We report the case of a 6‐year‐old female with xeroderma pigmentosum (XP) who developed a nonoperable scalp tumor, treated with anti‐programmed cell death protein 1 (anti‐PD‐1) therapy ...(nivolumab). She presented with a sarcomatoid carcinoma of the scalp with bone lysis as well as vascular and meningeal contact. Nivolumab was initiated because it has emerged as a promising immunotherapy. We observed a dramatic tumor response with excellent tolerance. However, while on nivolumab therapy she developed two large skin melanomas and several squamous cell carcinomas, which have been resected. These results demonstrate that cancer immunotherapy in patients with XP can be impressive but complex and warrants further investigation.
Imatinib is the standard of care in adults with chronic myeloid leukemia (CML) in chronic phase (CP). Only a few studies to assess efficacy in children have been performed. We report on the results ...of the French prospective trial (ClinicalTrials.gov identifier NCT00845221) conducted in children and adolescents with newly diagnosed CML in CP.
A total of 44 patients from age 10 months to 17 years with newly diagnosed CML in CP received daily imatinib 260 mg/m(2). Progression-free survival, responses, and tolerance were evaluated.
With a median follow-up times of 31 months (range, 11 to 64 months), the estimated progression-free survival rate at 36 months was 98% (95% CI, 85% to 100%). A complete hematologic response was achieved in 98% of the patients. The rates of complete cytogenetic response (CCyR) and major molecular response (MMR) were 61% and 31% at 12 months, respectively. During follow-up, CCyR and MMR were achieved in 36 children (77%) and 25 children (57%), respectively. Overall, 30% of the patients discontinued imatinib, mainly because of unsatisfactory response. The most common adverse events were neutropenia and musculoskeletal events.
Imatinib is effective in children with CML in CP with response rates similar to rates reported in adults. The adverse effects are acceptable, but longer follow-up studies are required to fully assess the long-term impact.
Objectives
Recent progress in the understanding of tumor biology and new targeted therapies has led to improved survival in adults with malignant melanoma (MM). MM is rare in children, especially ...before puberty. We report here our experience with pediatric patients with MM, describe the clinical presentation, treatment and evolution, and compare prepubescent and postpubescent disease.
Methods
A retrospective, descriptive, national multicenter study was undertaken of 52 cases of MM in children and adolescents. Demographic, histopathology, treatment evolution data, and survival distributions are described.
Results
Median age was 15 years (5–18). The tumors were often amelanotic (45%) and raised (83%), and Breslow thickness was greater than 4 mm in 35% of cases. Histological examination showed superficial spreading (n = 16) or spitzoid (n = 16) or nodular (n = 9) pattern. Twelve children (23%) were less than 10 years of age. The spitzoid histotype was more frequent in prepubescent children (seven of 12). Seventeen patients relapsed, of whom four had skin lesions initially diagnosed as benign. Ten patients died after relapse. Five‐year event‐free survival and overall survival were 62.7% (95% confidence interval CI: 45.3–76) and 75.5% (95% CI: 56.8–87.1), respectively.
Conclusions
MM appears to be different in prepubescent children, of whom most had a spitzoid histotype. Diagnosis can be difficult, leading to delay in treatment. New biological tools to identify targets for treatment in MM and to differentiate spitzoid melanomas from Spitz nevi now exist. As effective targeted therapies are now available, we recommend requesting biological examination of all melanocyte‐derived skin lesions in children that could be malignant.
Genome-wide association studies (GWAS) have identified that frequent polymorphisms in ARID5B and IKZF1, two genes involved in lymphoid differentiation, increase the risk of childhood acute ...lymphoblastic leukemia (ALL). These findings markedly modified the current field of research on the etiology of ALL. In this new context, the present exploratory study investigated the possible interactions between these at-risk alleles and the non-genetic suspected ALL risk factors that were of sufficient prevalence in the French ESCALE study: maternal use of home insecticides during pregnancy, preconception paternal smoking, and some proxies for early immune modulation, i.e. breastfeeding, history of common infections before age one year, and birth order. The analyses were based on 434 ALL cases and 442 controls of European origin, drawn from the nationwide population-based case-control study ESCALE. Information on non-genetic factors was obtained by standardized telephone interview. Interactions between rs10740055 in ARID5B or rs4132601 in IKZF1 and each of the suspected non-genetic factors were tested, with the SNPs coded as counts of minor alleles (trend variable). Statistical interactions were observed between rs4132601 and maternal insecticide use (p = 0.012), breastfeeding p = 0.017) and repeated early common infections (p = 0.0070), with allelic odds ratios (OR) which were only increased among the children not exposed to insecticides (OR = 1.8, 95%CI: 1.3, 2.4), those who had been breastfed (OR = 1.8, 95%CI: 1.3, 2.5) and those who had had repeated early common infections (OR = 2.4, 95%CI: 1.5, 3.8). The allelic ORs were close to one among children exposed to insecticides, who had not been breastfed and who had had no or few common infections. Repeated early common infections interacted with rs10740055 (p = 0.018) in the case-only design. Further studies are needed to evaluate whether these observations of a modification of the effect of the at-risk alleles by non-genetic factors are chance findings or reflect true underlying mechanisms.
