Bone tumours in childhood and adolescence

Primary bone tumours are rare diseases in children and adolescence. Osteosarcoma and Ewing sarcoma are the commonest types of bone tumour in this age group. Whilst other rarer tumours occur their presentation and investigation are similar and their treatment will be individualised by specialist teams. We will therefore focus in on the challenges faced in the presentation, timely diagnosis, treatment and rehabilitation in young growing individuals with osteosarcoma and Ewing sarcoma.     

Children's Oncology Group's 2013 blueprint for research: Bone tumors

In the US, approximately 650 children are diagnosed with osteosarcoma and Ewing sarcoma (ES) each year. Five‐year survival ranges from 65% to 75% for localized disease and <30% for patients with metastases. Recent findings include interval‐compressed five drug chemotherapy improves survival with localized ES. In osteosarcoma a large international trial investigating the addition of ifosfamide/etoposide or interferon to standard therapy has completed accrual. For ES an ongoing trial explores the addition of cyclophosphamide/topotecan to interval‐compressed chemotherapy. Trials planned by the Children's Oncology Group will investigate new target(s) including IGF‐1R and mTOR in ES, and RANKL and GD2 in osteosarcoma. Pediatr Blood Cancer 2013; 60: 1009–1015. © 2012 Wiley Periodicals, Inc.     

Epidemiology of bone tumours in children and young adults

Although the epidemiology of malignant bone tumours in children and young adults has been explored, no definitive causation of any specific tumour has yet been identified. We performed a literature review (1970–2008) to find all papers covering possible aetiological factors involved in the development of bone tumours in children and young adults. Several associations have been reported with some consistency: the presence of hernias and Ewing sarcoma; high fluoride exposure and osteosarcoma; and parental farming and residence on a farm, younger age at puberty and family history of cancer for all bone tumours, especially osteosarcoma. Clearly further research is needed to confirm or refute these putative risk factors. It is likely that studies of gene–environment interactions may prove to be the most fruitful of future research. Pediatr Blood Cancer 2009;53:941–952. © 2009 Wiley‐Liss, Inc.     

Imaging of pediatric bone tumors: A COG Diagnostic Imaging Committee/SPR Oncology Committee White Paper

Malignant primary bone tumors are uncommon in the pediatric population, accounting for 3%–5% of all pediatric malignancies. Osteosarcoma and Ewing sarcoma comprise 90% of malignant primary bone tumors in children and adolescents. This paper provides consensus-based recommendations for imaging in children with osteosarcoma and Ewing sarcoma at diagnosis, during therapy, and after therapy.     

Quality of life of patients treated during childhood for a bone tumor: assessment by the Child Health Questionnaire

To determine which factors impact on quality of life of patients with bone tumor, we used the Children Health Questionnaire French version. Thirty-seven patients (25 males, 19 osteosarcoma, 18 Ewing sarcoma) were studied. At assessment, median age was 15 years, median follow-up was 4 years. Mean scores were 60, 81, 76, 74, 70, 87 for general health, physical functioning, pain, mental health, self-esteem, and family activity, respectively. Lower results were observed for mental health in girls, for physical functioning, and self-esteem in patients with endoprosthesis, and for family activity and pain in patients who had relapsed.     

Localised peripheral primitive neuroectodermal tumour (PNET) of the conjunctiva

A 16‐year‐old male presented with a 3‐month history of an asymptomatic, enlarging conjunctival lesion. An excisional biopsy was performed and histologic and immunohistochemical examination showed characteristic features of a peripheral primitive neuroectodermal tumour (PNET) adjacent to a benign compound naevus. FISH analysis, demonstrating a split‐signal at 22q12, confirmed the diagnosis. Staging investigations were negative confirming the primary nature of the lesion. The patient was treated with local wide re‐excision and chemotherapy. He remains alive and well 29 months after initial resection. Pediatr Blood Cancer 2009;53:669–671. © 2009 Wiley‐Liss, Inc.     

