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Objective: The management of central venous catheter (CVC) occlusion remains an area without clear evidence-based guidelines. Studies have been conducted that compare the use of heparin and normal saline for reducing thrombosis, but the evidence is not strong enough to suggest a significant advantage of one over the other. Therefore, the study aimed to assess the effectiveness of heparin and normal saline flushing in preventing CVC occlusion in pediatric patients with cancer. Data Sources: A comprehensive search was conducted in PubMed, Web of Science, Cochrane, MEDLINE, CINAHL, Embase, World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov platform using specific keywords. The search was conducted until March 2022. Five randomized controlled trials are included in this study. Conclusion: Five studies with a total of 316 pediatric cancer patients met the inclusion criteria. The studies were found to be heterogeneous due to variations in the types of cancer, heparin concentration, flushing frequency of CVCs, and methods used to measure occlusion. Despite these differences, there was no significant difference in the effect of flushing with heparin and normal saline in preventing CVC occlusion. The analysis revealed that normal saline is as effective as heparin in preventing CVC occlusion among pediatric cancer patients. Implications for Nursing Practice: This systematic review and meta-analysis demonstrated that there is no significant difference between the use of heparin and normal saline flushing in preventing CVC occlusion among pediatric cancer patients. Considering the potential risks of heparin, the use of normal saline flushing may be recommended to prevent CVC obstruction.

PURPOSE Constitutional mismatch repair deficiency syndrome (CMMRD) is a lethal cancer predisposition syndrome characterized by early-onset synchronous and metachronous multiorgan tumors. We designed a surveillance protocol for early tumor detection in these individuals. PATIENTS AND METHODS Data were collected from patients with confirmed CMMRD who were registered in the International Replication Repair Deficiency Consortium. Tumor spectrum, efficacy of the surveillance protocol, and malignant transformation of low-grade lesions were examined for the entire cohort. Survival outcomes were analyzed for patients followed prospectively from the time of surveillance implementation. RESULTS A total of 193 malignant tumors in 110 patients were identified. Median age of first cancer diagnosis was 9.2 years (range: 1.7-39.5 years). For patients undergoing surveillance, all GI and other solid tumors, and 75% of brain cancers were detected asymptomatically. By contrast, only 16% of hematologic malignancies were detected asymptomatically ( P < .001). Eighty-nine patients were followed prospectively and used for survival analysis. Five-year overall survival (OS) was 90% (95% CI, 78.6 to 100) and 50% (95% CI, 39.2 to 63.7) when cancer was detected asymptomatically and symptomatically, respectively ( P = .001). Patient outcome measured by adherence to the surveillance protocol revealed 4-year OS of 79% (95% CI, 54.8 to 90.9) for patients undergoing full surveillance, 55% (95% CI, 28.5 to 74.5) for partial surveillance, and 15% (95% CI, 5.2 to 28.8) for those not under surveillance ( P < .0001). Of the 64 low-grade tumors detected, the cumulative likelihood of transformation from low-to high-grade was 81% for GI cancers within 8 years and 100% for gliomas in 6 years. CONCLUSION Surveillance and early cancer detection are associated with improved OS for individuals with CMMRD.

The purpose of this study was to describe factors affecting the place of death of children with cancer at the end of life.The descriptive phenomenological approach was used. Eighteen mothers who lost their children to cancer participated in in-depth interviews. Data were analysed using MAXQDA software version. Codes and categories were developed inductively from participants' narratives.The factors affecting the place of death of children were categorised into two main themes: (1) desires and (2) conditions. Most of the mothers reported that their deceased children wanted to be with their families at the end of life and they wanted to go home. The conditions related to health services were defined as the barriers to the death of their children in the places of death preferred by the mothers.The desire to be close to the child was the main factor affecting the parents' decisions. The findings revealed the prevailing circumstances in the death place decision beyond parental desires. These were the child's health conditions, physical conditions of hospitals, and the lack of home care and paediatric palliative care services, which were factors related to the system, and the lack of other options for parents.

