Search

Primary lung carcinoma is an exceptionally rare childhood tumour, as per definition of the European Cooperative Study Group on Paediatric Rare Tumours (EXPeRT), with an incidence of 0.1-0.2/1,000,000 per year. Little is known about the clinical characteristics of children with primary lung carcinoma, a gap which this joint analysis of the EXPeRT group aimed to fill.We performed a retrospective case series of children (aged 0-18 years) with primary lung carcinoma, as collected through the EXPeRT databases between 2000 and 2021. We recorded relevant clinical characteristics including treatment and outcome.Thirty-eight patients were identified with a median age of 12.8 years at diagnosis (range: 0-17). Mucoepidermoid carcinoma (MEC) was the most frequent entity (n = 20), followed by adenocarcinoma (n = 12), squamous cell carcinoma (n = 4), adenosquamous carcinoma (n = 1) and small-cell lung cancer (n = 1). Patients with MEC presented rarely with lymph node metastases (2/20 cases). Overall, 19/20 patients achieved long-lasting remission by surgical resection only. Patients with other histologies often presented in advanced stages (14/18 TNM stage IV). With multimodal treatment, 3-year overall survival was 52% ± 13%. While all patients with squamous cell carcinoma died, the 12 patients with adenocarcinoma had a 3-year overall survival of 64% ± 15%.Primary lung carcinomas rarely occur in children. While the outcome of children with MEC is favourable with surgery alone, patients with other histotypes have a poor prognosis, despite aggressive treatment, highlighting the need to develop new strategies for these children, such as mutation-guided treatment.

Inborn and acquired deficits of type I interferon (IFN) immunity predispose to life-threatening COVID-19 pneumonia. We longitudinally profiled the B cell response to mRNA vaccination in SARS-CoV-2 naive patients with inherited TLR7, IRF7, or IFNAR1 deficiency, as well as young patients with autoantibodies neutralizing type I IFNs due to autoimmune polyendocrine syndrome type-1 (APS-1) and older individuals with age-associated autoantibodies to type I IFNs. The receptor-binding domain spike protein (RBD)-specific memory B cell response in all patients was quantitatively and qualitatively similar to healthy donors. Sustained germinal center responses led to accumulation of somatic hypermutations in immunoglobulin heavy chain genes. The amplitude and duration of, and viral neutralization by, RBD-specific IgG serological response were also largely unaffected by TLR7, IRF7, or IFNAR1 deficiencies up to 7 mo after vaccination in all patients. These results suggest that induction of type I IFN is not required for efficient generation of a humoral response against SARS-CoV-2 by mRNA vaccines. ispartof: JOURNAL OF EXPERIMENTAL MEDICINE vol:220 issue:1 ispartof: location:United States status: published

International audience; Introduction: Very rare pediatric tumors (VRTs), defined by an annual incidence ≤2 per million inhabitants, represent a heterogeneous group of cancers. Due to their extremely low incidence, knowledge on these tumors is scant. Since 2012, the French Very Rare Tumors Committee (FRACTURE) database has recorded clinical data about VRTs in France. This study aims: (a) to describe the tumors registered in the FRACTURE database; and (b) to compare these data with those registered in the French National Registry of Childhood Cancer (RNCE).Methods: Data recorded in the FRACTURE database between January 1, 2012 and December 31, 2018 were analyzed. In addition, these data were compared with those of the RNCE database between 2012 and 2015 to evaluate the completeness of the documentation and understand any discrepancies.Results: A total of 477 patients with VRTs were registered in the FRACTURE database, representing 97 histological types. Of the 14 most common tumors registered in the RNCE (772 patients), only 19% were also registered in the FRACTURE database. Total 39% of children and adolescent VRTs registered in the RNCE and/or FRACTURE database (323 of a total of 828 patients) were not treated in or linked to a specialized pediatric oncology unit.Conclusion: VRTs represent many different heterogenous entities, which nevertheless account for 10% of all pediatric cancers diagnosed each year. Sustainability in the collection of these rare tumor cases is therefore important, and a regular systematic collaboration between the FRACTURE database and the RNCE register helps to provide a more exhaustive picture of these VRTs and allow research completeness for some peculiar groups of patients.

