Primary chemotherapy and delayed surgery (neoadjuvant chemotherapy) for osteosarcoma of the extremities the istituto rizzoli experience in 127 patients treated preoperatively with intravenous methotrexate (high versus moderate doses) and intraarterial cisplatin

Abstract

patients with localized osteosarcoma of the extremity were treated with neoadjuvant chemotherapy. Preoperative chemotherapy consisted of two cycles of methotrexate (MTX) (high or moderate doses) followed by 6 days by cisplatin (CDP). Surgery was an amputation or a rotation plasty, or a limb salvage. Necrosis was good in 52% of cases, fair in 36%, and poor in 12%. Postoperative chemotherapy consisted of Adriamycin (doxorubicin [ADM]) and bleomycin (BCD) for poor responders; and ADM, MTX, and CDP for fair responders. Good responders were treated as fair responders or with only MTX and CDP. At a 47-month follow-up, 66 patients remained continuously disease free and 61 patients developed metastases. Six of these patients had also a local recurrence. According to the grade of necrosis, the cumulative disease-free probability at 5 years was 67% for good responders, 42% for fair responders, and for poor responders 10% at 45 months. According to the doses of MTX, survival at 5 years was 58% for patients who received high doses and 42% for patients treated with moderate doses. No differences in the rate of survivors were observed between amputated patients and patients treated with limb salvage. The authors conclude that (1) a limb salvage procedure is possible in about 70% of cases and as safe as demolitive surgery, if adequate surgical margins are achieved; (2) good responders have a better prognosis than fair and poor responders if postoperative chemotherapy is sufficiently prolonged and also includes ADM; (3) a different postoperative chemotherapy for poor responders did not improve their prognosis: and (4) a multidrug regimen using high doses of MTX is probably more effective than moderate doses.

Molecular characterization of the response to chemotherapy in conventional osteosarcomas: Predictive value of HSD17B10 and IFITM2

“…Adjuvant and neoadjuvant chemotherapy have significantly improved the long-term survival rate for patients with osteosarcoma. [1][2][3] Nevertheless, recurrent disease still occurs in about 30-40% of patients and more than 70% of them die of their tumor, despite second-line treatment.…”

“…1,[7][8][9][10] Intensified first-line chemotherapy regimens could improve prognosis, but the risk is over-treatment of patients who could benefit from less aggressive regimens. 1,[7][8][9][10] No survival benefit has been convincingly shown through the administration of more intensified therapy to poor responders. This suggests that there may be an innate biological difference between good responsive and poor responsive tumors.…”

Clinical Characteristics and Treatment Results of Pediatric Osteosarcoma: The Role of High Dose Chemotherapy with Autologous Stem Cell Transplantation

“…The long term survival rate was less than 20% when patients received surgery only (1), but the survival rate reached 50∼70% after the introduction of chemotherapy in the 1970s (2)(3)(4)(5). Particularly, by the administration of neoadjuvant chemotherapy, limb salvage surgery became feasible, and the response to neoadjuvant chemotherapy was able to be used as a good marker to predict the long term survival rate (6,7).…”

“…In the past, when surgery was the only treatment, most patients showed relapse after amputation, and the 5-year survival rate was less than 10% (1). With the introduction of neoadjuvant chemotherapy, the 5-year survival increased up to 70% and limb-salvage operation became possible improving the quality of life (2)(3)(4)(5). However, treatment outcomes are still poor in cases of relapse or refractory osteosarcoma or cases showing metastasis at the time of diagnosis.…”

Relation between cellular doxorubicin binding ability to nuclear DNA and histologic response to preoperative chemotherapy in patients with osteosarcoma

“…A lthough chemosensitivity is the most important prognostic factor in human osteosarcoma, [1][2][3][4] there are no clinically useful chemosensitivity tests for osteosarcoma. 5,6 Therefore, development of a new chemosensitivity test for osteosarcoma is an urgent concern.…”