OBJECTIVE To investigate the variant spectrum and genotype-phenotype correlations in a Turkish cohort with Neurofibromatosis Type-1 (NF1). MATERIALS AND METHODS We retrospectively investigated the clinical and molecular data of 138 NF1 patients from 129 families who had been followed-up for a median of 3.9 (1.25-18.5) years. RESULTS NF1 sequencing revealed 73 different intragenic variants, 19 of which were novel. Seven large deletions were detected by multiplex ligation-dependent probe amplification (MLPA) analyses. The total detection rate of pathogenic NF1 variants was found to be 87.1%. Comparing age groups, cutaneous neurofibromas, freckling, and Lisch nodules were more prevalent in patients older than 12 years (p > .05). Optic glioma detected in 17.3% of the patients and was significantly more common before the age of 6 (p > .001). Other solid tumors developed in 5% of the patients. There was no genotype-phenotype correlation between patients with truncating and nontruncating variants. However, six out of seven patients with large deletions had significant developmental delay, one patient with the c.2970_2972delAAT (p.Met992del) variant had only typical pigmentary features, and another patient with the c.4267A > G (p.Lys1423Glu) variant had CALMs, freckling, neurofibromas, and Noonan-like phenotype. CONCLUSIONS We described 19 novel variants and seven large deletions in NF1. Applying MLPA assay in NF1 is useful in expanding the molecular diagnosis. Although very limited genotype-phenotype correlation has been reported in NF1, the fact that specific phenotypic findings were observed in our patients with large deletions and two intragenic variants supports the studies published recently.

Patients with childhood, adolescent, and young adult cancer who will be treated with gonadotoxic therapies are at increased risk for infertility. Many patients and their families desire biological children but effective communication about treatment-related infertility risk and procedures for fertility preservation does not always happen. The PanCareLIFE Consortium and the International Late Effects of Childhood Cancer Guideline Harmonization Group reviewed the literature and developed a clinical practice guideline that provides recommendations for ongoing communication methods for fertility preservation for patients who were diagnosed with childhood, adolescent, and young adult cancer at age 25 years or younger and their families. Moreover, the guideline panel formulated considerations of the ethical implications that are associated with these procedures. Grading of Recommendations Assessment, Development and Evaluation methodology was used to grade the evidence and recommendations. In this clinical practice guideline, existing evidence and international expertise are combined to develop transparent recommendations that are easy to use to facilitate ongoing communication between health-care providers and patients with childhood, adolescent, and young adult cancer who might be at high risk for fertility impairment and their families.

Background: Cancer incidence in the world is predicted to increase in the next decade. While progress has been in diagnosis and treatment, much still remains to be done to improve cancer pain therapy, mainly in underserved communities in low-income countries. Objective: To determine knowledge, beliefs, and barriers regarding pain management in both high- and low-income countries (according to the WHO classification); and to learn about ways to improve the current state of affairs. Design: Descriptive survey. Setting/Subjects: Fifty-six countries worldwide; convenience sample of 1639 consisted of 36.8% physicians; 45.1% nurses, and 4.5% pharmacists employed in varied settings. Results: Improved pain management services are key elements. Top barriers include religion factors, lack of appropriate education and training at all levels, nonadherence to guidelines, patients' reluctance to report on pains, over regulation associated with prescribing and access to opioid analgesics, fear of addiction to opioids, and lack of discussions around prognosis and treatment planning. Conclusion: The majority of patients with cancer in low-income countries are undertreated for their pain. Promoting cancer pain accredited program of training and education on pain management for physicians and nurses is crucial, as well as advocating policymakers and the public at large. Keywords: cancer; global; management; opioids; pain.

The aim of the study was to investigate the frequency and types of mutations on the RB1 gene at the familial, clinical, and ethnic levels which are known to have an important role in the genetics of retinoblastoma in Turkish population. RB1 gene mutation analysis was performed in 219 people (122 probands, 14 family members with retinoblastoma and 83 clinically healthy family members) in total. All 27 exons and close intronic regions of the RB1 gene were sequenced for small deletions and insertions using both the Sanger sequencing or NGS methods, and also the large deletions and duplications were investigated by both the Multiplex Ligation Probe Amplification (MLPA) analysis and the Copy Number Variation (CNV) algorithm. The general RB1 gene mutation frequency of the patients with retinoblastoma was 41.9%. The bilateral retinoblastoma rate was 34.5% in our study population. It was striking that approximately 51.5% of our patients were diagnosed 12 months earlier, and de novo mutation occurred in 90.4% of the patients. Small genetic rearrangement mutations were detected in 78.9% of patients and Large Genetic Rearrangement (LGR) was detected in 21.1% of patients. There was a relationship between the eye color of the RB patients and RB1 mutations. As a conclusion, the familial, clinical and ethnical level of the RB1 gene mutations which are known to have a significant role in genetics of retinoblastoma were investigated, and different RB1 mutations, 10 of which are novel, have been identified on the RB1 gene sequence.

