Management of Nonconventional Osteosarcoma

Abstract

Osteosarcoma is the most common primary tumor of bone, yet its absolute incidence among malignant tumors is low. Within its strict histologic definition, osteosarcoma comprises a family of lesions with considerable diversity in histologic features and grade. Its prognosis is dependent not only on these parameters but also on its anatomic site. It may occur inside the bones in the intramedullary or intracortical compartment or on the surfaces of bones, and in extraosseous sites. The incidence of osteosarcoma in the general population is 2–3/million/year, but is higher in adolescence, in which the annual incidence peaks at 8–11/million/year at 15–19 years of age. Environmental and genetic factors have been identified to play a role in OS. Several familial syndromes have been associated with this disease. Many osteosarcoma variants have been described and subclassification include ; Telangiectatic, Small cell, Epithelioid, low grade central, Parosteal, Periosteal, High-grade surface, Intracortical, Multifocal, Extraskeletal and Gnathic osteosarcoma. Local pain, followed by localized swelling and limitation of joint movement, are the typical signs and symptoms of osteosarcoma. Multi-modal treatment of osteosarcoma is based on the use of chemotherapy along with radical surgery. Complete surgical removal of both the primary tumor as well as all the radiologically detectable metastases is a prerequisite for curative treatment. Furthermore, because almost all patients have microscopic pulmonary metastases at the time of diagnosis, the role of systemic chemotherapy is essential for long-term survival. Therapeutic approaches are generally based on various factors: tumor entity, tumor stage, age, gender, general condition, quality of life, life expectancy. There are three major therapeutic options for patients suffering from osteosarcoma: surgery, chemotherapy, and palliative radiotherapy.The standard treatment associates both neoadjuvant and adjuvant chemotherapies and surgical treatment. The surgical treatment of osteosarcoma consists of several options such as amputation, limb-salvage with endoprosthetic or biological reconstruction, rotationplasty, lung metastasectomy.The aim of surgery must be a complete tumor removal with a wide margin of normal tissue in order to avoid local recurrence and improve overall survival. The primary aim of the chemotherapy is to eradicate the pulmonary micrometastases.The current standard protocol for multi-agent chemotherapy (MAP) consists of doxorubicin, cisplatin and high-dose methotrexate (MTX) with leukovorin-rescue, ± ifosfamide. Pemetrexed (PMX) and liposomal muramyl tripeptide phosphatidyl ethanolamine (L-MTP-PE) are the novel chemotherapies. Combination of L-MTP-PE and MAP with ifosfamide is strongly expected to become a “routine” agent for the treatment of patients with osteosarcoma. Radiotherapy is more likely used in patients who have refused definitive surgery, require palliation or have lesions in axial locations. Radiotherapy can be given as; externally directed beams, Brachytherapy or intraoperative techniques, Conformal radiotherapy, Proton-beam radiotherapy, Intensity modulated photon/proton radiation therapy and Specific organ-seeking radioisotopes. New strategies and innovative therapeutic approaches are needed to further improve survival in patients with osteosarcoma. Several gene therapy strategies have been evaluated. Since mutations associated with Rb-pathway and p53 are frequent in OS, the mutation compensation approach has been studied as a potential treatment against OS. High-dose chemotherapy and radiometabolic treatment considered a new therapeutic approach for poor prognosis osteosarcoma. Follow-up evaluations must include examination of the involved extremity and imaging of the chest, with radiography or CT, to assess for metastasis.Rehabilitation is specific to the site of resection and the reconstruction.