells

Proton therapy is of great interest to pediatric cancer patients because of its optimal depth dose distribution. In view of healthy tissue damage and the increased risk of secondary cancers, we investigated DNA damage induction and repair of radiosensitive hematopoietic stem and progenitor cells (HSPCs) exposed to therapeutic proton and photon irradiation due to their role in radiation-induced leukemia. Human CD34+ HSPCs were exposed to 6 MV X-rays, mid- and distal spread-out Bragg peak (SOBP) protons at doses ranging from 0.5 to 2 Gy. Persistent chromosomal damage was assessed with the micronucleus assay, while DNA damage induction and repair were analyzed with the γ-H2AX foci assay. No differences were found in induction and disappearance of γ-H2AX foci between 6 MV X-rays, mid- and distal SOBP protons at 1 Gy. A significantly higher number of micronuclei was found for distal SOBP protons compared to 6 MV X-rays and mid- SOBP protons at 0.5 and 1 Gy, while no significant differences in micronuclei were found at 2 Gy. In HSPCs, mid-SOBP protons are as damaging as conventional X-rays. Distal SOBP protons showed a higher number of micronuclei in HSPCs depending on the radiation dose, indicating possible changes of the in vivo biological response.

B - 23 The Effects of Family Functioning on Medication Adherence in Pediatric Cancer Patients.

Despite life-threatening consequences of pediatric cancer, treatment non-adherence rates range from 10-75%. Given the neurocognitive effects of chemotherapy it is important to study medication adherence to prevent disease relapse. The current study examined potential predictors of medication adherence among pediatric cancer patients. Survey data was collected from 104 parents of pediatric cancer patients through online and social media portals, family support groups, pediatric cancer websites, and foundations. Informed by the McMaster Model of Family Functioning, it was hypothesized that poor medication adherence would be predicted by multiple factors using multiple regression analysis. Results indicated poor communication (p = 0.049), behavioral control (p < 0.001), and affective responsiveness (p = 0.005) are predictors of poor medication adherence. Poor problem solving (p = 0.016) and higher degree of effort (p < 0.001) predict higher medication adherence. Post-hoc analysis indicated that when controlling for problem solving, child's sex had a significant effect on medication adherence. There was a significant effect of time since diagnosis on medication adherence after controlling for the effect of problem solving, communication, behavior control, and condition management effort. There was a significant effect of family's income on medication adherence after controlling for the effect of problem solving, communication, affective responsiveness, and condition management effort. In the current study, several predictors of adherence were identified. This knowledge helps medical and psychological professionals to work collaboratively to promote adherence. Future research is needed to further understand multicultural factors that may predict poor adherence and how specific pediatric cancer diagnoses impact family functioning.

How to manage symptoms in pediatric cancer patients enrolled in clinical trials? A review of principal patient-reported outcome screening tools

Background: In adult oncology, the practice of tracking symptoms and toxicities using patient-reported outcomes (PROs) has increased and correlates with increased survival. In contrast, symptom monitoring using PROs is not common in pediatric oncology. Only in the last couple of years attention has also been paid to the patient’s perception in pediatrics and listening to the voice of children and to making them participate in the treatment. Methods: A comprehensive literature search was conducted in MEDLINE/PubMed and PsycINFO to identify relevant articles published through December 2022. Results: From 58 non-duplicate articles, 33 met our eligibility criteria. Of these, 17 were used in clinical trials. Conclusions: The dissemination and use of these tools will therefore have surprising repercussions on the control of pain and physical symptoms of small patients as well as on physical and psychological aspects. The administration and use of the PROs ensures optimal use of the drugs currently present in clinical trials by researcher and nurse and aims at a safer and more controlled approval of new drugs.

"The place it puts us in emotionally and relationally with our child, it's damaging": understanding the real-world psychosocial needs of caregivers of childhood cancer survivors.