Survival rates for pediatric cancer have improved significantly over the past few decades. However, the journey from diagnosis to treatment and then follow-up is challenging. Families of children with cancer struggle with an acute life-altering disease as well as with long-term possible chronic complications. In most types of pediatric cancer, the duration of the treatment is long and both the child and caregivers may spend many months in the hospital, which affects the child, their entire family, and those close to the child. The care of a child with cancer must be family-centered, and it is essential to understand the cultural background of the family. Cultural differences should be respected throughout all interactions—while informing the patient and family of the diagnosis, during treatment, and at the end of life. Psychosocial support must be provided to the child, family, and health care staff. Palliative care (PC) is a set of approaches that aims to improve the physical, social, and psychological well-being of both the patient and the family. PC should begin at diagnosis and continue throughout treatment until the end of life. Health care professionals should be sensitive to and tolerant of various traditions or religious beliefs in order to meet the needs of patients and families.

Bilateral testicular tumors are very rare in pediatric patients and only a few case reports have been reported. These patients have a high risk of sterility due to bilateral orchiectomy and subsequent gonadotoxic treatments. Therefore, if possible, testis-sparing surgery should be performed in patients with benign masses and testicular tissue preservation may be recommended in order to maintain fertility in later life. We present a 23 months old boy with synchronous bilateral testicular tumor managed with unilateral orchiectomy and testis-sparing surgery and testicular tissue cryopreservation performed to the controlateral side. We also review the literature on bilateral testis tumors in children.

Pineoblastomas (PB) are rare tumors of the central nervous system and are more common in children. There is no consensus about standard of care. The objective of this study is to analyze the outcome of children with PB.Six patients with PB who were diagnosed between 1990-2012 were evaluated retrospectively. Demographics, age of diagnosis, first complaint, tumor region, diagnosis type, seeding metastasis to the spinal axis or cerebrospinal fluid (CSF), treatment and survival of these patients were recorded.Three patients had subtotal resection and all patients received chemotherapy and craniospinal irradiation (CSI) after diagnosis. Median follow-up after treatment was 5.5 (range:1-19) years. Two patients are alive with no evidence of disease for 7.5 and 10 years, one of whom was diagnosed with papillary thyroid carcinoma 9.5 years after treatment. One of the patients who died had lived for 19 years after diagnosis.Pineoblastomas are rare but very aggressive tumors; more effective treatment strategies are needed. Survivors should be followed up for late effects such as second malignancies and endocrine deficiencies.

IntroductionChildhood cancer is a leading cause of death. It is unclear whether the COVID-19 pandemic has impacted childhood cancer mortality. In this study, we aimed to establish all-cause mortality rates for childhood cancers during the COVID-19 pandemic and determine the factors associated with mortality.MethodsProspective cohort study in 109 institutions in 41 countries. Inclusion criteria: children ResultsAll-cause mortality was 3.4% (n=71/2084) at 30-day follow-up, 5.7% (n=113/1969) at 90-day follow-up and 13.0% (n=206/1581) at 12-month follow-up. The median time from diagnosis to multidisciplinary team (MDT) plan was longest in low-income countries (7 days, IQR 3–11). Multivariable analysis revealed several factors associated with 12-month mortality, including low-income (OR 6.99 (95% CI 2.49 to 19.68); pConclusionsChildren with cancer are more likely to die within 30 days if infected with SARS-CoV-2. However, timely treatment reduced odds of death. This report provides crucial information to balance the benefits of providing anticancer therapy against the risks of SARS-CoV-2 infection in children with cancer.

