Pediatr Blood Cancer 2010;55:652–654 Non-Metastatic Osteosarcoma of the Extremities in Children Aged 5 Years or Younger Massimo Eraldo Abate, MD, 1 * Alessandra Longhi, MD, 1 Stefano Galletti, MD, 2 Stefano Ferrari, MD, 1 and Gaetano Bacci, MD 1 Background. The occurrence of high-grade osteosarcoma is rare in children aged 5 years or younger and only limited series or case reports have been described. Methods. The records of patients aged 5 years or younger with non-metastatic high-grade osteosarcoma of the extremities treated with surgery and adjuvant or neo-adjuvant chemotherapy at Rizzoli Institute between 1972 and 1999 were ret- rospectively evaluated in relation to gender, primary tumor site, his- tological subtype, surgical treatment, chemotherapy-induced tumor necrosis, 5- and 10-year event-free survival (EFS), and rate of local recurrence. Data were compared to patients aged 6–40 years entered with the same diagnosis and over the same time interval. Results. Data from 20 patients were collected. Comparing these data with those from 1,106 patients 6–40 years of age only two main differences resulted: the younger group showed a higher rate for fibroblastic sub- type (P < 0.01) and for amputation surgery (P < 0.01). Among the two groups, no statistical difference was observed for the 5-year EFS (60% vs. 53.8%; P = 0.6) and 10-year EFS (60% vs. 52.1%; P = 0.5). The rate of local recurrence was 5.0% and 5.4%. Conclusions. These find- ings suggest that in non-metastatic osteosarcoma of the extremities outcome and clinical characteristics are similar among children 5 years of age or younger and older patients. However, in the younger group we have observed a significant higher rate of fibroblastic subtype as well as a significant higher rate of mutilating surgery. Pediatr Blood Cancer. 2010;55:652–654. © 2010 Wiley-Liss, Inc. Key words: chemotherapy; osteosarcoma; pediatric oncology; surgery INTRODUCTION High-grade central osteosarcoma is the most common primary skeletal tumor of childhood with an overall annual incidence of 5.6 cases per million of children under the age of 15 years [1–3]. The occurrence of high-grade central osteosarcoma is so rare in children aged 5 years or younger that so far only limited series or case reports have been described [4–12]. The aim of this study was to retrospectively evaluate the clinical characteristics and outcome of patients 5 years of age or younger with non-metastatic high-grade central osteosarcoma of the extremities, treated at our Institution with adjuvant or neo-adjuvant chemotherapy over a 27-year period. Data were compared to patients 6–40 years of age entered with the same diagnosis and over the same time interval. METHODS Patient Population Data were extracted from database including all patients aged less than 40 years with non-metastatic central high-grade osteosar- coma of the extremities entered at our Institution between 1972 and 1999. Records of 1,126 patients were reviewed. Patients were considered eligible for the adjuvant or neo-adjuvant protocols acti- vated in our Institution when they fulfilled the following criteria: typical radiographic and histologic features of high-grade central osteosarcoma of the extremities; no previous history of cancer and no prior chemotherapy and/or radiotherapy; age 40 years or less; no co-morbidity contraindicating the use of chemotherapy and no evidence of metastases at diagnosis. Twenty out of 1,126 patients (1.8%) were 5 years of age or younger and are the object of this analysis. The histological diagnosis of osteosarcoma, suggested by clini- cal and radiological findings, was confirmed on specimen obtained from an open or needle biopsy, and subsequently on tumor sur- gically removed, according to Fletcher et al. [13]. Osteosarcoma was classified as classic, telangectatic, and small cell osteosarcoma. On the basis of predominant cells and intercellular material, clas- sic osteosarcoma was noted to be osteoblastic, fibroblastic, and chondroblastic. Preoperative Evaluation A complete medical history was obtained from all patients who also underwent a thorough physical examination and several chem- ical laboratory tests. The primary tumor was evaluated on standard radiographs for the 274 patients entered before 1983 and with the addition of CT scan for the 852 patients entered later on. MRI was also performed in about half of all the 1,126 patients. Bone metas- tases were investigated by Technetium 99-MDP bone scan; standard radiographs of the chest and stratigraphy for those patients entered before 1983 and chest CT scan of thorax for those entered later were performed to exclude lung metastases. Chemotherapy Patients were treated according to 11 different protocols, 4 including adjuvant chemotherapy (1972–1982) and 7 including neo-adjuvant chemotherapy (1983–1999). These protocols were activated in consecutive periods and reported on detail in a previous paper [14]. Surgery and Pathological Evaluation of the Response to Chemotherapy The surgery intervention (amputation, rotation plasty, and limb salvage) was decided on the basis of the site and extension of 1 Department of Chemotherapy, Istituto Ortopedico Rizzoli, Bologna, Italy; 2 Ultrasound Section, Istituto Ortopedico Rizzoli, Bologna, Italy Conflict of interest: Nothing to report *Correspondence to: Massimo Eraldo Abate, SSD di Chemioter- apia, Istituto Ortopedico Rizzoli, Via Pupilli 1, 40136 Bologna, Italy. E-mail: massimo.abate@ior.it Received 10 February 2010; Accepted 15 March 2010 © 2010 Wiley-Liss, Inc. DOI 10.1002/pbc.22567 Published online 24 May 2010 in wileyonlinelibrary.com