Douglas J. Harrison

Current and future therapeutic approaches for osteosarcoma

ABSTRACT Introduction: Current treatment of osteosarcoma includes surgical resection of all gross disease in conjunction with systemic chemotherapy to control micro-metastatic disease. This yields a 5-year event free survival (EFS) of approximately 70% for patients with localized osteosarcoma while patients with metastatic or recurrent disease fare poorly with overall survival rates of less than 20%. Areas covered: This review outlines the current and future approach towards the treatment of osteosarcoma. A literature search was performed utilizing PubMed. Several recent clinical trials are reviewed in detail, as is innovative research evaluating novel agents and surgical techniques which hold promise. Expert commentary: The outcome for patients with osteosarcoma has not changed in several decades. This plateau in survival rates highlights the need for a novel approach towards research. There remains a great deal of interest in utilizing the very high risk population of recurrent osteosarcoma patients to rapidly and sequentially evaluate novel agents to determine if any of these agents hold promise. Several phase II studies are ongoing or in development that offer hope based on intriguing preclinical data. Furthermore, initiatives in obtaining specimens to further explore the genetic and immunological profile behind osteosarcoma will be essential towards identifying novel pathways and targets to exploit.

The Role of 18F-FDG-PET/CT in Pediatric Sarcoma

Considerable debate remains regarding how best to incorporate 18F-FDG-PET/CT into clinical practice for pediatric sarcomas. Although there is a clear role for 18F-FDG-PET/CT in staging pediatric sarcoma, the value of 18F-FDG-PET/CT in prognostication for pediatric sarcomas remains unclear. In osteosarcoma, Ewing sarcoma, and rhabdomyosarcoma, 18F-FDG-PET/CT may be most useful in the identification of skeletal metastases, where the literature consistently suggests that it has improved sensitivity and specificity as compared to bone scintigraphy. The role of the imaging modality in the identification of pulmonary metastatic disease is less clear. Further controversy exists regarding the use of 18F-FDG-PET/CT in predicting outcome. Several studies, particularly in osteosarcoma, suggest changes in the maximal standardized uptake value (SUVmax) that can predict histologic response following neoadjuvant chemotherapy as well as overall outcome. Conversely, studies are conflicting regarding the use of 18F-FDG-PET/CT as a prognostic tool in Ewing sarcoma and rhabdomyosarcoma. The role of 18F-FDG-PET/CT in pediatric nonrhabdomyosarcoma soft tissue sarcomas is unknown at this time. Although most studies have been small and retrospective, in certain histologic subtypes, there is a clear role for the use of this imaging modality. Additional prospective and larger studies are needed to fully determine how best to incorporate 18F-FDG-PET/CT into treatment regimens for pediatric sarcomas in the future.

Alveolar soft part sarcoma in children and young adults: A report of 69 cases

Alveolar soft part sarcoma (ASPS) is a rare mesenchymal tumor characterized by ASPL‐TFE3 translocation. Apart from complete surgical resection, there is no standard management strategy.

Pediatric Musculoskeletal Imaging

The use of PET/computed tomography (CT) for the evaluation and management of children, adolescents, and young adults continues to expand. The principal tracer used is 18F-fluorodeoxyglucose and the principal indication is oncology, particularly musculoskeletal neoplasms. The purpose of this article is to review the common applications of PET/CT for imaging of musculoskeletal issues in pediatrics and to introduce the use of PET/CT for nononcologic issues, such as infectious/inflammatory disorders, and review the use of 18F-sodium fluoride in trauma and sports-related injuries.

Malignant Transformation of Testicular Teratoma to PNET, Adenocarcinoma, and Osteosarcoma with Complete Remission after Surgery and Combination Chemotherapy in a Young Adult Male

Mixed germ cell tumors (GCT) with teratoma components can transform into somatic malignancies which can include histologies outside of traditional germ cell lineages. We describe a case of an 18-year-old man with a metastatic testicular GCT with both mature and immature teratoma components containing malignant transformation into multiple histologies including PNET in the primary testicular tumor and osteosarcoma in a separate pulmonary metastatic lesion. Management with targeted chemotherapy resulted in a durable remission. This is the first reported case that we know of a patient with primary PNET malignant transformation with subsequent metastatic transformation to osteosarcoma.

Two cases of humoral hypercalcemia of malignancy complicating infantile fibrosarcoma

We report two infants with infantile fibrosarcoma (IFS) complicated by severe hypercalcemia. Assessment demonstrated suppressed parathyroid hormone and 1,25‐dihydroxyvitamin D levels with elevated circulating levels of parathyroid hormone related protein, indicating the diagnosis of humoral hypercalcemia of malignancy (HHM). HHM is a paraneoplastic syndrome rarely associated with pediatric malignancies. Hypercalcemia manifested clinically with neurologic symptoms and soft tissue calcium deposition and required aggressive management with intravenous fluids, diuretics, and supplemental electrolytes. Following treatment with neoadjuvant chemotherapy, serum calcium levels precipitously declined requiring calcium repletion. These cases highlight the improvement of hypercalcemia secondary to HHM following chemotherapy.