Introduction Standards for chemotherapy against choroid plexus tumors (CPT) have not yet been established. Methods CPT-SIOP-2000 (NCT00500890) was an international registry for all CPT nesting a chemotherapy randomization for high-risk CPT with Carboplatin/Etoposide/Vincristine (CarbEV) versus Cyclophosphamide/Etoposide/Vincristine (CycEV). Patients older than three years were recommended to receive irradiation: focal fields for non-metastatic CPC, incompletely resected atypical choroid plexus papilloma (APP) or metastatic choroid plexus papilloma (CPP); craniospinal fields for metastatic CPC/APP and non-responsive CPC. High risk was defined as choroid plexus carcinoma (CPC), incompletely resected APP, and all metastatic CPT. From 2000 until 2010, 158 CPT patients from 23 countries were enrolled. Results For randomized CPC, the 5/10 year progression free survival (PFS) of patients on CarbEV (n = 20) were 62%/47%, respectively, compared to 27%/18%, on CycEV (n = 15), (intention-to-treat, HR 2.6, p = 0.032). Within the registry, histological grading was the most influential prognostic factor: for CPP (n = 55) the 5/10 year overall survival (OS) and the event free survival (EFS) probabilities were 100%/97% and 92%/92%, respectively; for APP (n = 49) 96%/96% and 76%/76%, respectively; and for CPC (n = 54) 65%/51% and 41%/39%, respectively. Without irradiation, 12 out of 33 patients with CPC younger than three years were alive for a median of 8.52 years. Extent of surgery and metastases were not independent prognosticators. Conclusions Chemotherapy for Choroid Plexus Carcinoma is feasible and effective. CarbEV is superior to CycEV. A subset of CPC can be cured without irradiation.

The life span of patients with primary and secondary immunodeficiencies has increased due to recent advances in diagnostic and therapeutic strategies. Primary immune deficiencies (PIDs) are genetic disorders that predispose patients to frequent infections, autoimmunity and malignancies. Genomic instability due to defective DNA repair processes and other unknown mechanisms in patients with PID leads to an enhanced risk of cancer. PIDs were originally described as rare diseases occurring only in infants and young children, which are associated with severe clinical symptoms. However, advances in gene sequencing technologies, have revealed that they are much more common than originally appreciated and are present in older children, adolescents, and adults. After infection, malignancy is the most prevalent cause of death in both children and adults with PIDs. The overall risk of developing cancer in patients with PID is estimated to range from 4.7 to 5.7 percent. A 1.4 to 1.6-fold excess relative risk of cancer has been reported for PIDs. Increasing awareness among physicians regarding PID and cancer may lead to earlier diagnosis which may decrease morbidity and mortality. In this paper, we review the various categories of PIDs in children and highlight their association with various malignancies. MEDLINE was searched to identify articles for inclusion. Three authors have independently screened literature search results from MEDLINE and abstracted data from studies dealing with cancers of children among primary immune deficiencies.

BACKGROUND: Gliomatosis cerebri (GC), a radiologically defined diffusely infiltrating glioma, is no longer considered a distinct entity since the 2016 WHO classification for tumors of the CNS. Due to its rarity and dismal prognosis treatment recommendations in children remain ambiguous. Using central neuroradiological review, we performed a multi-institutional, retrospective study of GC providing comprehensive radiological, clinical, and (epi)genetic characterization. RESULTS: We included 104 patients between 1-19 years. Within a median follow-up of 15.5 months (range, 2.3-138.8), 93 patients (89.4 %) had died, 4 (3.8 %) were lost to follow-up and 7 (6.8 %) were alive with stable/progressive disease. Median progression-free- (PFS) and overall survival (OS) were 8.6 months (interquartile range, 4.3-14.0) and 15.5 months (10.9-27.7), respectively. Former WHO grading correlated significantly with median OS: WHO °II: 47.8 months (25.2-55.7); WHO °III: 15.9 months (11.4-26.3); WHO °IV: 10.4 months (8.8-14.4) (p

Objectives The aim of the study was to evaluate the long-term outcome and late effects in pediatric patients with nasopharyngeal carcinoma (NPC) treated with neoadjuvant chemotherapy (NACT), followed by radiotherapy (RT). Methods Ninety-two children (65 male, 27 female) diagnosed with NPC between 1989 and 2017 in the Istanbul University, Institute of Oncology were evaluated retrospectively. NACT consisted of three cycles of cisplatin-containing regimen every 3 weeks, followed by RT. Results The median age was 13 years (5-18 years). Most had locoregionally advanced disease (stage III/IVA/IVB) and five had distant metastases at presentation. At a median follow-up of 108 months (3-332 months), 5- and 10-year overall survival rates and event-free survival rates were 87.5%, 79.7% and 82.1%, 78.9%, respectively. Three patients with distant metastasis are long-term survivors. Thirteen patients relapsed at a median of 8 months (2-23 months). Hypothyroidism (36%) and xerostomia (25%) were the most frequent long-term treatment-related toxicities. Nine second malignancies developed in eight patients, eight in the irradiated field at a median of 14 years (range 5-26 years), five of whom are long-term survivors after curative surgery. Conclusions Three courses of cisplatin-containing NACT, followed by RT lead to high survival and locoregional control rate in advanced stage NPC in children. Patients with distant metastasis should also be treated with curative intent by systemic chemotherapy and locoregional radiotherapy. Patients should be followed closely for recurrences and long-term morbidities including second malignancies, which may be treated with curative surgeries if diagnosed early.

