Temperatures, diagnostics and treatment in pediatric cancer patients with fever in neutropenia, NCT01683370.

In pediatric oncology, there is no evidence-based definition of the temperature limit defining fever (TLDF), which itself is essential for the definition of fever in chemotherapy-induced severe neutropenia (FN). Lowering the TLDF can increase the number of FN episodes diagnosed. This prospective, single center observational study collected data on all temperature measurements, complete blood counts (CBCs), and measures of diagnostics and therapy performed at and after FN diagnosis in pediatric oncology patients using a high standard TLDF (39 °C ear temperature). In 45 FN episodes in 20 patients, 3391 temperature measurements and 318 CBCs, plus information on antibiotics, anti-fungal therapy, antipyretics, blood cultures taken and on discharge were collected. These data can mainly be used to study the influence of virtually lowering the TLDF on diagnostic measures, treatment and length of hospitalization in pediatric FN, which in turn are directly related to costs of FN therapy, and quality of life. This approach can be expanded to include as well different definitions of neutropenia

Genetic testing and surveillance in infantile myofibromatosis: a report from the SIOPE Host Genome Working Group

Abstract Infantile myofibromatosis (IM), which is typically diagnosed in young children, comprises a wide clinical spectrum ranging from inconspicuous solitary soft tissue nodules to multiple disseminated tumors resulting in life-threatening complications. Familial IM follows an autosomal dominant mode of inheritance and is linked to PDGFRB germline variants. Somatic PDGFRB variants were also detected in solitary and multifocal IM lesions. PDGFRB variants associated with IM constitutively activate PDGFRB kinase activity in the absence of its ligand. Germline variants have lower activating capabilities than somatic variants and, thus, require a second cis-acting hit for full receptor activation. Typically, these mutant receptors remain sensitive to tyrosine kinase inhibitors such as imatinib. The SIOPE Host Genome Working Group, consisting of pediatric oncologists, clinical geneticists and scientists, met in January 2020 to discuss recommendations for genetic testing and surveillance for patients who are diagnosed with IM or have a family history of IM/PDGFRB germline variants. This report provides a brief review of the clinical manifestations and genetics of IM and summarizes our interdisciplinary recommendations

Income in Adult Survivors of Childhood Cancer.

INTRODUCTION: Little is known about the impact of childhood cancer on the personal income of survivors. We compared income between survivors and siblings, and determined factors associated with income. METHODS: As part of the Swiss Childhood Cancer Survivor Study (SCCSS), a questionnaire was sent to survivors, aged ≥18 years, registered in the Swiss Childhood Cancer Registry (SCCR), diagnosed at age 4'500 CHF), even after we adjusted for socio-demographic and educational factors (OR = 0.46, p<0.001). Older age, male sex, personal and parental education, and number of working hours were associated with high income. Survivors of leukemia (OR = 0.40, p<0.001), lymphoma (OR = 0.63, p = 0.040), CNS tumors (OR = 0.22, p<0.001), bone tumors (OR = 0.24, p = 0.003) had a lower income than siblings. Survivors who had cranial irradiation, had a lower income than survivors who had no cranial irradiation (OR = 0.48, p = 0.006). DISCUSSION: Even after adjusting for socio-demographic characteristics, education and working hours, survivors of various diagnostic groups have lower incomes than siblings. Further research needs to identify the underlying causes

Fertility preservation for female patients with childhood, adolescent, and young adult cancer:recommendations from the PanCareLIFE Consortium and the International Late Effects of Childhood Cancer Guideline Harmonization Group

Female patients with childhood, adolescent, and young adult cancer are at increased risk for fertility impairment when treatment adversely affects the function of reproductive organs. Patients and their families desire biological children but substantial variations in clinical practice guidelines reduce consistent and timely implementation of effective interventions for fertility preservation across institutions. As part of the PanCareLIFE Consortium, and in collaboration with the International Late Effects of Childhood Cancer Guideline Harmonization Group, we reviewed the current literature and developed a clinical practice guideline for fertility preservation in female patients who were diagnosed with childhood, adolescent, and young adult cancer at age 25 years or younger, including guidance on risk assessment and available methods for fertility preservation. The Grading of Recommendations Assessment, Development and Evaluation methodology was used to grade the available evidence and to form the recommendations. This clinical practice guideline leverages existing evidence and international expertise to develop transparent recommendations that are easy to use to facilitate the care of female patients with childhood, adolescent, and young adult cancer who are at high risk for fertility impairment. A complete review of the existing evidence, including a quality assessment, transparent reporting of the guideline panel's decisions, and achievement of global interdisciplinary consensus, is an important result of this intensive collaboration.info:eu-repo/semantics/publishe

Temperatures, diagnostics and treatment in pediatric cancer patients with fever in neutropenia, NCT01683370.