Very rare tumors (VRTs) in children and adolescents are orphan diseases defined by an annual incidence of <2/1000,000. For a long time, VRTs have been outside of clinical and research groups in the ...field of pediatric oncology. As a result, exchange of experience and development of therapeutic standards have not been promoted. After the foundation of several national VRT working groups and the European Cooperative Study Group on Pediatric Rare Tumors (EXPeRT), a virtual consultation system (VCS) has been established, which specifically aimed at facilitating access to clinical consultation in complicated cases of VRTs.
The VCS has been open to physicians. After initial registration, they can present VRT patients free of charge. Patient consent and data pseudonymization were mandatory. Within the VCS, disease specific interdisciplinary panel discussions with at least three experts from the EXPeRT group and partners have been opened, and at the end of the discussion, a written summary and recommendation was provided.
Between Mai 2017 and March 2023, 160 cases from 27 countries (20 European, 7 non-European) have been discussed in the VCS. The most common diagnoses were adrenocortical carcinoma, malignant skin tumors and malignant ovarian tumors. In a survey three months after panel discussion, more than 90% of requesting physicians evaluated the VCS to be easy to use, helpful and to have a significant impact on patient management.
A VCS may provide significant assistance in the management of children and adolescents with VRTs. Furthermore, it may help to overcome inequalities in access to adequate treatment in countries with lower health care system resources or without established VRT study groups. Therefore, EXPeRT will continue to support the VCS. For this purpose, the VRT panels have been integrated into the Clinical Patient Management System (CPMS) within the European Reference Network Initiative (ERN PAedCan).
•Very rare tumors (VRTs) in childhood and adolescence are orphan diseases.•Pediatric oncologists have limited experience in managing VRTs.•An international virtual consultation system (VCS) has been established for VRTs.•160 VCS consultations for VRTs illustrate the ability to promote quality of care.
Very rare tumors (VRTs) in pediatric age represent many different diseases. They present an annual incidence < 2/1000,000 and correspond to about 11% of all cancers in patients aged 0–14 years. They ...can be roughly divided into two groups: one including tumors that are also rare in adults, and the other group includes adult-type tumors rarely encountered in children and adolescents. Although there is an obvious gap in knowledge regarding oncogenesis in pediatric cancers, there is some evidence of the involvement of various signalling pathways in the development of tumors in children and adolescents and sometimes in young adults. In addition, despite the rarity of these neoplasms, several attempts have been made to disclose the underlying mechanisms. More effort and resources have urgently to be devoted to deepening current knowledge and integrating new findings into the therapeutic approach, which nowadays relies on the treatment modalities used in adult oncology. The aim of this paper is to provide a review of the main solid VRTs occurring in both the pediatric and the adult age groups, highlighting the variability between groups in their biological and clinical course.
•Very rare tumors correspond to about 11% of all pediatric cancers.•Most pediatric VRTs are frequent in adulthood.•Biological features vary in the pediatric group.•Biological and clinical differences should lead to age-tailored treatment.
Olfactory neuroblastoma (ON) is a rare tumor commonly presenting between 50 and 60 years of age. In pediatric age this tumor is even rarer, with an estimated incidence of 0.1 per 100,000 children up ...to 15 years. It arises from the olfactory neurorepithelium of the nasal cavity, and it can be locally aggressive, spreading to the orbital cavity, skull base, intracranial cavity. In rarer cases it can also give distant metastasis, more frequently to regional lymph nodes and less commonly to distant sites like liver, lungs and bones. Prognosis varies depending on the stage at presentation (including dural invasion, regional nodal involvement, and distant metastasis), the histological grade, and aspects related to the treatment, such as the possibility to achieve clear margins with surgery and the multimodal approach. Chemotherapy, surgery and radiotherapy have been used to treat these patients and the different approaches have been reported in the literature. Given the rarity of the disease no shared guidelines exist for the management of this entity in children, but some suggestions can be given to optimize the ON management.
This study presents the internationally recognized recommendations for the diagnosis and treatment of ON in children and adolescents, established by the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT) group within the EU-funded project Pediatric Rare Tumors Network - European Registry (PARTNER).
•Olfactory neuroblastoma is a very rare tumor.•Children often present with local advanced stage.•Multimodal therapy should be considered as the best approach.•Relapse occurs often in the first year after diagnosis.•Functional sequelae related to surgery and radiotherapy are common.
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