Bacci G, Picci P, Briccoli A, Avella M, Ferrari S, Femino F P, Monti C, Ruggieri P, Rizzente A G, Casadei R
Sezione Chemioterapia Tumori Ossei, Istituto Ortopedico Rizzoli, Bologna, Italy.
Tumori. 1992 Jun 30;78(3):200-6. doi: 10.1177/030089169207800311.
From September 1986 to December 1989, 26 selected patients with high-grade osteosarcoma of the extremities metastatic at presentation were treated with primary chemotherapy (high doses of methotrexate, -cisplatinum and adriamycin) followed by surgery. Twenty-one cases underwent resections of the primary and metastatic tumor at the same time; owing to the disappearance of lung metastases after preoperative chemotherapy in 3 cases, only the primary tumor was operated on. Due to progression of the disease in 2 patients, no surgery was performed. Histologic examination of the resected specimen was performed to evaluate the percentage of necrosis produced by chemotherapy on the primary and metastatic tumor. After surgery, the patients received further chemotherapy with the same drugs used preoperatively plus ifosfamide and VP-16. The histologic response of the primary tumor was good (> 90% tumor necrosis) in 25% of the cases; in the resected metastatic nodules, 23% had good responses. A discrepancy between the histologic response of the primary and secondary tumor was observed in only 15% of the cases. These results seem to confirm the validity of the strategy (widely used today in the neoadjuvant treatment of non-metastatic osteosarcoma) of changing the postoperative treatment when the histologic response of the primary tumor is poor. At an average follow-up of 3.5 years, only 6 patients remained disease-free; 19 patients relapsed and 1 patient died for adriamycin cardiotoxicity. Of the 19 relapsed patients, 16 died and 3 are still alive but with uncontrolled disease. These results are much worse than those obtained in 144 cases of non-metastatic osteosarcoma of the extremities treated in the same period with the same preoperative chemotherapy (77% with good response in the primary tumor and 78% with continuous disease-free survival). The data suggest that a very effective neoadjuvant chemotherapy for nonmetastatic osteosarcoma of the extremities gives disappointing results in osteosarcoma of the extremities which is metastatic at presentation.
1986年9月至1989年12月，对26例初诊时已发生远处转移的四肢高级别骨肉瘤患者采用了术前化疗（大剂量甲氨蝶呤、顺铂和阿霉素）加手术治疗。21例患者同时切除了原发肿瘤和转移瘤；3例患者术前化疗后肺转移灶消失，仅对原发肿瘤进行了手术。2例患者因病情进展未行手术。对切除标本进行组织学检查，以评估化疗对原发肿瘤和转移瘤产生的坏死百分比。术后，患者接受了与术前相同的药物加异环磷酰胺和依托泊苷的进一步化疗。25%的病例中，原发肿瘤的组织学反应良好（肿瘤坏死>90%）；在切除的转移结节中，23%反应良好。仅15%的病例中观察到原发肿瘤和继发肿瘤的组织学反应存在差异。这些结果似乎证实了在原发肿瘤组织学反应较差时改变术后治疗策略（如今广泛用于非转移性骨肉瘤的新辅助治疗）的有效性。平均随访3.5年时，仅6例患者无病生存；19例患者复发，1例患者因阿霉素心脏毒性死亡。19例复发患者中，16例死亡，3例仍存活但病情未得到控制。这些结果比同期采用相同术前化疗治疗的144例四肢非转移性骨肉瘤患者的结果差得多（原发肿瘤反应良好率为77%，持续无病生存率为78%）。数据表明，一种对四肢非转移性骨肉瘤非常有效的新辅助化疗，对初诊时已发生转移的四肢骨肉瘤却产生了令人失望的结果。