Introduction: Childhood immune thrombocytopenia (ITP) is a rare autoimmune disorder characterized by isolated thrombocytopenia. Prolonged ITP (persistent and chronic) leads to a reduced quality of life for children in many domains. To provide optimal support for children, with ITP, it is important to be able to predict those who will develop prolonged ITP. This study aimed to develop a mathematical model based on platelet recovery that allows the early prediction of prolonged ITP. Methods: In this retrospective study, we used platelet counts from the six months following the diagnosis of ITP to model the kinetics of platelet evolution using a pharmacokinetic-pharmacodynamic model. Results: In a learning set (n=103), platelet counts were satisfactorily described by our kinetic model. The K parameter, which describes spontaneous platelet recovery, allowed a distinction between acute and prolonged ITP with an AUC of 0.74. In a validation set (n=58), spontaneous platelet recovery was robustly predicted using platelet counts from 15 (AUC=0.76) or 30 (AUC=0.82) days after ITP diagnosis. Discussion: In our model, platelet recovery quantified using the k parameter allowed prediction of the clinical course of ITP. Future prospective studies are needed to improve the predictivity of this model, in particular, by combining it with the predictive scores previously reported in the literature.

Therapeutic advances in pediatric oncology have made it possible to increase the five-year survival rate of 80% for all types of cancer, giving the possibility of a growing number of children reaching adulthood. This increase in the survival rate is not without cost for the survivors. The most common complications are endocrinopathies and affect approximately 50% of children cured of cancer. Overall mortality increases significantly over time : 6,5% at 10 years (confidence interval [CI] at 95%, 6,2-6,9), 11,9% at 20 years (CI at 95%, 11,5-12,4), and 18,1% at 30 years (CI at 95%, 17,3-18,9). Premature mortality is essentially due to a recurrence of the initial cancer, while late mortality is attributable to the consequences of treatment. Compared to children cured of cancer, adolescents and young adults have a lower risk of death due to later exposure to cancer treatment : 4,8 (CI 95%, 4,4-5,1) against 6,8 (IC 95%, 6,2-7,4), respectively. The psychological and social impact of the experience of cancer and its treatment is in the middle of the discussion. It is strongly recommended that adults cured of cancer benefit from a personalized follow up, according to a global approach. This follow up should be interdisciplinary and should focus on the prevention and management of late effects through screening, education on treatment-related complications, and should encourage preventive lifestyle behaviors.

Thyroid cancer is the first cause of endocrine malignancy among children. Over the past decades, an increase in the incidence rates (IR) has been observed around the world. Our study aimed to describe epidemiology, therapeutic management and survival rates of children and adolescents with thyroid cancer in France.A population-based study was conducted between 2000 and 2018 in children and adolescents less than 17 years with a diagnostic of thyroid cancer.A total of 774 thyroid cancers were included: 579 papillary (PTC), 83 follicular (FTC), and 111 medullary carcinomas (MTC). PTC are more frequent in females and in adolescents whereas MTC mainly concerned children, mostly with a familial predisposition. Almost all patients underwent thyroidectomy, completed for most patients with PTC and FTC by radioiodine therapy. Cervical dissection was performed more frequently in patients having PTC and MTC compared to those with FTC. Between 2000 and 2018, thyroid cancers IR in children fluctuated between 1.3 and 3.2 per million, without any significant trend. The median follow-up time was 11.3 years in children, and 5.7 years in adolescents. The 5year-OS was greater than 98.5%.Population-based studies are crucial for better understanding and delineation of best management of rare diseases as thyroid cancers in pediatric and adolescent population. Considering the very favorable survival, a stratification should be proposed between cases at low risk and cases at high risk of relapse, in order to consider a strategy of therapeutic de-escalation in the most favorable cases.

