[肢体局限性骨肉瘤的新辅助治疗。来自骨肉瘤协作研究组COSS的925例患者的结果]

[Neoadjuvant therapy for localized osteosarcoma of extremities. Results from the Cooperative osteosarcoma study group COSS of 925 patients].

作者信息

Bielack S, Kempf-Bielack B, Schwenzer D, Birkfellner T, Delling G, Ewerbeck V, Exner G U, Fuchs N, Göbel U, Graf N, Heise U, Helmke K, von Hochstetter A R, Jürgens H, Maas R, Münchow N, Salzer-Kuntschik M, Treuner J, Veltmann U, Werner M, Winkelmann W, Zoubek A, Kotz R

机构信息

Universitäts-Kinderklinik, Pädiatrische Hämatologie/Onkologie, Westfälische Wilhelms-Universität Münster.

出版信息

Klin Padiatr. 1999 Jul-Aug;211(4):260-70. doi: 10.1055/s-2008-1043798.

DOI:10.1055/s-2008-1043798

PMID:10472560

Abstract

BACKGROUND

Owing to twenty years of multicentric interdisciplinary cooperation, the COSS group has been able to collect data on a large group of osteosarcoma patients treated by neoadjuvant therapy. This paper reviews results achieved in patients with localized extremity tumors.

INCLUSION CRITERIA

Registration into a completed neoadjuvant COSS-Study. Histologically confirmed, primary, localized, high-grade, central osteosarcoma of an extremity; age < 40 years; no pretreatment; interval diagnosis to chemotherapy < or = 3 weeks; no severe comorbidity. Chemotherapy: HD-methotrexate +/- doxorubicin +/- cisplatin +/- ifosfamide +/- BCD. Scheduled local therapy: Surgery.

RESULTS

925 evaluable patients from 101 institutions. Median age 15 years, m:f 1.4:1. Primary site: femur 510, tibia 251, humerus 100, fibula 51, other 13. Tumor-size < 1/3 of the involved bone 616, > or = 1/3 304. Definitive surgery in 903/925 cases, 443 limb salvage procedures. Good response (> 90% necrosis) in 469/806 (58.2%) evaluated tumors. Median follow-up for surviving patients: 5.42 years. Actuarial survival after 5 and 10 years: 72.5% (95%-CI 69.3-75.7) and 66.3% (62.5-70.0), relapse-free 62.1% (58.7-65.4) and 59.4% (55.8-63.0). 683/925 alive (601 first remission), 242 deceased (212 tumor progression, 30 other causes). 66.2% (97.3%) of all relapses within 2 (5) years. Prognosis correlates with tumor-size (< vs. > or = 1/3: 69.9% vs. 58.3% at 10 years) and -site (tibia: 74.2%, humerus: 54.5%) and -response (good vs. poor: 78.2% vs. 52.5%) (all p < 0.01). Actuarial 10-year survival by response grading I-VI according to Salzer-Kuntschik 80.9%, 82.8%, 71.1%, 60.7%, 47.7%, 27.3%. COSS-studies with preoperative 4-drug therapy more efficacious than less aggressive protocols. No impact of doxorubicin scheduling (sequential: rapid vs. 48 h-continuous infusion) or cisplatin scheduling (randomized: 5 h vs. 72 h-infusion) on prognosis detected.

CONCLUSIONS

Intensive multiagent chemotherapy and delayed surgery for localized extremity osteosarcoma led to excellent oncologic results in the COSS-studies. Tumor-size, -site, and -response as well as the intensity of upfront chemotherapy correlated with outcome. Giving doxorubicin and cisplatin by continuous infusions did not result in discernible prognostic disadvantages.

摘要

背景

经过20年的多中心跨学科合作，COSS研究组得以收集大量接受新辅助治疗的骨肉瘤患者的数据。本文回顾了局限性肢体肿瘤患者所取得的治疗结果。

纳入标准

登记进入一项已完成的新辅助COSS研究。组织学确诊为肢体原发性、局限性、高级别、中央型骨肉瘤；年龄<40岁；未接受过预处理；从诊断到化疗的间隔时间≤3周；无严重合并症。化疗方案：大剂量甲氨蝶呤±阿霉素±顺铂±异环磷酰胺±BCD。预定的局部治疗：手术。

结果

来自101个机构的925例可评估患者。中位年龄15岁，男女比例为1.4:1。原发部位：股骨510例，胫骨251例，肱骨100例，腓骨51例，其他部位13例。肿瘤大小<受累骨的1/3者616例，≥1/3者304例。925例中有903例行根治性手术，443例为保肢手术。806例评估肿瘤中469例（58.2%）反应良好（坏死>90%）。存活患者的中位随访时间为5.42年。5年和10年的精算生存率分别为72.5%（95%可信区间69.3 - 75.7）和66.3%（62.5 - 70.0），无复发生存率分别为62.1%（58.7 - 65.4）和59.4%（55.8 - 63.0）。925例中有683例存活（601例首次缓解），242例死亡（212例肿瘤进展，30例因其他原因）。所有复发的66.2%（97.3%）发生在2（5）年内。预后与肿瘤大小（<1/3与≥1/3：10年时分别为69.9%与58.3%）、部位（胫骨：74.2%，肱骨：54.5%）和反应（良好与差：78.2%与52.5%）相关（均p<0.01）。根据Salzer - Kuntschik反应分级I - VI的10年精算生存率分别为80.9%、82.8%、71.1%、60.7%、47.7%、27.3%。术前采用4种药物治疗的COSS研究比采用不太积极方案的研究更有效。未检测到阿霉素给药方案（序贯：快速与48小时持续输注）或顺铂给药方案（随机：5小时与72小时输注）对预后有影响。