Malignant childhood tumours in Safdarjang Hospital

A retrospective analysis of the prevalence of malignant childhood tumours was made in children upto age group 15 years. Leukemias (29.2%), malignant lymphomas (15.4%), bone tumours (12.6%) and soft tissue sarcomas (8.2%) were the common malignancies encountered. Central nervous system tumours (5.4%) were less frequently seen, in contrast to certain western studies. It is proposed that a central childhood malignant tumour registry should be established for a population based study in India.     

Multimodal therapy for children and adolescents with Ewing Sarcoma: Results of the First National Chilean Trial (1986–1991)

Thirty-seven patients with Ewing sarcoma were treated in the First National Chilean Trial for Ewing's Sarcoma (1986–1991), which comprised the St. Jude Ewing's 78 Study. All patients received cyclophosphamide, doxorubicin, vincristine, and Dactinomycin for a total treatment period of about 10 months, and all prescribed therapy was administered. Local therapy consisted of irradiation (RT) to the primary tumor, complete surgical resection, or a combination of both surgery and RT. Twenty-nine of these patients had localized tumors, 24% had pelvic primary tumors, 21 were males, and 20 were greater than 10 years of age at diagnosis. Twenty-one patients had tumors that were greater than 8 cm in largest diameter. Fourteen of the 29 patients with localized disease remain disease free at 23 to 91 months from diagnosis. Fourteen patients have died oftumor-related complications and 1 of a secondary malignancy. Relapse was local only in 4, metastatic in 9, and local plus metastatic in 1. Only 1 of the 8 patients with metastatic disease at presentation remains disease free. Toxicity consisted primarily of myelosuppression and mucositis. We conclude that this form of relative intense multimodal therapy for children/adolescents with localized Ewing sarcoma is curative in about half of affected children as in the original St. Jude study, and that it can be safely given in a developing country, provided that careful attention to supportive care and treatment planning is given. Although these results represent improvement in outcome for our patients, more effective therapy is needed for children with Ewing sarcoma, especially those with metastatic disease at presentation. Med. Pediatr. Oncol. 29:190–196, 1997. © 1997 Wiley-Liss, Inc.     

18F-FluoroDeoxyGlucose Uptake of Bone and Soft Tissue Sarcomas in Pediatric Patients

A high ¹⁸F-fluorodeoxyglucose (FDG) uptake by positron emission tomography/computed tomography (PET/CT) imaging in sarcomas of adults has been reported. The current study aimed at defining the degree of ¹⁸F-FDG uptake of pediatric sarcomas. This retrospective study included 29 patients (23 males, 6 females; mean age 14 ± 5 years) with soft tissue (n = 9) or bone (n = 20) sarcomas. Twenty-two patients (76%) underwent ¹⁸F-FDG PET/CT and 7 (24%) had dedicated ¹⁸F-FDG PET studies. Tumor ¹⁸F-FDG uptake was quantified by standard uptake value (SUV)_max and tumor-to-liver ratios (SUV ratios; tumor SUV_max/liver SUV_mean). Tumor SUV_max and SUV ratios were correlated with tumor Ki-67 expression. SUV_max ranged from 1.4 to 24 g/mL (median 2.5 g/mL) in soft tissue sarcomas and 1.6 to 20.4 g/mL (median 6.9 g/mL) in bone sarcomas (P = .03), and from 1.6 to 9.2 g/mL (median 3.9 g/mL) and 3.5 to 20.4 g/mL (median 12 g/mL) in Ewing sarcoma and osteosarcoma, respectively (P = .009). Tumor SUV ratios ranged from 0.8 to 8.7 (median 1.9) in soft tissue sarcomas and 1.4 to 8.9 (median 3.8) in bone sarcomas (P = .08). Ewing sarcoma had a significantly lower tumor SUV ratio than osteosarcoma (P = .01). Ki-67 expression correlated significantly with the ¹⁸F-FDG uptake in bone but not in soft tissue sarcomas. All sarcomas were visualized by ¹⁸F-FDG PET/CT imaging. A higher ¹⁸F-FDG uptake was observed in osteosarcoma than in Ewing and soft tissue sarcomas. The results of this study suggest that the degree of tumor ¹⁸F-FDG uptake is sufficient to allow for monitoring of therapeutic responses in pediatric sarcomas.     

