Larotrectinib is a first-in-class, highly selective tropomyosin receptor kinase (TRK) inhibitor approved to treat adult and pediatric patients with TRK fusion-positive cancer. The aim of this study ...was to evaluate the efficacy and safety of larotrectinib in patients with TRK fusion-positive primary central nervous system (CNS) tumors.
Patients with TRK fusion-positive primary CNS tumors from two clinical trials (NCT02637687, NCT02576431) were identified. The primary endpoint was investigator-assessed objective response rate (ORR).
As of July 2020, 33 patients with TRK fusion-positive CNS tumors were identified (median age: 8.9 years; range: 1.3-79.0). The most common histologies were high-grade glioma (HGG; n = 19) and low-grade glioma (LGG; n = 8). ORR was 30% (95% confidence interval CI: 16-49) for all patients. The 24-week disease control rate was 73% (95% CI: 54-87). Twenty-three of 28 patients (82%) with measurable disease had tumor shrinkage. The 12-month rates for duration of response, progression-free survival, and overall survival were 75% (95% CI: 45-100), 56% (95% CI: 38-74), and 85% (95% CI: 71-99), respectively. Median time to response was 1.9 months (range 1.0-3.8 months). Duration of treatment ranged from 1.2-31.3+ months. Treatment-related adverse events were reported for 20 patients, with grade 3-4 in 3 patients. No new safety signals were identified.
In patients with TRK fusion-positive CNS tumors, larotrectinib demonstrated rapid and durable responses, high disease control rate, and a favorable safety profile.
The aim of this literature review was to explore the views of parents and children with type 1 diabetes mellitus regarding having a school nurse.
Six databases were selected for the analysis. The ...research strategy was based on the PICO model. The research participants were children with type 1 diabetes mellitus and/or their parents.
The present review of research papers includes 12 publications. The majority of works deal with the perspectives of children with type 1 diabetes and their parents on various aspects related to the role of a school nurse in the care of a child with type 1 diabetes:the presence of a school nurse;the role of a school nurse in the prevention and treatment of hypoglycaemia, in performing the measurements of blood glucose, and in insulin therapy;the role of a nurse in improving metabolic control of children with type 1 diabetes;a nurse as an educator for children with type 1 diabetes, classmates, teachers, teacher's assistants, principals, administrators, cafeteria workers, coaches, gym teachers, bus drivers, and school office staff;a nurse as an organiser of the care for children with type 1 diabetes.
According to parents and children with type 1 diabetes mellitus, various forms of school nurse support (i.e., checking blood glucose, giving insulin, giving glucagon, treating low and high blood glucose levels, carbohydrate counting) are consistently effective and should have an impact on the condition, improvement of metabolic control, school activity and safety at school.
Asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA), inhibitors of nitric oxide synthase, play important roles in many processes in the body. Most data in the literature concern ...their importance in adult chronic kidney disease (CKD). According to them, SDMA well reflects the glomerular filtration rate (GFR), and higher ADMA concentrations are associated with hypertension and higher mortality. In addition, both substances are recognised cardiovascular risk factors in CKD. The purpose of this review was to summarise the studies on dimethylarginines in renal diseases in children, about which we have much fewer data. The review focuses specifically on dimethylarginine’s relation to routinely used renal function parameters. Finally, we analysed 21 of the 55 articles published between 2003 and 2022 on dimethylarginines in kidney diseases in children (from birth to 18 years of age), obtained by searching PubMed/MEDLINE (search terms: “dimethylarginine” and “kidney”).
: According to a recent Cochrane systematic review, renal impairment can develop in 0-84% of childhood cancer survivors in the future. The renal function impairment in this patient group can be ...related to nephrectomy, nephrotoxic agents therapy, abdominal radiotherapy, and combinations of these treatment methods. In this study, in a population of patients after anti-neoplastic therapy, with particular emphasis on patients after Wilms' tumour treatment, we compared new substances which play role in the chronic kidney disease (CKD) pathogenesis (asymmetric dimethylarginine-ADMA, symmetric dimethylarginine-SDMA) with standard renal function markers (e.g., creatinine and cystatin C in serum, creatinine in urine, etc.) to assess the usefulness of the former.
