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Background: Somatically acquired genomic alterations with MYCN amplification (MNA) are key features of neuroblastoma (NB), the most common extra-cranial malignant tumour of childhood. Little is known about the frequency, clinical characteristics and outcome of NBs harbouring genomic amplification(s) distinct from MYCN. Methods: Genomic profiles of 1100 NBs from French centres studied by array-CGH were re-examined specifically to identify regional amplifications. Patients were included if amplifications distinct from the MYCN locus were seen. A subset of NBs treated at Institut Curie and harbouring MNA as determined by array-CGH without other amplification was also studied. Clinical and histology data were retrospectively collected. Results: In total, 56 patients were included and categorised into 3 groups. Group 1 (n = 8) presented regional amplification(s) without MNA. Locus 12q13-14 was a recurrent amplified region (4/8 cases). This group was heterogeneous in terms of INSS stages, primary localisations and histology, with atypical clinical features. Group 2 (n = 26) had MNA as well as other regional amplifications. These patients shared clinical features of those of a group of NBs MYCN amplified (Group 3, n = 22). Overall survival for group 1 was better than that of groups 2 and 3 (5 year OS: 87.5%±11% vs 34.9%±7%, log-rank p<0.05). Conclusion: NBs harbouring regional amplification(s) without MNA are rare and seem to show atypical features in clinical presentation and genomic profile. Further high resolution genetic explorations are justified in this heterogeneous group, especially when considering these alterations as predictive markers for targeted therapy. [ABSTRACT FROM AUTHOR]

Background: Pleuropulmonary blastoma (PPB) is a rare childhood dysontogenetic intrathoracic neoplasm associated with an unfavourable clinical behaviour. Cases presentation: We report pathological and cytogenetic findings in two cases of PPB at initial diagnosis and recurrence. Both tumors were classified as type III pneumoblastoma and histological findings were similar at diagnosis and relapse. In both cases, conventional cytogenetic techniques revealed complex numerical and structural chromosomal abnormalities. Molecular cytogenetic analysis (interphase/metaphase FISH and multicolor FISH) identified accurately chromosomal aberrations. In one case, TP53 gene deletion was detected on metaphase FISH. To date, only few cytogenetic data have been published about PPB. Conclusion: The PPB genetic profile remains to be established and compared to others embryonal neoplasia. Our cytogenetic data are discussed reviewing cytogenetics PPBs published cases, illustrating the contribution of multicolor FISH in order to identify pathogenetically important recurrent aberrations in PPB. [ABSTRACT FROM AUTHOR]

Abstract: Background: Metronomic chemotherapy (MC) is the administration of chemotherapy at doses below the maximal tolerated dose on a frequent schedule of administration, with no prolonged drug-free breaks. Objective: The aim of this research was to assess the effectiveness and tolerance of a metronomic etoposide/ cyclophosphamide/celecoxib regimen in children and adolescents with refractory cancer. Methods: This retrospective, single-center study evaluated the use of MC with etoposide 25 mg/m2.d-1 (days 1-14), cyclophosphamide 25 mg/m2 d-1 (days 15-28), and celecoxib 100 to 400 mg/d (days 1-28), in children with refractory, or high-risk relapsing, cancer. Adverse events were determined through laboratory analyses and investigator observations. Results: From January 2005 to December 2007, 17 children and adolescents were treated. The best responses observed were stabilizations of the disease that lasted over 20 weeks in 7 patients (41%). Most importantly, in 4 patients (24%) antalgic treatment could be transiently diminished or stopped, and in 1 patient (6%) oxygen support could be stopped for several weeks. Four grade IV platelet toxicities were noted in 3 patients; 2 grade IV anemia occurred in 2 patients (who had platelet and red blood cell transfusions before initiation of treatment); and 1 patient had grade III neutropenia. No other grade III or IV toxicities were noted. Grade II alopecia and stomatitis were observed in 1 patient and grade II vomiting was observed in 2 patients. One patient with meningeal carcinomatosis developed bilateral subdural hematoma for which the role of MC could not be ruled out. Circulating endothelial cells were elevated in 3 out of 3 patients in whom they were quantified and who were progressing while under MC. Conclusion: The MC regimen we report here was associated with disease stabilization without major toxicities. This assessment of MC in children and adolescents warrants further studies. [Copyright &y& Elsevier]