Imaging of liver tumours in childhood

Primary liver tumours account for 6% of all paediatric neoplasms. In a child with a clinical abdominal mass, imaging (in consultation with a paediatric surgeon) aims to confirm the intrahepatic site, determine its likely resectability, exclude metastatic abdominal disease, and characterise the mass. The imaging in 44 patients with primary liver tumour over a 33-year period was reviewed and correlated with surgical/pathological findings. Characterising hepatic masses with ultrasound, computed tomography, nuclear medicine, and angiography is less important than determining its resectability and alerting the surgeon to vascular anomalies and the presence of metastatic disease. We conclude that a chest X-ray and ultrasound study are the primary methods for evaluation of a child with suspected hepatic mass. With careful attention to technique, the mass can be evaluated and an assessment made of tumour resectability preoperatively. Based on this review, we propose a schema for the initial evaluation of suspected hepatic masses in children. Offprint requests to: J. F. de Ocampo     

Second malignant tumours in childhood Hodgkin's disease

This study was undertaken to determine the treatment-specific incidence of second malignant tumours (SMT) in childhood Hodgkin's disease. The institutional databases at The Hospital for Sick Children, the Princess Margaret Hospital, and the Toronto-Bayview Regional Cancer Centre were reviewed for the years 1958–1993. Three hundred and forty-three consecutive newly diagnosed children were evaluated. The overall 30 year cumulative SMT incidence was 31%. The 20 year SMT incidence was greater for patients who relapsed (n = 129), 27%, compared with patients who remained relapse free (n = 214), 13%. For patients with stage 1–3B disease who remained relapse free, the 10 year SMT rate was 7% for patients who were surgically staged and treated with extended field radiation treatment (EF RT) (35 G), compared with 3% in clinically staged patients treated with MOPP (six cycles) and EF RT (25–30 G). To date there is no significant difference in the oncogenicity of these treatment protocols. However, EF RT alone was less effective in disease control. For stages 1–3B, 62% of patients relapsed after EF RT alone compared with 18% after bimodal treatment. Therefore treatment intensification due to relapse was more frequent in the former group. The overall 10 year SMT incidence for patients treated with these protocols was 11% and 3%, respectively. The 20 year SMT incidence following EF RT alone was 24%. We conclude that SMTs were a common late complication in childhood Hodgkin's disease and are a limiting factor in the achievement of cure. The incidence of SMTs was increased in children who required retreatment and was minimal in children who remained in a first complete remission. Therefore the initial treatment strategy in childhood Hodgkin's disease must be to minimize the risk of relapse, in order to avoid the morbidity and mortality associated with both relapse and SMT induction, and to achieve this objective with a primary treatment protocol of low oncogenicity. © 1996 Wiley-Liss, Inc.     

Imaging guidelines for children with Ewing sarcoma and osteosarcoma: a report from the Children's Oncology Group Bone Tumor Committee

The Children's Oncology Group (COG) is a multi-institutional cooperative group dedicated to childhood cancer research that has helped to increase the survival of children with cancer through clinical trials. These clinical trials include a standardized regimen of imaging examinations performed prior to, during, and following therapy. This article presents imaging guidelines developed by a multidisciplinary group from the COG Bone Tumor Committee. These guidelines provide both required and recommended studies. Recommended examinations may become required in the future. These guidelines should be considered a work in progress that will evolve with advances in imaging and childhood cancer research.