Understanding the lived experiences of childhood cancer caregivers can guide the development of effective psychosocial models of care. We conducted this qualitative study to understand triggers that impact the mental health, quality of life, and mental health supportive care needs of caregivers. A maximum variation sampling strategy was used to recruit study participants for semi-structured interviews. Using a grounded theory approach, transcripts were independently dual-coded using inductive thematic analysis. We conducted a secondary thematic analysis emphasizing the impact of pediatric oncology on caregiver mental health. Our findings highlight caregiver experiences connected to their child's appearance, quality of life, or change in behavior. Caregivers reported the need to transition between the role of nurturer and protector and simultaneously be part of the care team, which increased trauma for caregivers and their children. Caregivers noted that the hardest part of being a caregiver is witnessing, participating, and forcing the child to comply with cancer treatment. Caregivers were left wishing there had been more support for these situations. Our findings reveal real-world experiences that caregivers view as among the most stressful during their child's cancer journey. These events provide insight into the nuanced and most difficult experiences from the caregiver perspective in which emotional support services would be most useful. These insights will inform a future model for mental healthcare. Caregivers' treatment-related stress is associated with the quality of life of pediatric cancer patients. Supporting the mental health, quality of life, and mental health supportive care needs of childhood cancer caregivers through supportive care guidelines may positively impact the caregiver-child relationship long into survivorship.Children's and their caregivers' treatment-related stress are indelibly connected to the quality of life concerns throughout the cancer journey. Supporting the mental health, quality of life, and mental health supportive careneeds of childhood cancer caregivers through supportive care guidelines will positively impact the caregiver-child relationship long into survivorship.

Distinct clinical phenotypes in paediatric cancer patients with sepsis are associated with different outcomes—an international multicentre retrospective study

Identifying phenotypes in sepsis patients may enable precision medicine approaches. However, the generalisability of these phenotypes to specific patient populations is unclear. Given that paediatric cancer patients with sepsis have different host response and pathogen profiles and higher mortality rates when compared to non-cancer patients, we determined whether unique, reproducible, and clinically-relevant sepsis phenotypes exist in this specific patient population. We studied patients with underlying malignancies admitted with sepsis to one of 25 paediatric intensive care units (PICUs) participating in two large, multi-centre, observational cohorts from the European SCOTER study (n=383 patients; study period between January 1, 2018 and January 1, 2020) and the U.S. Novel Data-Driven Sepsis Phenotypes in Children study (n=1898 patients; study period between January 1, 2012 and January 1, 2018). We independently used latent class analysis (LCA) in both cohorts to identify phenotypes using demographic, clinical, and laboratory data from the first 24h of PICU admission. We then tested the association of the phenotypes with clinical outcomes in both cohorts. LCA identified two distinct phenotypes that were comparable across both cohorts. Phenotype 1 was characterised by lower serum bicarbonate and albumin, markedly increased lactate and hepatic, renal, and coagulation abnormalities when compared to phenotype 2. Patients with phenotype 1 had a higher 90-day mortality (European cohort 29.2% versus 13.4%, U.S. cohort 27.3% versus 11.4%, p<0.001) and received more vasopressor and renal replacement therapy than patients with phenotype 2. After adjusting for severity of organ dysfunction, haematological cancer, prior stem cell transplantation and age, phenotype 1 was associated with an adjusted OR of death at 90-day of 1.9 (1.04-3.34) in the European cohort and 1.6 (1.2-2.2) in the U.S. cohort. We identified two clinically-relevant sepsis phenotypes in paediatric cancer patients that are reproducible across two international, multicentre cohorts with prognostic implications. These results may guide further research regarding therapeutic approaches for these specific phenotypes. Part of this study is funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development.

Delivery of re-irradiation and complex palliative radiotherapy using proton therapy in pediatric cancer patients.