Medulloblastoma is one of the most common malignant brain tumors in the pediatric population. Recent studies identified four distinct medulloblastoma subgroups with different molecular alterations and pathways, and natural courses and outcomes. To evaluate the results of surgical and medical treatments of patients with medulloblastoma and compare them among the medulloblastoma subgroups. The clinical and radiological features, medical and surgical management and treatment outcomes and their correlation with molecular subgroups of 58 patients treated for medulloblastoma in the last 20 years were evaluated. Fifty-eight patients, of whom 35 were male and 23 were female, were evaluated. The median age was 6 years (range, 1–19 years). The most common symptoms were nausea and vomiting (60%). Forty-three percent of the patients had headache and 40% had ataxia. Previous pathology reports revealed that 43 (74%), eight (14%), five (8%), and two (3%) had classic, desmoplastic, desmoplastic/nodular, and anaplastic morphologies, respectively. After the subgroup analyses, five patients (12%) were attributed to the wingless subgroup (WNT) group; 14 (32.5%), to the sonic hedgehog subgroup (SHH) group; and 24 (56%), to the non-WNT non-SHH group. On the basis of immunohistochemical analysis results, 15 patients could not be attributed to any subgroups. The clinical risk groups (average vs high-risk) and age at diagnosis (≥ 3 years vs

Pleuropulmonary blastoma (PPB) is a potentially aggressive, rare childhood neoplasia. We investigated histopathological features, survival, and DICER1 hotspot mutations among PPB patients. Archive records at our institution were reviewed, covering a 20-year period. Thirteen children (6 males and 7 females) with a mean age of 30.5 (range 6–83) months were included. The tumor subtypes were type I in 6 (46%), type II in 4 (31%), and type III in 3 (23%). Only tumors with type II and type III histology showed anaplasia (4/7, 57%). Median follow-up was 28 (range 9–216) months. Three-year overall survival rate was 83.3% and 3-year progression-free survival rate was 25%. Progression was seen in 60% (3/5) of type I and 66.7% (4/6) of type II and type III cases. Two patients died of disseminated disease at 9 and 44 months. Hotspot missense mutations on DICER1 gene were detected in all 11 patients with available tumor tissue. We found an additional novel germline loss-of-function mutation (c.5436dupT; p.E1813*) in 1 case. To the best of our knowledge, this is the first study to investigate hotspot missense mutations on DICER1 gene among the largest series of Turkish children with PPB.

B-cell lymphoblastic lymphoma (BCP-LBL) and B-cell acute lymphoblastic leukemia (BCP-ALL) are the malignant counterparts of immature B-cells. BCP-ALL is the most common hematological malignancy in childhood, while BCP-LBL accounts for only 1% of all hematological malignancies in children. Therefore, BCP-ALL has been well studied and treatment protocols have changed over the last decades, whereas treatment for BCP-LBL has stayed roughly the same. Clinical characteristics of 364 pediatric patients with precursor B-cell malignancies were studied, consisting of BCP-LBL (n = 210) and BCP-ALL (n = 154) patients. Our results indicate that based on the clinical presentation of disease, B-cell malignancies probably represent a spectrum ranging from complete isolated medullary disease to apparent complete extramedullary disease. Hepatosplenomegaly and peripheral blood involvement are the most important discriminators, as both seen in 80% and 95% of the BCP-ALL patients and in 2% of the BCP-LBL patients, respectively. In addition, we show that the overall survival rates in this cohort differ significantly between BCP-LBL and BCP-ALL patients aged 1–18 years (p = 0.0080), and that the outcome for infants (0–1 years) with BCP-LBL is significantly decreased compared to BCP-LBL patients of all other pediatric ages (p < 0.0001).

