Age-related biological differences in children's and adolescents' very rare tumors

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

Adrenocortical tumours in children and adolescents: The EXPeRT/PARTNER diagnostic and therapeutic recommendations

Adrenocortical tumours (ACTs) are rare during childhood. A complete surgical resection provides the best chance of cure, but the role and efficacy of the adjuvant therapy are still controversial. Various histologic criteria of malignancy for ACTs adopted in children do not facilitate comparative studies and are not completely shared. Therefore, a sharp demarcation between benign and malignant lesions has not been recognised, making it difficult to identify who potentially needs perioperative therapy. This manuscript presents the internationally harmonised recommendations for the diagnosis and treatment of ACTs in children and adolescents, established by the European Cooperative Study Group for Paediatric Rare Tumours (EXPeRT) group within the EU-funded project PARTNER (Paediatric Rare Tumours Network - European Registry)

The role of cancer predisposition syndrome in children and adolescents with very rare tumours

Germline predisposing pathogenic variants (GPVs) are present in approximately 8 to 10% of children with all cancer types. Very rare tumours (VRTs) represent many different diseases, defined with an annual incidence < 2 / 1,000,000, and correspond to 11% of all cancers in patients aged 0-14 years. Some of these VRTs, including cancer typical for adults, develop in children with a cancer predisposition syndrome (CPS). Classically, three situations lead to consider this association: Some patients develop a VRT for which histology itself strongly suggests a GPV related to a CPS; others are referred for germline genetic testing because of a family or personal history and finally, a systematic molecular genomic tumour analysis, reveals a PV typical to a CPS. Depending on the samples tested and type of analysis performed, information can be directly available about the germline status of such a PV. Depicting the association between CPS and VRT is clinically important as some of these tumour types require adapted therapy, sometimes in the frontline setting, and the proposal of a specific surveillance programme to detect other malignancies. The diagnosis of CPS necessitates a careful familial evaluation and genetic counselling regarding the risks faced by the child or other family members. The aim of this paper is to propose a literature review of solid VRTs occurring in paediatric and young adult patients associated with CPSs

Rationale for the treatment of children with CCSK in the UMBRELLA SIOP-RTSG 2016 protocol

The International Society of Paediatric Oncology-Renal Tumour Study Group (SIOP-RTSG) has developed a new protocol for the diagnosis, treatment, and follow-up monitoring of childhood renal tumours-the UMBRELLA SIOP-RTSG 2016 protocol (the UMBRELLA protocol). This protocol has been designed to continue international collaboration in the treatment of childhood renal tumours and will be implemented in over 50 different countries. Clear cell sarcoma of the kidney, which is a rare paediatric renal tumour that most commonly occurs in childre

The current status of treatment of Wilms′ tumor as per the SIOP trials

This paper attempts to briefly describe the International Society of Paediatric Oncology (SIOP) policy of treatment of nephroblastoma since first study (SIOP 1) launched in 1971 until today. It focuses on the advantages of the preoperative chemotherapy and the stratification of patients induced this way. Marked efficacy of the pretreatment opened the way for less aggressive surgical management also in case of the "so-called" regular unilateral cases: Nephron-sparing surgery and minimal invasive techniques will probably find its place in this field of pediatric surgical oncology; however, very careful selection of cases must be the priority

Minimally invasive nephrectomy for Wilms tumors in children - data from SIOP 2001

To analyse the surgical and oncological outcome of minimally invasive surgery (MIS) for tumor nephrectomy in Wilms tumor (WT) patients. WT patients from the SIOP 2001 trial, undergoing MIS for tumor nephrectomy were analyzed with regard to demographic characterization, surgical specifications, complications, and outcome. There were 24 children matching the inclusion criteria. Median age at operation was 40.35 months (14.3-65.4). All patients received preoperative chemotherapy. Median tumor volume was 177.5 ml at diagnosis (46.5-958) and 73.0 ml at surgery (3.8-776). There was one surgical complication (splenic injury), no intraoperative tumor rupture occurred. Abdominal stage was I in 14, II in 7, and III in 3 patients. Adequate lymph node sampling was performed in only 2 patients. One local relapse occurred. Event-free survival was 23/24, overall survival was 24/24, median follow up was 47 months (2-114). We present the largest series so far of minimally invasive nephrectomies for nephroblastoma based on a multinational trial. Treatment results were comparable to those of open surgery; however, experience of operating surgeons was generally high. Discipline of lymph node sampling was inadequate. Based on this analysis a prospective study on MIS in nephroblastoma is planned by the SIOP Renal Tumor Study Grou

