IgG subclass deficiency and vaccination antibody titers : a paediatric study

Date du colloque&nbsp;: 10/2008</p

Rare Cancers in Children - The EXPeRT Initiative: A Report from the European Cooperative Study Group on Pediatric Rare Tumors.

The low incidence and the heterogeneity of very rare tumors (VRTs) demand for international cooperation. In 2008, EXPeRT (European Cooperative Study Group for Pediatric Rare Tumors) was founded by national groups from Italy, France, United Kingdom, Poland and Germany. The first aims of EXPeRT were to agree on a uniform definition of VRTs and to develop the currently most relevant scientific questions. Current initiatives include international data exchange, retrospective and prospective studies of specific entities, and the development of harmonized and internationally recognized guidelines. Moreover, EXPeRT established a network for expert consultation to assist in clinical decision in VRTs

Selective IgG subclass deficiency in children with recurrent infections : clinical, biological and therapeutic relevance

Date du colloque&nbsp;: 10/2008</p

Ovarian Sertoli Leydig cell tumours in children and adolescents: An analysis of the European Cooperative Study Group on Pediatric Rare Tumors (EXPeRT).

OBJECTIVE: To analyse ovarian Sertoli-Leydig cell tumours (SLCTs) for potential prognostic markers and their use for treatment stratification. PATIENTS: Forty-four patients were included. Patients were prospectively reported to the German MAKEI (Maligne Keimzelltumoren) studies (n=23), French TGM protocols (n=10), Italian Rare Tumour Project (TREP) registry (n=6), and the Polish Pediatric Rare Tumour Study group (n=5). Tumours were classified according to World Health Organisation (WHO) and staged according to International Federation of Gynecological Oncology (FIGO). RESULTS: Median age was 13.9 (0.5-17.4) years. All patients underwent resection by tumour enucleation (n=8), ovariectomy (n=17), adenectomy isolated (n=18) or with hysterectomy (n=1). FIGO-stage: Ia 24pts., Ic 17pts., II/III 3pts. One patient had bilateral tumours. Four patients (stage Ia: 3, stage Ic: 1) developed a metachronous contralateral tumour. Otherwise, all stage Ia patients remained in complete remission. Among 20 patients with incomplete resection or tumour spread (stage Ic-III), eight relapsed, and five patients died. Eleven patients were initially treated with two to sixcycles of cisplatin-based chemotherapy. Of these, seven patients are in continuous remission. Poor histological differentiation was associated with higher relapse rate (5/13) compared to intermediate (3/18) and high differentiation (0/4). Tumours with retiform pattern or heterologous elements showed a high relapse rate, too (5/11). After a median follow-up of 62months, event-free survival is 0.70\ub10.07, relapse-free survival 0.81\ub10.06 and overall survival 0.87\ub10.05. CONCLUSIONS: Prognosis of SLCTs is determined by stage and histopathologic differentiation. Complete resection with careful avoidance of spillage is a prerequisite of cure. The impact of chemotherapy in incompletely resected and advanced stage tumours remains to be evaluated

The European Paediatric Rare Tumours Network - European Registry (PARTNER) project for very rare tumors in children

The PARTNER project (Paediatric Rare Tumours Network - European Registry) was launched in 2016. PARTNER aims to create a European Registry dedicated to children and adolescents with very rare tumors (VRT). It links existing national registries and provides a registry for those countries in which a VRT registry has not yet been created. This consortium is composed of the various national cooperative groups and their respective member institutions. The strategic value of this project is based on the Europe-wide data collection concerning the treatment of VRTs. These data are provided to experts and constitute the basis for new clinical practice guidelines for use by ERN (European Reference Network) and non-ERN institutions. The proposed tasks and milestones will increase collaboration in the field of pediatric oncology among member states and will also facilitate the inclusion of low health expenditure average rate (LHEAR) countries in this process. In addition, this project creates a platform for VRTs that may represent a model on how to elaborate a comprehensive approach (case registration, international case consultation and treatment recommendations, and website to provide information for parents/patients) for rare diseases

Cutaneous melanoma in children and adolescents: The EXPeRT/PARTNER diagnostic and therapeutic recommendations

Cutaneous melanoma is rare in children and, like other very rare pediatric tumors, it suffers from a shortage of knowledge and clinical expertise. The clinical management of pediatric melanoma is often challenging. Its clinical and pathological diagnosis may be difficult, and there is no standard treatment. In the absence of specific treatment guidelines, young patients are generally treated following the same principle as for adults, but concern remains about their access to clinical trials and new drugs, which have been shown to dramatically change the natural history of advanced melanoma. This paper presents the internationally recognized recommendations for the diagnosis and treatment of children and adolescents with cutaneous melanoma, established by the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT) within the EU-funded project called PARTNER (Paediatric Rare Tumours Network - European Registry). Main recommendations for melanoma are to discuss pediatric patients in multidisciplinary teams that include both pediatric oncologists and specialists in adult melanoma; to enroll patients in prospective trials, if available; to collect data in national\u2013international databases; and to develop an effective international collaboration between pediatric and adult melanoma groups in order to facilitate the transfer of potentially effective new agents from the adult to the pediatric setting

Thymoma and thymic carcinoma in children and adolescents: The EXPeRT/PARTNER diagnostic and therapeutic recommendations

Thymic tumors are epithelial tumors arising from the anterior mediastinum and constitute 0.2-1.5% of all adult malignancies but are exceptional in pediatric population. Thymic epithelial tumors (TETs) encompass a variety of histologic subtypes associated with different clinical outcomes. Due to its rarity in children, TETs' management requires a multidisciplinary approach. However, prognosis remains still poor, especially among patients with thymic carcinoma. This study presents the internationally recognized recommendations for the diagnosis and treatment of thymic tumors in children and adolescents, established by the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT) group within the EU-funded project Paediatric Rare Tumours Network - European Registry (PARTNER)

Pediatric Mesothelioma Tumors: The European Expert Group Contribution.

