Primary osteogenic sarcoma. The rationale for preoperative chemotherapy and delayed surgery

Abstract

From 1973From -1975 patients with biopsied primary osteogenic sarcoma were treated with preoperative chemotherapy followed by surgical ablation of the primary tumor. Surgery was delayed in order to obtain a custom-fitted prosthetic bone implant in an attempt to avoid amputation. Preoperative chemotherapy included high dose methotrexate (HDMTX) with citrovorum factor rescue (CFR) and adriamycin (T-5 protocol) and was administered for 3 months preoperatively and continued with the inclusion of cyclophosphamide for approximately 5 months postoperatively. At a follow-up period of 30-52 months, 23 of 31 patients (75%) are surviving (21 of 23 with no evidence of disease). Histologic examination of primary tumor removed at surgery revealed varying degrees of tumor destruction (from very little effect to no evidence of viable tumor) attributable to the effect of chemotherapy. The 2 1 patients that are disease-free survivors had a more complete effect of preoperative chemotherapy on the primary tumor. Some patients achieving favorable effects upon the primary tumor did so only after the dose of HDMTX was escalated to greater than the starting dose of 8 g/m2. Preoperative chemotherapy for all patients with osteogenic sarcoma would seem to offer the following advantages: 1) Evaluation of the effect of HDMTX with CFR on the primary tumor with escalation of the dose of HDMTX until a clinical response is observed, thus defining the dose of HDMTX effective in that patient, to be continued postoperatively as adjuvant therapy; 2) The early use of systemic therapy to eradicate distant microfoci of disease that will eventually kill the patient if not adequately treated by effective chemotherapy; 3) Allow more time for postoperative healing without the need to start adjuvant chemotherapy immediately; and 4) Provide the surgeon time to plan resection surgery. To date, 20 additional patients with biopsy proven osteogenic sarcoma have been treated with more aggressive preoperative chemotherapy (T-7) for approximately 2 $4 months prior to definitive surgery (resection or amputation).

Clinical Value of Ezrin Expression in Primary Osteosarcoma

“…The concept of neoadjuvant chemotherapy was introduced in the late 1970s and this is now accepted as one of standard treatments for metastasis-free osteosarcoma (21,22). The advantages of neoadjuvant chemotherapy are the early treatment of potentially undetectable micrometastasis and the opportunity to assess the histologic response to neoadjuvant chemotherapy.…”

Osteosarcomas of flat bones in adolescents and adults

“…[1][2][3][4][5] In addition to prolonged adjuvant chemotherapy, most treatment programs for osteosarcoma now also incorporate preoperative (neoadjuvant) chemotherapy. Rosen et al 1,[32][33][34] were the first to advocate preoperative chemotherapy and proposed a rationale for this therapeutic approach. Also, preoperative chemotherapy provides early treatment for patients with systemic, occult micrometastases and a detailed histologic evaluation of their response to chemotherapy in the resected specimen by grading the degree of tumor necrosis.…”

“…Moreover, preoperative chemotherapy causes shrinkage of the tumor by necrosis, which makes conservative surgical resections feasible and allows time to plan definitive local therapy for primary tumors. 1,[32][33][34][35] This conservative surgery may include en bloc resection of the tumor. 32,35,36 By convention, patients with osteosarcoma of the flat bones are excluded from clinical trials of new adjuvant therapies; hence, little is known about the impact of such therapy on this subgroup of tumors.…”

Second malignant neoplasms in long‐term survivors of osteosarcoma

“…[12][13][14][15] The protocols consisted of multiagent chemotherapy and/or surgery totaling 40 weeks with some variations in the actual treatment period. Patients treated according to the T4 protocol received adjuvant chemotherapy following surgical resection of their primary tumor.…”