目的:骨肉瘤的预后因素已得到很好的描述,但是缺乏评估长期幸存者进一步发展过程的分析。我们使用合作骨肉瘤研究组(COSS)的大型数据库进行了此类分析。
方法:在1980-04/2019年的COSS数据库中搜索了四肢或躯干原发性高级别中央骨肉瘤的5年幸存者。对确定的患者进行了进一步的生存结果分析,评估在最初的疾病表现和治疗中已经明显的潜在预后和预测因素,以及在随访的前5年中的病程。
结果:确定了2,000和9名以前符合条件的患者(初始诊断时的中位年龄15.1(2.5-63.0)岁;男性与女性1149(57.2%)860(42.8%);四肢与后备箱1927年(95.9%)与82(4.1%);四肢原发性<1/3vs.≥1/3受累骨997(67.8%)与474(32.2%)(456个未知);局部与原发性转移1881(93.6%)与128(6.4%);骨肉瘤为继发性恶性肿瘤41/2009(2.0%)。从化疗开始的治疗与初次手术相比,1860(92.6%)与149(7.4%);通过肢体挽救与消融进行的确定性肿瘤手术1347(67.0%)与659(1不手术,2未知);1765例(94.9%)接受新辅助化疗的患者对术前化疗的肿瘤反应,良好(<10%的存活肿瘤)与较差的1130(64.0%)与635(36.0%),记录了19例(0.9%)肿瘤的局部放疗。前5年的复发率是否,1681年(83.7%)和328年(16.3%)。初始诊断后5年开始的中位随访6.1(0.002-32.2)年;1815名幸存者和194例死亡。所有患者再过5/10/15/20年后的总生存率为91.7%/88.9%/85.8%/83.4%;缓解1-5年为97.5%/95.2%/92.4%/89.9%,复发1-5年为62.7%/57.3%/53.0%/51.2%(p<0.001)。诊断时所有患者年龄的重要生存率预测因素(p=0.038),肿瘤部位(p=0.030),经历过骨肉瘤为继发性恶性肿瘤(p<0.001),肿瘤对术前化疗的反应(p=0.002)。多变量Cox回归测试可用于1759(87.6%)具有完整数据集的患者:在1-5年复发(p<0.001),诊断时年龄较大(p=0.009),骨肉瘤作为继发性恶性肿瘤(p=0.013)保持显著性。
结论:非常重要的死亡预测因子,如肿瘤对化疗的反应程度,在5年生存后不再有效。恶性肿瘤的个体病史及其结果似乎至关重要。
结论:该基准分析明确定义了骨肉瘤5年存活者进一步病程的危险因素。它主张大型面向疾病的数据库以及很长的随访期。新的发现很可能需要创新的统计模型来分析此类队列。
OBJECTIVE: Prognostic factors have been well described for osteosarcoma, but analyses evaluating the further course of long-term survivors are lacking. We used the large database of the Cooperative Osteosarcoma Study Group (COSS) to perform such an analysis.
METHODS: The COSS database 1980-04/2019 was searched for 5-year survivors of primary high-grade central osteosarcoma of the
extremities or trunk. Identified patients were analyzed for their further survival outcomes, assessing potentially prognostic and predictive factors already evident at initial disease presentation and treatment as well as their disease course during the first 5 years of follow-up.
RESULTS: Two thousand and nine former eligible patients were identified (median age at initial diagnosis 15.1 (2.5-63.0) years; male vs. female 1149 (57.2%) vs. 860 (42.8%);
extremities vs. trunk 1927 (95.9%) vs. 82 (4.1%); extremity primaries <1/3 vs. ≥1/3 of the involved bone 997 (67.8%) vs. 474 (32.2%) (456 unknown); localized vs. primary metastatic 1881 (93.6%) vs. 128 (6.4%); osteosarcoma as a secondary malignancy 41/2009 (2.0%)). Therapy starting by chemotherapy versus primary surgery 1860 (92.6%) versus 149 (7.4%); definitive tumor surgery by limb salvage versus ablative 1347 (67.0%) versus 659 (1 no surgery, 2 unknown); tumor response to preoperative chemotherapy documented for 1765 (94.9%) patients receiving neoadjuvant chemotherapy, good (<10% viable tumor) versus poor 1130 (64.0%) versus 635 (36.0%), local radiotherapy documented for 19 (0.9%) tumors. Recurrence during preceding 5 years no versus yes 1681 (83.7%) versus 328 (16.3%). Median follow-up starting 5 years after initial diagnosis 6.1 (0.002-32.2) years; 1815 survivors and 194 deaths. Overall survival after another 5/10/15/20 years 91.7%/88.9%/85.8%/83.4% for all patients; 97.5%/95.2%/92.4%/89.9% if in remission years 1-5 versus 62.7%/57.3%/53.0%/51.2% if recurrence year 1-5 (p < 0.001). Significant predictors of survival for all patients age at diagnosis (p = 0.038), tumor site (p = 0.030), having experienced the osteosarcoma as secondary malignancy (p < 0.001), tumor response to preoperative chemotherapy (p = 0.002). Multivariate Cox regression testing possible for 1759 (87.6%) patients with complete dataset: Having had a recurrence in years 1-5 (p < 0.001), older age at diagnosis (p = 0.009), and osteosarcoma as secondary malignancy (p = 0.013) retained significance.
CONCLUSIONS: Highly important predictors of death such as the extent of tumor response to chemotherapy no longer remain valid after 5-year survival. The individual history of malignancies and their outcomes seems to gain pivotal importance.
CONCLUSIONS: This benchmark analysis clearly defined risk factors for the further course of 5-year survivors from osteosarcoma. It argues for large disease-oriented databases as well as for very long follow-up periods. Novel findings will most likely require innovative statistical models to analyze such cohorts.