In pediatric oncology, there is no evidence-based definition of the temperature limit defining fever (TLDF), which itself is essential for the definition of fever in chemotherapy-induced severe neutropenia (FN). Lowering the TLDF can increase the number of FN episodes diagnosed. This prospective, single center observational study collected data on all temperature measurements, complete blood counts (CBCs), and measures of diagnostics and therapy performed at and after FN diagnosis in pediatric oncology patients using a high standard TLDF (39 °C ear temperature). In 45 FN episodes in 20 patients, 3391 temperature measurements and 318 CBCs, plus information on antibiotics, anti-fungal therapy, antipyretics, blood cultures taken and on discharge were collected. These data can mainly be used to study the influence of virtually lowering the TLDF on diagnostic measures, treatment and length of hospitalization in pediatric FN, which in turn are directly related to costs of FN therapy, and quality of life. This approach can be expanded to include as well different definitions of neutropenia

Further evidence that the neurodevelopmental gene FBXW7 predisposes to Wilms tumor

Somatic variants in the NOTCH pathway regulator FBXW7 are frequently seen in a variety of malignancies. Heterozygous loss-of-function germline variants in FBXW7 have recently been described as causative for a neurodevelopmental syndrome. Independently, FBXW7 was also considered as a susceptibility gene for Wilms tumor due to a few observations of heterozygous germline variants in patients with Wilms tumor. Whether the same FBXW7 variants are implicated in both, neurodevelopmental delay and Wilms tumor formation, remained unclear. By clinical testing, we now observed a patient with neurodevelopmental delay due to a de novo constitutional mosaic FBXW7 splice site pathogenic variant who developed Wilms tumor. In the tumor, we identified a second hit frameshift variant in FBXW7. Immunohistochemical staining was consistent with mosaic loss of FBXW7 protein expression in the tumor. Our data support the role of constitutional FBXW7 pathogenic variants in both, neurodevelopmental disorder and the etiology of Wilms tumor. Therefore, Wilms tumor screening should be considered in individuals with constitutional or germline pathogenic variants in FBXW7 and associated neurodevelopmental syndrome

The influence of different fever definitions on diagnostics and treatment after diagnosis of fever in chemotherapy-induced neutropenia in children with cancer.

BACKGROUND There is no evidence-based definition of the temperature limit defining fever (TLDF) in children with neutropenia. Lowering the TLDF is known to increase the number of episodes of fever in neutropenia (FN). This study aimed to investigate the influence of a lower versus standard TLDF on diagnostics and therapy. METHODS In a single pediatric cancer center using a high standard TLDF (39°C tympanic-temperature) patients were observed prospectively (NCT01683370). The effect of applying lower TLDFs (range 37.5°C to 38.9°C) versus 39.0°C on these measures was simulated in silicon. RESULTS In reality, 45 FN episodes were diagnosed. Of 3391 temperatures measured, 193 were ≥39.0°C, and 937 ≥38.0°C. For persisting fever ≥24 hours, additional blood cultures were taken in 31 (69%) episodes in reality. This number decreased to 22 (49%) when applying 39.0°C, and increased to 33 for 38.0°C (73%; plus 11 episodes; plus 24%). For persisting fever ≥48 hours, i.v.-antibiotics were escalated in 25 (56%) episodes. This number decreased to 15 (33%) when applying 39.0°C, and increased to 26 for 38.0°C (58%; plus 11 episodes; plus 24%). For persisting fever ≥120 hours, i.v.-antifungals were added in 4 (9%) episodes. This number increased to 6 (13%) by virtually applying 39.0°C, and to 11 for 38.0°C (24%; plus 5 episodes; plus 11%). The median length of stay was 5.7 days (range, 0.8 to 43.4). In 43 episodes with hospital discharge beyond 24 hours, applying 38.0°C led to discharge delay by ≥12 hours in 24 episodes (56%; 95% CI, 40 to 71), with a median delay of 13 hours, and a cumulative delay of 68 days. CONCLUSION Applying a low versus standard TLDF led to relevant increases of diagnostics, antimicrobial therapy, and length of stay. The differences between management in reality versus simply applying 39.0° as TLDF reflect the important impact of clinical assessment

Absolute neutrophil counts in blood counts during FN (n = 295).

<p>Displayed are the absolute neutrophil counts up to 1 G/L.</p

Temperature measurements during FN (n = 3391).

<p>Temperature measurements during FN (n = 3391).</p

Proportion of FN episodes with modifications of management for persisting fever, in reality and virtually according to different TLDF.

<p>Displayed are the proportions, plus their 95% CI as vertical lines, of FN episodes with additional blood cultures taken, with an escalation of antibiotics and with adding on antifungals, respectively, for persisting fever. Squares indicate management in reality, and circles indicate management simulated, strictly applying Limit_Standard and different Limit_Low.</p