e22016 Background: Optic pathway gliomas (OPG) constitute 1-5% of childhood brain tumors. The presence of neurofibromatosis type 1 (NF-1) is generally associated with more indolent disease. The aim of this study is to evaluate patients with optic pathway gliomas diagnosed/treated/ followed in a single center over 32 years. Methods: The medical files of 85 patients with OPG diagnosed/treated between 1990-2021 in the Istanbul University, Oncology Institute were retrospectively assessed for demographic, clinical characteristics, treatment and outcome. Results: The median age of the 85 patients (42 male, 43 female) was 60 (1-216) months, 53 (62.4%) had NF-1. Seven had diencephalic syndrome (8.2%). According to Dodge classification, 23 (27.1%) had Dodge 1, 30 (35.3%) Dodge 2 and 32 (37.6%) Dodge 3 disease. Median follow up time was 10.5 years (1-31 years). Twenty (23.5%) patients had stable disease and were followed without treatment, 14 patients underwent surgery (5 gross total tumor resection, 2 subtotal resection, 3 ventriculoperitoneal shunt operation, 4 excision/biopsy). 7 patients recieved radiotherapy (RT), none had NF1. 56 patients received chemotherapy (CT) due to severe/progressive clinical symptoms (such as diencephalic syndrome, visual impairment, nystagmus) or radiologic progressive disease. Chemotherapy consisted of an adapted SIOP-LGG regimen: vincristine (VCR) 1.5 mg/m²/dose and carboplatinum 550 mg/m²/dose every 21 days for three courses with weekly VCR, followed by VCR and carboplatinum every 28 days for a total of 12 cycles (3 cycles induction, 9 cycles consolidation). Vinblastin or cisplatinum with etoposide were used for second line or further treatment in progressive disease. One of the seven patients who had diencephalic syndrome and two of the 3 patients with leptomeningeal metastasis died. Ocular findings were recorded in 47 patients: vision was stable in 30 (63.8%), improved in 15 (31.9%), detoriated in 2 (4.3%). Radiology (MRI) revealed stable disease/regression of tumor in 41 patients, and complete regression of spinal metastasis in 1 patient. Endocrinologic follow-up was done and 13(15.2%) recieved hormonal treatment. Ten year overall survival(S) in all patients, in patients with NF1 and without NF1 were 96.5%, 96.1% and 95%, respectively; 10 year event free survival (EFS) in all patients, in patients with NF1 and without NF1 were 80.6%, 90.5% and 60% (p:0.001) respectively. Conclusions: OPG may remain indolent for many years after diagnosis, especially in patients with NF 1. However, these tumors develop progressive characteristics and can cause visual disturbances, endocrine dysfunction, blindness and even death among some of the patients. In young children who are symptomatic/have progressive disease, chemotherapy with an adapted regimen consisting of vincristine and carboplatinum seems to be effective and provides a relatively good quality of life.

e22007 Background: Retinoblastoma (RB) is the most common intraocular malignancy in children, caused by mutations in the tumor suppressor RB1 gene. Patients with bilateral/trilateral/familial RB are considered to have hereditary RB (1 germline, 1 somatic mutation); although most unilateral RB are nonhereditary (2 somatic mutations), some have germline RB1 mutation. Identification of RB1 mutations and genetic counseling is essential to assess the risk of developing RB in the patients´ relatives and to prevent the disease. The aim of this study is to assess the frequency/type of RB1 gene mutations in a large cohort of Turkish RB cases. Methods: RB1 gene mutation screening was performed in peripheral blood samples of 219 individuals (122 children with RB/14 family members with RB/83 healthy family members of 47 probands with RB1 mutations) followed in the Istanbul University, Oncology Institute. All 27 exons and close intronic regions of the RB1 gene were sequenced for small deletions and insertions using the Sanger sequencing (2013-2018) or Next Generation Sequencing (2019-2021); large deletions and duplications were investigated both by Multiplex Ligation Probe Amplification (MLPA) and copy number variation (CNV). Correlation with demographic and clinical data were evaluated. Results: After RB1 mutation screening, mutations were detected in 57 (41.9%) of 136 patients. RB1 mutations was observed in 23/84 (27.4%) patients with unilateral RB, in 30/47 (63.8%) bilateral RB, in 3/3 trilateral RB, and1/2 unilateral retinoma. Of these mutations, 45 (78.9%) were small genetic rearrangements and 12 (21.1%) large genetic rearrangements. Frameshift mutations were found in 11, nonsense in 18, splice error in 11, and missense mutation in 1, synonymous substitution in 2, upstream substitution in 2 patients. Ten novel mutations were found. Three of 83 healthy family members also had germline RB1 mutation. The disease was hereditary in 13 (22.8%); and de novo (77.2 %) in 44 of the 57 patients with mutations. Three siblings were found to have RB1 mutation, while their parents did not. Patients diagnosed as infants (RB1 mutation found in 63.2% of 70 infants vs in 36.8% of older ones, p:0.021); those with bilateral/trilateral RB (66 vs 27.4%, p:0.0001); those with light (green-blue) iris color vs dark color (71.4% vs 36.5%. p:0.003) had higher frequency of RB1 gene mutation. There was no significant correlation regarding gender or ICRB stage and RB1 mutation frequency. Conclusions: RB1 gene mutation was found in 41.9% of Turkish children with RB, in 63.8% of bilateral and 27.4% of unilateral RB. 10 novel mutations of the RB1 gene were found according to the Leiden Open Variation Database and the Human Gene Mutation Database.The mutation frequency was significantly higher in patients with bilateral/trilateral RB, in infants, in those with light iris color. In bilateral RB with no RB1 mutation, other genes/RB1 gene methylation and expression status may play a role in the pathogenesis.