Noninfectious manifestations-allergy, autoimmunity/inflammation, lymphoproliferation, and malignancies-are known to exist in many primary immunodeficiency diseases (PID) and to participate in prognosis.To obtain a global view on their occurrence, we retrieved data from a retrospective cohort of 1375 patients included in the French National Reference Center for Primary Immune Deficiencies (CEREDIH) for whom we had a 10-year follow-up since inclusion in the registry.These patients were followed for 10 years (2009-2018) by specialized centers in university hospitals. This study showed that 20.1% of patients without prior curative therapy (n = 1163) developed at least 1 manifestation (event) encompassing 277 events.Autoimmune/inflammatory events (n = 138) and malignancies (n = 85) affected all age classes and virtually all PID diagnostic groups. They were associated with a risk of death that occurred in 195 patients (14.2%) and were found to be causal in 43% of cases. Malignancies (odds ratio, 5.62; 95% confidence interval, 3.66-8.62) and autoimmunity (odds ratio, 1.9; 95% confidence interval, 1.27-2.84) were clearly identified as risk factors for lethality. Patients who underwent curative therapy (mostly allogeneic hematopoietic stem cell transplantation, with a few cases of gene therapy or thymus transplantation) before the 10-year study period (n = 212) had comparatively reduced but still detectable clinical manifestations (n = 16) leading to death in 9.4% of them.This study points to the frequency and severity of noninfectious manifestations in various PID groups across all age groups. These results warrant further prospective analysis to better assess their consequences and to adapt therapy, notably indication of curative therapy.

Resume Propos La valeur pronostique de la detection precoce d’une rechute de rhabdomyosarcome chez l’enfant et l’apport de la realisation d’examens systematiques de suivi n’ont pas ete evalues a ce jour en Europe. Materiel et methodes Les modalites diagnostiques des rechutes, la qualite du suivi et ses consequences pronostiques eventuelles ont ete analysees chez 99 patients de moins de 20 ans, en rechute d’un rhabdomyosarcome initialement localise, apres traitement dans 9 centres adherents a la Societe francaise des cancers de l’enfant. Resultats Cinquante-neuf rechutes ont ete diagnostiquees par un « symptome » evocateur, 12 devant des « signes physiques » decouverts lors d’une consultation systematique et 27 sur une « imagerie systematique » (1 donnee imprecise). La survie apres rechute a 3 ans est de 47,5 % (IC95 % : 37,1 %–57,1 %). Le diagnostic de rechute est etabli plus precocement dans le groupe « imagerie systematique » que dans les groupes « symptomes » et « signes physiques » (p= 0,025) avec detection de tumeurs de plus petite taille (≤ 5 cm : 100,0 % v. 60,9 % v 77,8 %, p= 0,007), mais sans impact significatif sur les possibilites de mise en seconde remission (RC2, 70,4 % v 50,8 % v 50,0 % p= 0,37) et la survie globale a 5 ans (47,1 % v 47,1 % v 48,6 % p= 0,94). Aucune association n’a ete etablie entre le caractere « optimal » (61 patients) ou « non » (38 patients) du suivi et la survie globale (a 5 ans, 46,5 % v 52,9 % ; p = 0,22). Conclusion Les methodes actuelles de surveillance radiologique systematique apres traitement d’un rhabdomyosarcome localise en premiere remission semblent ameliorer la precocite du diagnostic, mais pas le pronostic de la rechute, ni les possibilites de mise en remission et doivent donc etre remises en question.

We report herein the case of a 17-year-old female who presented with intracranial hypertension and diplopia. Magnetic resonance imaging showed a large left cystic and solid temporoparietal lesion, associated with an infiltrating lesion of the brainstem, hypointense in T1 and hyperintense in FLAIR sequences, without enhancement after injection of gadolinium. Complete resection of the parietal mass and biopsy of the brainstem lesion were performed. Histopathological analysis of the parietal mass showed glioblastoma (WHO grade IV) with no IDH1/2 or H3.3/H3.1 gene mutation detected by Sanger sequencing. Immunohistochemistry found the expression of the proteins of mismatch repair system. Whole exome and RNA sequencing identified a BRAF-V600E mutation. The brainstem lesion was a diffuse midline glioma, H3K27M-mutant (grade IV) according to the 2016 WHO classification. Pan-genomic SNP arrays of the 2 tumors showed distinct genetic alterations. The parietal glioblastoma displayed complex genomic alterations whereas the brainstem glioma harbored chromosome 7q gain, chromosome 9p and 10 losses, and RB, TP53 and CDKN2A homozygous deletions. The patient was treated by concomitant radiochemotherapy (according to Stupp protocol). After 12 cycles of temozolomide, there was complete remission persistant in the parietal lobe. The brainstem tumor was stable but progressed after 3 months of temozolomide discontinuation. Treatment with mTOR inhibitors was initiated. At 21-month follow-up, the patient remains with few symptoms. No predisposition syndrome was identified in the patient or her family. Concurrent glioblastomas with distinct driver gene mutations are exceptional.