: Eighty-four children, without CKD, bilateral kidney tumours, congenital kidney defects, or urinary tract infections, with a minimum time of 1 year after ending anti-neoplastic treatment, aged between 17 and 215 months, were divided into three groups: group 1-patients after nephroblastoma treatment (
= 21), group 2-after other solid tumours treatment (
= 44), and group 3-after lymphoproliferative neoplasms treatment (
= 19). The patients' medical histories were taken and physical examinations were performed. Concentrations of blood urea nitrogen (BUN), creatinine, cystatin C, C-reactive protein (CRP), ADMA, and SDMA in blood and albumin in urine were measured, and a general urine analysis was performed. The SDMA/ADMA ratio, albumin-creatine ratio, and estimated glomerular filtration rate (eGFR) were calculated. eGFR was estimated by three equations recommended to the paediatric population by the KDIGO from 2012: the Schwartz equation (eGFR1), equation with creatinine and urea nitrogen (eGFR2), and equation with cystatin C (eGFR3).
: Both the eGFR1 and eGFR2 values were significantly lower in group 1 than in group 3 (eGFR1: 93.3 (83.1-102.3) vs. 116.5 (96.8-126.9) mL/min/1.73 m
,
= 0.02; eGFR2: 82.7 (±14.4) vs. 94.4 (±11.9) mL/min/1.73 m
,
= 0.02). Additionally, there were weak positive correlations between SDMA and creatinine (
< 0.05, r = 0.24), and cystatin C (
< 0.05, r = 0.32) and weak negative correlations between SDMA and eGFR1 (
< 0.05, r = -0.25), eGFR2 (
< 0.05, r = -0.24), and eGFR3 (
< 0.05, r = -0.32).
: The usefulness of ADMA and SDMA in the diagnosis of renal functional impairment should be assessed in further studies. eGFR, calculated according to equations recommended for children, should be used in routine paediatric practice.
Germ cell tumors (GCTs) are a heterogenous group of neoplasms in children and young adults, in which serum tumor markers have been demonstrated to be highly sensitive diagnostic and monitoring tools. ...The known "old" serum biomarkers, alpha-fetoprotein (AFP), human choriogonadotropin (β-hCG) and lactate dehydrogenase (LDH), have some limitations in sensitivity and specificity. MIRNAs from the miR-371~373 (chromosomal locus 19q13.41) and miR-302/367 (4q25) clusters are universally over-expressed in malignant GCT tissue samples. The levels of miRNAs from these clusters are elevated in the serum. They seem to be highly sensitive and specific in malignant GCTs diagnosis and disease assessment during treatment and follow-up. The aim of our review was to present the role of serum tumor markers in the clinical staging, treatment monitoring and follow-up of pediatric patients with GCTs and show new possibilities. The serum levels of miRNAs seem to be a new, promising essential tool in the clinical management of GCTs.
Although isolated central nervous system (CNS) relapses are rare, they may become a serious clinical problem in intensively treated patients with high-risk neuroblastoma (NBL). The aim of this study ...is the presentation and assessment of the incidence and clinical course of isolated CNS relapses. Retrospective analysis involved 848 NBL patients treated from 2001 to 2019 at 8 centres of the Polish Paediatric Solid Tumours Study Group (PPSTSG). Group characteristics at diagnosis, treatment and patterns of relapse were analysed. Observation was completed in December 2020. We analysed 286 high risk patients, including 16 infants. Isolated CNS relapse, defined as the presence of a tumour in brain parenchyma or leptomeningeal involvement, was found in 13 patients (4.5%; 8.4% of all relapses), all of whom were stage 4 at diagnosis. Isolated CNS relapses seem to be more common in young patients with stage 4 MYCN amplified NBL, and in this group they may occur early during first line therapy. The only or the first symptom may be bleeding into the CNS, especially in younger children, even without a clear relapse picture on imaging, or the relapse may be clinically asymptomatic and found during routine screening. Although the incidence of isolated CNS relapses is not statistically significantly higher in patients after immunotherapy, their occurrence should be carefully monitored, especially in intensively treated infants, with potential disruption of the brain-blood barrier.
Patients with stage 3 neuroblastoma (NBL) according to International Neuroblastoma Staging System (INSS) without MYCN amplification represent a heterogenous group with respect to disease presentation ...and prognosis.
Retrospective analysis of 40 stage 3 patients with NBL without MYCN amplification was performed. The prognostic value of age at diagnosis (under 18 vs over 18 months), International Neuroblastoma Pathology Classification (INPC) diagnostic category and presence of segmental or numerical chromosomes aberrations were evaluated, as well as biochemical markers. Array comparative genomic hybridization (aCGH) for analyzing copy number variations and Sanger sequencing for ALK point mutations were done.