WOS:000614296900001 PMID: 33538100 Adults with cancer are reported to have a higher risk for coronavirus disease (COVID-19) infection and more severe disease and mortality than the general population.1,2 Although children seem to be at a lower risk for COVID-19 than adults,3–5 data specifically addressing children with cancer are limited

Palliative Care (PC) is defined by the World Health Organization (WHO) as a support provided by multiple disciplines in order to improve the quality of life of both patients and their caregivers, throughout the disease course, from diagnosis to end-of-life. PC aims to prevent and treat symptoms and side effects of the disease and its treatment. PC is well developed in most high- -income countries; however in most low-income settings, where approximately 80% of patients with cancer requiring PC care for advanced disease live, PC services are still uncommon. Health indicators monitoring global PC development are policy, education, use of medicines, service provision and professional activity. Globally, PC development may be categorized as Group 1 (no known hospice-PC activity), Group 2 (capacity-building activity), Groups 3a Isolated PC provided, 3b Generalized PC provided, 4a hospice-PC services at a stage of integration into regular service provision, and 4b hospice-PC services at a stage of advanced integration into regular service provision. Spirituality is an essential element of patient-centered PC. The use of Complementary and Traditional Medicine (CTM) in Middle Eastern countries is widespread. There are wide discrepancies in cancer care and PC in many regions of the world. The Individualized Care Planning and Coordination (ICPC) Model is designed to facilitate the advance care planning with continuity of all the measures like symptom control or emotional, social and spiritual care of both the patient and the family during the disease steps like relapse or end of life.

Background: Previous studies have shown that children and adolescents with COVID-19 generally have mild disease. Children and adolescents with cancer, however, can have severe disease when infected with respiratory viruses. In this study, we aimed to understand the clinical course and outcomes of SARS-CoV-2 infection in children and adolescents with cancer. Methods: We did a cohort study with data from 131 institutions in 45 countries. We created the Global Registry of COVID-19 in Childhood Cancer to capture de-identified data pertaining to laboratory-confirmed SARS-CoV-2 infections in children and adolescents (

Palliative care (PC) is an approach that improves the quality-of-life (QoL) of patients and families facing problems associated with life-threatening illness. Pediatric palliative care (PPC) is the art and science of child-focused, family-oriented, relationship-centered medical care aimed at enhancing quality-of-life and minimizing suffering. In 2014, the Turkish Ministry of Health (TMH) published guidelines entitled “Directives for PC Services Implementation Procedures and Principles” to regulate the standards of PC. Although the number of PC units for adult patients increased rapidly after 2015, similar improvements did not occur in PPC. There are four recently established PPC units, and their inpatient hospital services take care of non-oncology PPC patients. Although there is still no PPC unit dedicated to children with cancer in Turkey, almost all pediatric hematologists and oncologists throughout Turkey provide some form of PC at their inpatient or outpatient oncology clinics. PPC should be included in the national health policies and education of healthcare workers.