Background After the completion of therapy, patients with localized rhabdomyosarcoma (RMS) are subjected to intensive radiological tumor surveillance. However, the clinical benefit of this surveillance is unclear. This study retrospectively analyzed the value of off‐therapy surveillance by comparing the survival of patients in whom relapse was detected by routine imaging (the imaging group) and patients in whom relapse was first suspected by symptoms (the symptom group). Methods This study included patients with relapsed RMS after the completion of therapy for localized RMS who were treated in large pediatric oncology hospitals in France, the United Kingdom, Italy, and the Netherlands and who were enrolled in the International Society of Paediatric Oncology Malignant Mesenchymal Tumor 95 (1995‐2004) study, the Italian Paediatric Soft Tissue Sarcoma Committee Rhabdomyosarcoma 96 (1996‐2004) study, or the European Paediatric Soft Tissue Sarcoma Study Group Rhabdomyosarcoma 2005 (2005‐2013) study. The survival times after relapse were compared with a log‐rank test between patients in the imaging group and patients in the symptom group. Results In total, 199 patients with relapsed RMS were included: 78 patients (39.2%) in the imaging group and 121 patients (60.8%) in the symptom group. The median follow‐up time after relapse was 7.4 years (interquartile range, 3.9‐11.5 years) for survivors (n = 86); the 3‐year postrelapse survival rate was 50% (95% confidence interval [CI], 38%‐61%) for the imaging group and 46% (95% CI, 37%‐55%) for the symptom group (P = .7). Conclusions Although systematic routine imaging is the standard of care after RMS therapy, the majority of relapses were detected as a result of clinical symptoms. This study found no survival advantage for patients whose relapse was detected before the emergence of clinical symptoms. These results show that the value of off‐therapy surveillance is controversial, particularly because repeated imaging may also entail potential harm., This study assesses the clinical value of radiological surveillance imaging in pediatric patients with rhabdomyosarcoma, which is routinely performed after the completion of therapy. In the majority of patients, relapse is detected because of symptoms, and there is no evidence that early detection by imaging results in improved survival.

Prognostic values of an early detection of a relapse after treatment of a localized rhabdomyosarcoma and the interest of performing systematic radiologic assessment after treatment have not yet been evaluated in Europe.Modalities of relapse of 99 patients under 20 years of age, after an initially localized rhabdomyosarcoma, treated in 9 French centers ("Société française des cancers de l'enfant" consortium) have been analyzed. Prognostic value of the protocol compliance during the observation period after therapy has been evaluated.Relapses have been diagnosed in 59 cases by a "symptom" the child was complaining of, in 12 cases because of "physical signs" detected during the clinical examination of a systematic consultation and in 27 cases thanks to "systematic follow-up imaging" (missing data: 1 case). Survival after relapse at 3 years was 47.5 % (IC95 %: 37.1 %-57.1 %). Diagnosis of the relapse is established earlier in the group "systematic imaging" rather than with other methods of detection ("symptom", "physical signs"), (P= 0.025), with detection of smaller tumors (≤ 5 cm ; 100.0 % vs. 60.9 % vs. 77.8 %, P= 0.007) but without possibility of reaching a second remission (70.4 % vs. 50.8 % vs. 50.0 % P= 0.37), nor significant impact on 5-year overall survival (47.1 % vs. 47.1 % vs. 48.6 % P= 0.94).Current methods of systematic surveillance after a first-line treatment of an initially localized rhabdomyosarcoma seem to improve the earliness of the diagnosis, but not the prognosis of the relapse.