Extra-appendiceal neuroendocrine neoplasms in children - data from the GPOH-MET 97 Study.

Neuroendocrine neoplasms (NEN) in children are rare. In Germany, children with NEN of the gastroenteropancreatic system are prospectively registered since 1997. The objective of this study was to evaluate diagnostics, treatment and outcome in children with extra-appendiceal NEN.Clinical data of 39 patients with NEN registered in the GPOH-MET 97 trial from 1997 to 2012 were analyzed. Children with NEN of the appendix were excluded.14 patients with pancreatic, 12 patients with bronchial, 6 patients with gastrointestinal, 2 patients with nasopharyngeal and 5 patients with NEN of unknown primary were registered. About half of the patients had localized disease and rather low grade tumors, including all bronchial NEN, 5 of 14 pancreatic and 2 of 6 gastrointestinal tumors. Metastatic disease and high grade tumors were stated in cases with nasopharyngeal tumors, NEN of unknown -primary and in part of pancreatic and gastrointestinal NEN. Complete surgical resection was performed in patients with localized NEN with an overall survival of 100%. In contrast, overall survival in metastatic disease was 26%.Outcome in children with low grade NEN and localized disease is excellent. Management of high grade tumors and metastatic disease remains challenging. Establishing international registries is inevitable for further improvements.

Systemic treatment of adrenocortical carcinoma in children: data from the German GPOH-MET 97 trial.

BACKGROUND: Adrenocortical cancer (ACC) in childhood is a rare disease with poor prognosis. Complete surgical resection, systemic chemotherapy, and mitotane therapy are important curative treatment options for patients with advanced-stage tumors. Since 1997, pediatric ACC patients in Germany have been treated according to the non-randomized, single arm study GPOH-MET-97. PATIENTS AND METHODS: Data regarding disease course, treatment, and survival rates of 60 patients (age 0.24-17.8 years) with ACC treated according to the GPOH-MET-97 protocol were collected and analyzed to determine outcome, with a focus on examining the effectiveness of mitotane therapy. RESULTS: Among all patients, event-free survival and overall survival were found to be 43.3% and 64.8%, respectively. Chemotherapy with VCR, IFO, ADR, CARBO, and VP16 had been provided to 34 patients (56.6%) in different settings (neoadjuvant, adjuvant, and salvage) and mitotane therapy to 32 patients (53.3%). Duration of mitotane treatment longer than 6 months and mitotane levels greater than 14 mg/l were found to be associated with significantly better survival. Local relapse was found to be associated with a worse prognosis compared to distant metastasis only. CONCLUSIONS: Systemic chemotherapy and mitotane therapy are important therapeutic options in the treatment of advanced pediatric ACC patients. Neoadjuvant therapy should be considered for patients with primarily incomplete resectable or inoperable tumors, and tumor spillage is an indication for adjuvant chemo- and mitotane therapy. All pediatric ACC patients should be treated in pediatric oncological centers according to a consistent protocol in a highly interdisciplinary setting.

Surgical aspects in the treatment of adrenocortical carcinomas in children: data of the GPOH-MET 97 trial.

Adrenocortical carcinomas (ACCs) are a rare entity, with an incidence of 1.5 per million population per year. The prognosis of ACC is poor. Complete surgical resection is essential for a curative approach and significantly determines overall prognosis. Tumor resection is sophisticated and complicated by the vulnerability of the tumor and its invasive growth. Chemotherapy and Mitotane are additional therapeutic approaches that are combined with surgery in an interdisciplinary strategy. In this study, 59 patients between 2 months and 18 years of age with histologically verified ACC were analyzed retrospectively with respect to oncosurgical aspects. Patients were registered in the GPOH-MET 97 trial of the Society of Pediatric Oncology and Haematology. Preoperative management, factors influencing surgical severity, and operative complications were assessed.The gender ratio was 1:2 (m:f). A total of 58 patients showed increased hormonal activity and associated clinical signs of hormonal excess. Tumor volume was ≥ 300 mL in 25 patients. These patients showed an increased rate of operative complications and a poorer overall survival (OS) rate (p<0.01). A total of 14 patients showed metastatic spread, particularly to the lungs and lymph nodes. Biopsy of the tumor was performed in 12 patients. Tumor rupture occurred in 11 patients. Preoperative biopsy and/or experienced tumor rupture were associated with poorer OS rate. R2 resection only was achievable in 5 patients, and surgery was not feasible in 3 patients.In conclusion, since most of the pediatric ACC are hormone active and can be diagnosed clinically, the need of a tumor biopsy has to be discussed critically. Thorough pre- and perioperative management is essential for oncosurgical success.

Ameloblastic fibro-odontoma: a clinicopathologic study of 12 cases.

OBJECTIVE: The ameloblastic fibro-odontoma (AFO) is an uncommon odontogenic tumor occurring in childhood with limited reported data on recurrence. The purpose of this AFO study was to review its clinicopathologic features, investigate treatment modalities and establish a recurrence rate. STUDY DESIGN: The clinicopathologic features of 12 new cases of AFO were analyzed and compared with those of 208 cases from the literature, with special emphasis on the clinical behavior, treatment, and recurrence rate. RESULTS: The average age was 9.4 (+/- 6.7) years with a male-to-female ratio of 1.6:1. The mandible was the site of occurrence in 59.5%. The tumor most often presented radiographically as a unilocular mixed density lesion associated with the crown of an impacted tooth. Displacement of teeth, delayed eruption and bony expansion were commonplace. There were 5 recurrences among 68 cases with adequate follow-up for a recurrence rate of 7.4%. All recurrences were attributed to incomplete removal at the time of the initial surgery. CONCLUSIONS: The AFO is a childhood tumor most often affecting the posterior jaws and frequently causing bony expansion with profound affects on the dentition. Conservative surgical removal with extraction of the associated teeth is recommended. The established recurrence rate is less than 10%.