The intent of this study is to characterize indications for pediatric palliative-intent proton radiation therapy (PIPRT). We retrospectively reviewed patients 21years and younger who received PIPRT. We defined PIPRT as radiotherapy (RT) aimed to improve cancer-related symptoms/provide durable local control in the non-curative setting. Mixed proton/photon plans were included. Adjacent re-irradiation (reRT) was defined as a reRT volume within the incidental dose cloud of a prior RT target, whereas direct reRT was defined as in-field overlap with prior RT target. Acute toxicity during RT until first inspection visit was graded according to the Common Terminology Criteria for Adverse Events. The Kaplan-Meier method, measured from last PIPRT fraction, was used to assess progression-free survival (PFS) and overall survival (OS). Eighteen patients underwent PIPRT between 2014 and 2020. Median age at treatment start was 10years [2-21]. Median follow-up was 8.2months [0-48]. Treatment sites included: brain/spine [10], abdomen/pelvis [3], thorax [3], and head/neck [2]. Indications for palliation included: durable tumor control [18], neurologic symptoms [4], pain [3], airway compromise [2], and great vessel compression [1]. Indications for protons included: reRT [15] (three adjacent, 12 direct), craniospinal irradiation [4], reduction of dose to normal tissues [3]. Sixteen experienced grade (G) 1-2 toxicity; two G3. There were no reports of radionecrosis. Median PFS was 5.3months [95% confidence interval (CI): 2.7-16.3]. Median OS was 8.3months [95% CI: 5.5-26.3]. The most common indication for PIPRT was reRT to provide durable tumor control. PIPRT appears to be safe, with no cases of high-grade toxicity.

Vitamin D Status in Children With High-risk Neuroblastoma.

Vitamin D deficiency has become a matter of concern in pediatric cancer patients. A relationship between neuroblastoma and Vitamin D signaling pathways has been revealed with interest in the antiproliferative and antiinvasive properties of vitamin D. Our aim is to describe the prevalence of Vitamin D deficiency among children with high-risk neuroblastoma (HR-NB) and to explore its association with disease status. In all, 182 patients with HR-NB were managed at our center from 2017 to 2021. Serum 25(OH)D levels were tested at the first blood analysis performed and correlated with clinical data and disease status. One hundred forty-eight (81.4%) had low 25(OH)D levels (48.4% categorized as deficiency (25(OH)D below 20ng/mL) and 33.0% as insufficiency (25(OH)D 20 to 30ng/mL). Median Vitamin D level was 20.2ng/mL. Vitamin D levels were not associated with race or sex. Although malnourished patients had lower median 25(OH)D levels(11.1ng/mL), no statistical association was observed with Vitamin D deficiency. There was no association between Vitamin D levels and disease status. An inverse correlation was found between age and vitamin D levels ( P =0.0040). A concerning high prevalence of low Vitamin D levels affects more than two-thirds of patients with HR-NB in our cohort, regardless of the disease status at the time of evaluation. Older children are at a higher risk for deficient levels of vitamin D.

PB0921 Patients with Non-CVC Symptomatic Venous Thrombotic Events Have Significantly Inferior Survival Outcomes in Pediatric Cancer Patients: A Population-Based Study

PB0921 Patients with Non-CVC Symptomatic Venous Thrombotic Events Have Significantly Inferior Survival Outcomes in Pediatric Cancer Patients: A Population-Based Study

PB0979 Significantly Increased CVC Replacement in Patients with Both Symptomatic and Incidental Venous Thrombotic Events in Pediatric Cancer Patients: A Population-Based Study

PB0979 Significantly Increased CVC Replacement in Patients with Both Symptomatic and Incidental Venous Thrombotic Events in Pediatric Cancer Patients: A Population-Based Study

Quality of life in parents of Turkish and Syrian pediatric bone marrow transplant and oncology patients.