COVID-19 infection in paediatric patients with cancer is severe or critical in 20% of the patients. It can therefore directly affect paediatric patients with cancer and/or their care. We aimed at evaluating the safety and efficacy of the BNT162b2 mRNA COVID-19 vaccine in adolescents and young adults (AYA) with solid tumour. This study includes a retrospective analysis of safety and efficacy of the BNT162b2 mRNA COVID-19 vaccine administered to patients, ≥16 years old, under treatment for a solid tumour or within 6 months after treatment from 15th February 2021 to 15th April 2021. Two administrations of the vaccine 3 weeks apart were given. Sera were tested for anti-SARS-Cov-2 immunoglobulin G (IgG) antibodies directed against the S1 domain of the spike protein. In case of positive serology, neutralisation of SARS-Cov-2 was tested. Twenty-three patients with solid tumours were identified and proposed to get vaccinated. Nine patients refused, and 1 previously developed COVID-19 infection with positive serology. At the time of writing, 13 patients (10 M/2 F; median age: 17) started vaccination. All patients received 2 injections except 2 patients who stopped vaccination because of tumour progression. Ten patients were under treatment (alone or in combination: chemotherapy: 7 patients [pts], immunotherapy: 2 pts, targeted therapy: 3 pts, follow-up: 3 patients). Overall, vaccines were well tolerated. Five patients did not report any side-effects after the first injection and 4 after the second injection. The main local reactivity symptom was mild pain at the site of injection (6 and 2 pts). Fatigue (2 pts and 5 pts) was the most frequent systemic symptom. One patient refused serology testing. All patients but 1 had pre-vaccination negative serology; 7 of 10 patients tested had positive serology before second vaccine injection, and 9 of 10 patients had positive serology one month after the second injection. All patients with seroconversion had positive COVID-19 neutralisation test. No patient developed COVID infections. We report the good safety profile and good efficacy of the BNT162B2 vaccine in AYA with solid tumours. Larger series and monitoring of the kinetics of anti-Sars-Cov-2 IgG antibodies for several months are mandatory to confirm these preliminary results and to determine long-term vaccination. • The mRNA COVID-19 vaccineFaces a high refusal rate in AYA. • The mRNA COVID-19 vaccine displays high efficacy especially in AYA when compared to adult with cancer. • The mRNA COVID-19 vaccine has a good safety profile in AYA. [ABSTRACT FROM AUTHOR]

Background: Somatically acquired genomic alterations with MYCN amplification (MNA) are key features of neuroblastoma (NB), the most common extra-cranial malignant tumour of childhood. Little is known about the frequency, clinical characteristics and outcome of NBs harbouring genomic amplification(s) distinct from MYCN. Methods: Genomic profiles of 1100 NBs from French centres studied by array-CGH were re-examined specifically to identify regional amplifications. Patients were included if amplifications distinct from the MYCN locus were seen. A subset of NBs treated at Institut Curie and harbouring MNA as determined by array-CGH without other amplification was also studied. Clinical and histology data were retrospectively collected. Results: In total, 56 patients were included and categorised into 3 groups. Group 1 (n = 8) presented regional amplification(s) without MNA. Locus 12q13-14 was a recurrent amplified region (4/8 cases). This group was heterogeneous in terms of INSS stages, primary localisations and histology, with atypical clinical features. Group 2 (n = 26) had MNA as well as other regional amplifications. These patients shared clinical features of those of a group of NBs MYCN amplified (Group 3, n = 22). Overall survival for group 1 was better than that of groups 2 and 3 (5 year OS: 87.5%±11% vs 34.9%±7%, log-rank p<0.05). Conclusion: NBs harbouring regional amplification(s) without MNA are rare and seem to show atypical features in clinical presentation and genomic profile. Further high resolution genetic explorations are justified in this heterogeneous group, especially when considering these alterations as predictive markers for targeted therapy. [ABSTRACT FROM AUTHOR]

Background: Filgrastim is an effective granulocyte colony-stimulating factor (G-CSF) used to reduce periods of neutropenia and the risk of infection after chemotherapy courses. Pegfilgrastim is a pegylated filgrastim with a longer plasma half-life that is administered once per cycle. Objective: The aim of this study was to compare the efficacy of pegfilgrastim and filgrastim administered after chemotherapy in children with Ewing sarcoma. Methods: We performed a retrospective chart review of pediatric patients with Ewing sarcoma. Every patient received both types of G-CSF in different treatment courses of chemotherapy, which consisted of vincristine, ifosfamide, doxorubicin, and etoposide (VIDE); vincristine, actinomycin D, and ifosfamide (VAI); or vincristine, actinomycin D, and cyclophosphamide (VAC). A single injection of pegfilgrastim 100 μg/kg SC or a daily injection of filgrastim 5 to 10 μg/kg SC was administered 48 to 72 hours after the completion of chemotherapy. The following data were collected from the medical charts: proportion of chemotherapy courses with grade 4 neutropenia, duration of grade 4 neutropenia, proportion with severe neutropenia, duration of severe neutropenia, proportion with febrile neutropenia, duration of antibiotic treatment, duration of hospitalization, and percentage of patients receiving transfusion. Grade 4 neutropenia was defined as an absolute neutrophil count of <500 × 109/L; severe neutropenia was defined as a count of <200 × 109/L. Adverse events were collected from the medical charts. Results: Twenty children were included (13 girls and 7 boys). The patients'' median age was 12.8 years (range, 9–17 years) and median weight was 45.2 kg (range, 28–90 kg). A total of 178 chemotherapy courses (108 VIDE; 70 VAI or VAC) were administered and evaluated, including 134 courses with pegfilgrastim and 44 courses with filgrastim. Considering all types of chemotherapy combined, those courses in which pegfilgrastim was used were associated with a significantly lower incidence of severe neutropenia (0.21 vs 0.85; P = 0.03), a shorter duration of severe neutropenia (0.49 vs 2.36 days; P = 0.01), and a shorter duration of antibiotic treatment (1.07 vs 4.22 days; P = 0.03) compared with courses treated with filgrastim. No statistically significant differences were observed for the proportion and duration of grade 4 neutropenia, proportion of febrile neutropenia, duration of hospitalization, or red blood cell and platelet transfusions. Adverse effects were few and comparable between pegfilgrastim and filgrastim. Conclusions: In this retrospective chart review of children with Ewing sarcoma, using pegfilgrastim after chemotherapy courses was associated with significantly reduced frequency and shorter duration of severe neutropenia compared with those courses followed by filgrastim. Randomized controlled trials are needed to confirm these preliminary observations. [Copyright &y& Elsevier]