Study Objective Rhabdomyosarcomas (RMSs) of the female genital tract (FGT) have been recently shown to be associated with germline pathogenic variation in DICER1, which can underlie a tumor predisposition disorder. We sought to determine the incidence of a pathogenic variation in DICER1 in a cohort of RMSs of the FGT, as well as to evaluate the clinicopathological features and outcomes of the patients. Design, Setting, Participants, Interventions, and Main Outcome Measures We retrospectively reviewed medical records of the patients diagnosed with RMS of the FGT between 1990 and 2019. Molecular genetic sequencing of the tumor to detect an RNase IIIb domain hot spot mutation in DICER1 samples was performed in 7 patients. Individuals with a missense mutation in the tumor were also screened for a loss of function germline mutation in DICER1. Results Of 210 cases of pediatric RMS, 11 arose from the FGT. Molecular genetic sequencing of the tumor samples revealed a somatic missense mutation in the RNase IIIb domain of DICER1 in a total of 3 patients, 2 patients with embryonal RMS of the cervix/uterus, and 1 patient with ovarian embryonal RMS. As a result of genetic testing for the loss of function germline mutation in DICER1, a heterozygous pathogenic variant was also found in 2 of these patients. Conclusion Despite the limited number of patients, our findings suggest that it is important to be aware of the possible association between RMS of FGT and pathogenic germline DICER1 variants because the detection of this mutation in a patient or relatives can provide the opportunity for surveillance of related conditions that might improve long-term outcomes and survival.

BACKGROUND: Polymerase chain reaction (PCR) respiratory viral panel (RVP) testing is often used in evaluation of pediatric cancer patients with febrile neutropenia (FN), but correlation with adverse outcomes has not been well characterized. PROCEDURE: A retrospective cohort of all children ages 0–21 with cancer admitted to Children’s Healthcare of Atlanta for FN from January 2013 to June 2016 was identified. Patient demographic and clinical variables such as age, RVP results, length of stay (LOS), and deaths were abstracted. Relationship between RVP testing and positivity and LOS, highest temperature (Tmax), hypotension and ICU admission were compared using Wilcoxon rank sums, Chi-square, or Fisher’s exact tests adjusting for age, sex, bacteremia, and diagnosis. RESULTS: The 404 patients identified had 787 total FN admissions. RVPs were sent in 38% of admissions and were positive in 59%. Patients with RVPs sent were younger (median 5.5 vs. 8.0 years, p

Germline biallelic mutations in one of the mismatch repair genes, mutS homolog 2, mutS homolog 6, mutL homolog 1, or postmeiotic segregation increased 2, result in one of the most aggressive cancer syndromes in humans termed as constitutional mismatch repair deficiency (CMMRD). Individuals with CMMRD are affected with multiple tumors arising from multiple organs during childhood, and these individuals rarely reach adulthood without specific interventions. The most common tumors observed are central nervous system, hematological, and gastrointestinal malignancies. The incidence of CMMRD is expected to be high in low-resource settings due to a high rate of consanguinity in these regions, and it is thought to be underrecognized and consequently underdiagnosed. This position paper is therefore important to provide a summary of the current situation, and to highlight the necessity of increasing awareness, diagnostic criteria, and surveillance to improve survival for patients and family members.

Document Information Language:English Accession Number: WOS:000546013100075 PubMed ID: 32565997, Retinoblastoma is a tumor of the embryonic neural retina in young children. The DNA methyltransferase 1 (DNMT1) gene has been demonstrated to be transcriptionally activated in cells lacking retinoblastoma 1 (RB1). Thus, there is a direct interaction betweenDNMT1andRB1 in vivo. The present study hypothesized that uncontrolledDNMT1, DNMT2andDNMT3expression may lead to a high level of global genome methylation causing a second hit or where both alleles are altered, inRB1and/or inactivation of other genes in retinal cells. To test this, the global genome methylation levels were analyzed in 69 patients with retinoblastoma, as well as 26 healthy siblings and 18 healthy unrelated children as the control groups. Peripheral blood and tumor tissue samples were obtained from 32 patients. The expression levels ofDNMTgenes were also determined in cell lines. Based on the median levels of global genome methylation in patients, higher genome-wide methylation levels in peripheral blood were associated with a 3.33-fold increased risk for retinoblastoma in patients compared with all healthy controls (95% confidence interval, 0.98-11.35; P, This study was funded by Istanbul University with project number BAY:TAS-2017-23070, Istanbul University-Cerrahpasa with project number BYP-2019-32977 and the AVON-AACR foundation with grant number 2005-2007.