Background and Aims: In adults with mesothelioma, cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRSHIPEC) is a standard of care in limited tumor, but long-term survival is very uncommon. Very little is known about the characteristics of this tumor in the pediatric population. Methods: The EXPeRT group of very rare pediatric tumors reviewed retrospectively children and youths ( 6421 year) diagnosed in Europe with mesothelioma tumors treated between 1987 and 2018. Results: Thirty three patients were identified, 14 males and 18 females. Only one exposure to asbestos was documented. Primary tumor was located into the peritoneum (23 patients), pleura (2), vagina (2), pericardium (1), and in multiple sites (5). Histology was multicystic peritoneal mesothelioma (MCPM; 6 patients; median age 14.1year, range 2.2-21.1) or malignant (27 patients; median age 13.4 year, range 0.2- 18.7): epithelioid (21), biphasic (4) and unspecified (2). All patients with MCPM are alive despite 4 peritoneal relapses, after surgery (5 patients) and CRS-HIPEC (1pt). Metastasis at diagnosis were present in 9/27 patients with malignant mesothelioma. Among them, first line treatment was heterogeneous: preoperative chemotherapy (14 cases), exclusive surgery (3 cases), exclusive chemotherapy (5 cases), adjuvant chemotherapy (3 cases) or palliative (2 cases). Response rate to cisplatin-pemetrexed was 50% (6/12 cases) with no response to other regimens (0/12 cases). Two patients have long term tumor controlwith targeted therapy. CRS-HIPEC was performed in 19 patients (upfront 3 cases, after neoadjuvant therapy 12 patients, or after tumor progression 6 cases, including 3 twice). After a median follow-up of 6.7y (range, 0-20), 5 year overall and event free survivals are respectively 82.3% (95%IC 67.8-99.9) and 45.1% (95%IC 28.4-71.7). Conclusions: Pediatric Mesothelioma is exceptional and seems to be different from its adult counterpart with few asbestos exposures and a better outcome. Cisplatin-pemetrexed regimen showed some efficacy. Relapses could be salvaged with active therapy including CRS-HIPEC. Targeted therapy should be considered

Multicentric Castleman Disease in an HHV8-Infected Child Born to Consanguineous Parents With Systematic Review

International audienceChildhood multicentric Castleman disease (MCD) is a rare and unexplained lymphoproliferative disorder. We report a human herpesvirus-8 (HHV-8)-infected child, born to consanguineous Comorian parents, who displayed isolated MCD in the absence of any known immunodeficiency. We also systematically review the clinical features of the 32 children previously reported with isolated and unexplained MCD. The characteristics of this patient and the geographic areas of origin of most previous cases suggest that pediatric MCD is associated with HHV-8 infection. Moreover, as previously suggested for Kaposi sarcoma, MCD in childhood may result from inborn errors of immunity to HHV-8 infection

Adrenocortical Tumors in Children and Adolescents: The European PARTN-ER Project for Consensus Guidelines Development.

Background and Aims: Adrenocortical carcinomas (ACC) are rare diseases. Several collaborative studies performed over the last decades showed improved results compared to historical data, but standardized guidelines for diagnosis andmanagement of pediatric ACC are still unavailable. Methods: We present European consensus guidelines developed by the Cooperative Study Group for Pediatric Rare Tumors (EXPeRT) according to the ESMO scale, based on the evidence collected from published series, case reports and personal expertise. Results: ACT should be removed without rupture [Level V; Grade B]. Preferred option is open approach through a lateral transverse abdominal incision or a midline laparotomy in case of huge masses [Level IV; Grade B]. Mini-invasive surgery should be discouraged when volume exceeds 200cm3, suspicious regional nodal involvement and/or signs of local invasion are present [Level IV; Grade B]. All enlarged lymph nodes detected at radiology or intra-operatively should be removed [Level III; Grade A]. A systematic biopsy of the regional nodes should be performed, though they are not found suspicious pre- or intraoperatively [Level IV; Grade C]. Adjuvant therapy should be considered in advanced-stage ACT or in case of incomplete tumor resection [Level IV; Grade B]. First-line recommended regimen is CED (cisplatinum-etoposide-doxorubicin) plus mitotane [Level IV; Grade B]. For COG stage II tumors, mitotane is considered if several risk factors are associated: unfavorable histology (5-item score or Wieneke score >3), older age, hormonal secretion [Level IV; Grade C]. For unresectable tumors, gross/macroscopic residual disease, retroperitoneal lymph nodes involvement, CED with mitotane are considered [Level III; Grade B]. No data exist about the optimal duration of therapy. CED is usually scheduled in 6 to 8 cycles. Mitotane is continued for 1 to 2 years depending on patient\u2019s tolerance and compliance [Level IV; Grade C]. Conclusions: This European PARTN-ER project leads to a consensus strategy regarding the treatment of children and adolescents with ACC