尤文肉瘤局部复发和远处转移的个体风险评估：多状态模型：尤文肉瘤的多状态模型。
Individual risk evaluation for local recurrence and distant metastasis in Ewing sarcoma: A multistate model: A multistate model for Ewing sarcoma.
机构信息
Department of Orthopedics, Leiden University Medical Center, Leiden, the Netherlands.
Leiden University Mathematical Institute, Leiden, the Netherlands.
出版信息
Pediatr Blood Cancer. 2019 Nov;66(11):e27943. doi: 10.1002/pbc.27943. Epub 2019 Aug 6.
BACKGROUND
We investigated the effects of surgical margins, histological response, and radiotherapy on local recurrence (LR), distant metastasis (DM), and survival in Ewing sarcoma.
PROCEDURE
Disease evolution was retrospectively studied in 982 patients with Ewing sarcoma undergoing surgery after chemotherapy using a multistate model with initial state surgery, intermediate states LR, pulmonary metastasis (DMpulm), other DM ± LR (DMother), and final state death. Effect of risk factors was estimated using Cox proportional hazard models.
RESULTS
The median follow-up was 7.6 years (95% CI, 7.2-8.0). Risk factors for LR are pelvic location, HR 2.04 (1.10-3.80), marginal/intralesional resection, HR 2.28 (1.25-4.16), and radiotherapy, HR 0.52 (0.28-0.95); for DMpulm the risk factors are <90% necrosis, HR 2.13 (1.13-4.00), and previous pulmonary metastasis, HR 4.90 (2.28-8.52); for DMother are 90% to 99% necrosis, HR 1.56 (1.09-2.23), <90% necrosis, HR 2.66 (1.87-3.79), previous bone/other metastasis, HR 3.08 (2.03-4.70); and risk factors for death without LR/DM are pulmonary metastasis, HR 8.08 (4.01-16.29), bone/other metastasis, HR 10.23 (4.90-21.36), and <90% necrosis, HR 6.35 (3.18-12.69). Early LR (0-24 months) negatively influences survival, HR 3.79 (1.34-10.76). Once DMpulm/DMother arise only previous bone/other metastasis remain prognostic for death, HR 1.74 (1.10-2.75).
CONCLUSION
Disease extent and histological response are risk factors for progression to DM or death. Tumor site and surgical margins are risk factors for LR. If disease progression occurs, previous risk factors lose their relevance. In case of isolated LR, time to recurrence is important for decision-making. Radiotherapy seems protective for LR especially in pelvic/axial. Low percentages of LR in extremity tumors and associated toxicity question the need for radiotherapy in extremity Ewing sarcoma.
背景
我们研究了手术切缘、组织学反应和放疗对尤因肉瘤局部复发（LR）、远处转移（DM）和生存的影响。
方法
采用多状态模型，对 982 例接受化疗后手术的尤因肉瘤患者的疾病进展进行回顾性研究，初始状态为手术，中间状态为 LR、肺转移（DMpulm）、其他 DM+LR（DMother）和最终状态死亡。使用 Cox 比例风险模型估计风险因素的影响。
结果
中位随访时间为 7.6 年（95%CI，7.2-8.0）。LR 的危险因素为骨盆部位，HR 为 2.04（1.10-3.80）、边缘/腔内切除术，HR 为 2.28（1.25-4.16）和放疗，HR 为 0.52（0.28-0.95）；DMpulm 的危险因素为<90%坏死，HR 为 2.13（1.13-4.00）和先前的肺转移，HR 为 4.90（2.28-8.52）；DMother 的危险因素为 90%-99%坏死，HR 为 1.56（1.09-2.23），<90%坏死，HR 为 2.66（1.87-3.79），先前的骨/其他转移，HR 为 3.08（2.03-4.70）；无 LR/DM 死亡的危险因素为肺转移，HR 为 8.08（4.01-16.29），骨/其他转移，HR 为 10.23（4.90-21.36）和<90%坏死，HR 为 6.35（3.18-12.69）。早期 LR（0-24 个月）对生存有负面影响，HR 为 3.79（1.34-10.76）。一旦发生 DMpulm/DMother，只有先前的骨/其他转移对死亡有预后意义，HR 为 1.74（1.10-2.75）。
结论
疾病程度和组织学反应是发生 DM 或死亡的危险因素。肿瘤部位和手术切缘是 LR 的危险因素。如果发生疾病进展，先前的危险因素就失去了相关性。如果出现孤立性 LR，复发时间对决策很重要。放疗对 LR 似乎有保护作用，特别是在骨盆/轴向部位。肢体肿瘤中 LR 的低发生率和相关毒性问题质疑在肢体尤因肉瘤中是否需要放疗。
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