Characteristics and outcome of stage II and III non-anaplastic Wilms' tumour treated according to the SIOP trial and study 93-01

Purpose: To determine the prognosis of children with stage II and III of low or intermediate risk histology (SIOP classification) in unilateral localised Wilms tumour (WT) after neoadjuvant chemotherapy according to the trial and study of the International Society of Paediatric Oncology, SIOP 93-01. Patients and methods: Patients with unilateral localised WT and stage II or III with low (LR) or intermediate risk (IR) histology between 6 months and 18 years of age, were selected from the total sample of patients registered in the SIOP 93-01 study between June 1993 and December 2001. All patients received 4 weeks of actinomycin-D/vincristine before surgery. Postoperative chemotherapy consisted of actinomycin-D, vincristine and epirubicin/doxorubicin for 27 weeks. Flank or whole abdomen irradiation was given for stage III. Event-free survival (EFS) and overall survival (OS) were analysed for various subgroups. Results: Of 1476 registered patients 594 (40%) met the inclusion criteria for this analysis. Four hundred and two (67%) had stage II disease and 563 (95%) had intermediate risk histology. Median tumour volume was 439 ml at diagnosis and 163 ml after preoperative chemotherapy. With a median follow-up of 8 years, 5-year EFS was 90% (95% confidence interval [95% CI]: 87-92%) and OS 95% (95% CI: 93-97%). Patients with stage III, blastemal type histology and a large volume at surgery had a worse outcome. Conclusion: Treatment for stage II and III LR or IR WT is successful in a neoadjuvant setting as advised by the SIOP. Stage, tumour volume and blastemal type histology are the most important prognostic factors. (C) 2012 Elsevier Ltd. All rights reserve

Refining risk stratification for pretreated localised wilms tumours: the SIOP renal tumours srudy group experience [Abstract]

Purpose: The SIOP WT 2001 trial introduced a new ‘high risk’ entity: ‘blastemal type’ WT. However, the largest absolute number of relapses among localised tumours emanates from the ‘intermediate risk’ histology subgroup. We therefore investigated whether different thresholds for percentage necrosis/blastema might improve risk stratification based on histological response to pre-operative chemotherapy. Method: Data on 2,071 patients with localised unilateral WT treated with preoperative chemotherapy in the SIOP 2001 trial (to Sept 2009) were analysed. Martingale plots of excess risk of relapse versus overall% necrosis or%blastema in the viable residue were interrogated for thresholds at which risk altered. Event free survival was analysed by Kaplan-Meier methods and subgroups compared by log rank. Results: For the entire group, 2yr EFS was 88.2% (95%CI:86.6–89.8) and 5yr OS: 93.7% (95% CI:92.2–95.2). Histological risk group was a better discriminator of outcome than tumour stage (2yr EFS low risk:95.9%, intermediate risk:89.8% and high risk:76.9%, p<0.001; 2yr EFS stage I:91.0%, stage II:87.8% and stage III:83.2% p<0.001). Martingale plots showed no threshold effect for%necrosis but a reduced risk of relapse in those with <20% blastema in the viable tumour, with a small but steadily increasing risk of relapse with >50% blastema. For intermediate risk tumours, there was a significant decrease in EFS with increasing% blastema (comparing 0–10%, 10–90%, 90–100%). This persisted in the regressive subtype but was at the borderline for statistical significance in the mixed subtype (p¼0.05). The worst outcome group had 2 yr EFS of 79%. Conclusion: Survival of blastema after pre-operative chemotherapy in Wilms tumour is a better prognostic factor than% necrosis. Improved definition of chemoresistant blastema requires molecular characterisation of the disrupted biological pathways to improve risk stratification and inform discussions of new therapeutic approaches for these higher risk tumours