The success of the treatment depends on the well-being of the parents in pediatric cancer patients. In addition, migrants need to deal with the consequences of war. Our purpose was to compare the HRQoL of parents of Syrian and Turkish children followed in our bone marrow transplant and oncology units. One hundred SF 36 questionnaires, fifty from each group were collected between October 2019 and March 2020 in this cross-sectional study. Demographic characteristics of the patients (sex, age, cancer type, presence of relapse, duration of follow-up) and education level of parents were recorded. Analyses were performed using IBM SPSS Statistics version 20.0. Turkish parents reported better results in physical functioning, emotional well-being, physical pain, general health, and physical health composite score (P < 0.05). There were more fathers in the Syrian group and education status was significant between the two groups (P = 0.01, P = 0.001, respectively). There was no correlation between QoL and education levels in the Turkish group. In Syrian parents, pain score was high in middle school graduates (P = 0.043). In the presence of relapse, although the physical function score decreased, the physical role function score increased in Turkish parents (P = 0.0035, P = 0.005, respectively). Syrian parents' emotional role function and energy/fatigue score were both increased when children had relapses (P = 0.027for both). Migration is a complex issue. Turkish parents were better in physical functioning, emotional well-being, physical pain, general health, and physical health composite score. Screening for parental burden, assisting them to find appropriate support services is essential in improving the health and QoL of both our patients and their parents.

Optical genome mapping identifies structural variants in potentially new cancer predisposition candidate genes in pediatric cancer patients.

Genetic predisposition is one of the major risk factors for pediatric cancer, with ~10% of children being carriers of a predisposing germline alteration. It is likely that this is the tip of the iceberg and many children are underdiagnosed, as most of the analysis focuses on single or short nucleotide variants, not considering the full spectrum of DNA alterations. Hence, we applied optical genome mapping (OGM) to our cohort of 34 pediatric cancer patients to perform an unbiased germline screening and analyze the frequency of structural variants (SVs) and their impact on cancer predisposition. All children were clinically highly suspicious for germline alterations (concomitant conditions or congenital anomalies, positive family cancer history, particular cancer type, synchronous or metachronous tumors), but whole exome sequencing (WES) had failed to detect pathogenic variants in cancer predisposing genes. OGM detected a median of 49 rare SVs (range 27-149) per patient. By analysis of 18 patient-parent trios, we identified three de novo SVs. Moreover, we discovered a likely pathogenic deletion of exon 3 in the known cancer predisposition gene BRCA2, and identified a duplication in RPA1, which might represent a new cancer predisposition gene. We conclude that optical genome mapping is a suitable tool for detecting potentially predisposing SVs in addition to WES in pediatric cancer patients.

The Characteristics and Follow-Up of SARS-CoV-2 Infection in Pediatric Oncology Patients.

Introduction Clinical data about the first and second most prominent waves of SARS-CoV-2 among pediatric cancer patients were inconsistent. This study aims to retrospectively report the clinical characteristics and outcomes of SARS-CoV-2 infection in pediatric oncology patients. Methods This is an observational, retrospective study conducted in a tertiary care oncology center from March 2020 to May 2022. We reviewed the prevalence, severity of symptoms, and duration of positivity in relation to blood count laboratory data and mortality with a follow-up of 30 days post-infection for SARS-CoV-2. Results A total of 396 PCR tests were performed on 342 pediatric cancer patients. The overall rate of SARS-CoV-2 positivity was 43.1% (2.7% in the first wave and 95.4% in the second wave). Among 342 screened pediatric cancer patients, 72 patients had confirmed SARS-CoV-2 positivity in 92 different episodes. Nearly 59% had a mild or moderate infection, with fever and cough as the predominant presentations. The mean duration of positivity was 18.4±7.76 days. Comparing the laboratory values before and after acquiring the COVID-19 infection, only monocytes, hemoglobin, hematocrit, and platelets were statistically significantly affected, with P-values of 0.002, 0.03, 0.02, and 0.01, respectively. More than 18% of patients had grade 3 to 4 neutropenia (absolute neutrophil count=0.39±0.35) before COVID-19 infection and remained neutropenic throughout the disease, regardless of symptom severity. The mean recovery time was 13.67±8 days, which resulted in a delay in cancer treatment delivery of up to four weeks in 42.2% of patients. Conclusion Our data demonstrated that pediatric cancer patients with SARS-CoV-2 infection have a mild to moderate course of COVID-19 disease, with the majority being symptomatic, yet a great portion of our study population experienced treatment interruptions reaching up to four weeks caused by COVID-19.