Adjuvant and neoadjuvant chemotherapy in osteosarcoma.

Associated chemotherapy (adjuvant or neoadjuvant) means the association of systemic pharmacological therapy to local therapy in the treatment of tumors that, although appearing to still be localized at the time of diagnosis, have a high probability of having already given systemic micrometastases. The purpose of this kind of treatment is that of controlling the micrometastases present, even if they can't be documented, in many tumors. These neoplasms, although still apparently localized, do not achieve healing with the simple removal of the primary tumor, precisely because of the presence of these micrometastases. The current treatment of osteosarcoma (OS) commonly makes use of these therapies. There are different types of OS and they are not indicated in all associated therapies, nor do they provide the same results. We may begin by distinguishing between "high-grade" forms, which have a considerable tendency to early metastasis (about 96% of cases) and "low-grade" forms, generally characterized by local malignancy alone (about 4% of cases). Based on the site on which they occur, OS may be "primary," that is, occurring on apparently normal bone (about 95% of cases) and "secondary," that instead occur on bone that is in some way already changed (as a result of radiation, infarction, Paget's disease, etc.). Based on the site and on the staging, OS can be subdivided into forms of the limbs (75% of cases) and "forms of the axile skeleton" (25% of cases) and in forms that are "still localized" at the time of diagnosis (80% of cases) and in forms "with metastases that are documented at the onset (20% of cases). The present review only concerns primary high-grade OS of the limbs that were not metastatic on diagnosis, representing about 60% of all OS, and it is based on the experience of the Rizzoli Orthopaedic Institute where, between 1983 and 1996, a total of 731 patients were treated by neoadjuvant chemotherapy using five different protocols that were subsequently activated (Table I).