In 12 patients (two patients under 18 months), segmental chromosomal aberrations (SCA) were found and numerical chromosomal aberrations (NCA) were found in 16 patients (14 patients under 18 months). In children over 18 months SCA were more common (p=0.0001). Unfavorable pathology was significantly correlated with SCA genomic profile (p=0.04) and age over 18 months (p=0.008). No therapy failures occurred in children with NCA profile over or under 18 months or in children under 18 months, irrespective of pathology and CGH results. Three treatment failures occurred in the SCA group, in one patient CGH profile was not available. For the whole group at 3, 5 and 10-year OS and DFS were 0.95 (95% CI 0.81-0.99), 0.91 (95% CI 0.77-0.97) and 0.91 (95% CI 0.77-0.97), and 0.95 (95% CI 0.90-0.99), 0.92 (95% CI 0.85-0.98) and 0.86 (95% CI 0.78-0.97), respectively. DFS was significantly lower in the SCA group than in the NCA group (3-years, 5-years, and 10-years DFS 0.92 (95% CI 0.53-0.95), 0.80 (95% CI 0.40-0.95) and 0.60 (95% CI 0.16-0.87) vs 1.0, 1.0 and 1.0, respectively, p=0.005).
The risk of treatment failure was higher in patients with SCA profile, but only in patients over 18 months. All relapses occurred in children having obtained the complete remission, with no previous radiotherapy. In patients over 18 months, SCA profile should be taken into consideration for therapy stratification as it increases the risk of relapse and this group may require more intensive treatment.
IntroductionThe place of laparoscopy in the resection of Wilms' tumors has remained debatable, but evidence that neoadjuvant chemotherapy causes tumor shrinkage has made laparoscopic nephrectomy (LN) ...a feasible option. Laparoscopic nephron-sparing surgery (NSS) is technically very demanding and seems to be feasible and effective only when performed by a very experienced surgeon. AimWe report 7 cases of laparoscopic nephrectomy and 1 case of laparoscopic heminephrectomy for Wilms' tumor. Material and methodsForty-two consecutive children with primary renal tumor underwent nephrectomy between 2013 and 2020; 11 had an LN. Among them there were 8 children with Wilms' tumor, with age between 13 months and 7 years. All patients received neoadjuvant chemotherapy according to the current SIOP protocol. The mean tumor volume before and after chemotherapy was 174.4 ml (range: 14.7-501) and 32.8 ml (range: 4.3-68) respectively. ResultsSeven laparoscopic nephrectomies and one heminephrectomy were performed. No patient had an intraoperative tumor rupture. All children had an attempt of lymph node sampling (their number per pathology assessment was in the range 0-5). There were no intraoperative events. One complication after heminephrectomy occurred, which was urine leak. Five patients had stage I tumor and 3 had stage II. Seven patients had an intermediate-risk and one had a high-risk tumor. There were no local or distant relapses. All patients remained disease-free at a median follow-up of 71 months (range: 16-94). ConclusionsThis report demonstrates the feasibility of LN in children with Wilms' tumors. The patients should be carefully selected and specific training in laparoscopy is necessary, particularly with regard to laparoscopic heminephrectomy.
a single-centre experience in bi- and uni-segmentectomies for primary liver tumours in children.
This study included 23 patients that underwent (bi)segmentectomy. There were 15 malignant tumours ...(hepatoblastoma-13 patients), 7 benign tumours, and 1 calcifying nested stromal epithelial tumour.
The median tumour diameter was 52 mm (range 15-170 mm). Bisegmentectomy 2-3 was most frequently performed (seven patients), followed by bisegmentectomy 5-6 (four patients). The median operative time was 225 min (range 95-643 min). Intraoperative complications occurred in two patients-small bowel perforation in one and an injury of the small peripheral bile duct resulting in biloma in the other. The median resection margin in patients with hepatoblastoma was 3 mm (range 1-15 mm). Microscopically negative margin status was achieved in 12 out of 13 patients. There were two recurrences. After a median follow-up time of 38 months (range 12-144 months), all 13 patients with HB were alive with no evidence of disease. Two relapsed patients were alive with no evidence of disease.
From the available literature and data presented here, we propose that (bi)segmentectomy can become a viable surgical option in carefully selected paediatric patients and is sufficient to achieve a cure. Further studies evaluating the impact of parenchymal preservation surgery on surgical and oncological outcome should be conducted with a larger dataset.
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