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四肢骨转移手术治疗后生存预测的 SPRING 模型的外部验证和优化。

External Validation and Optimization of the SPRING Model for Prediction of Survival After Surgical Treatment of Bone Metastases of the Extremities.

机构信息

M. S. Sørensen, M. M. Petersen, Musculoskeletal Tumor Section, Department of Orthopaedic Surgery, University Hospital Rigshospitalet, University of Copenhagen, Copenhagen, Denmark T. A. Gerds, Section of Biostatistics, University of Copenhagen, Copenhagen, Denmark K. Hindsø, Department of Orthopaedic Surgery, University Hospital Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.

出版信息

Clin Orthop Relat Res. 2018 Aug;476(8):1591-1599. doi: 10.1097/01.blo.0000534678.44152.ee.

Abstract

BACKGROUND

Survival predictions before surgery for metastatic bone disease in the extremities (based on statistical models and data of previous patients) are important for choosing an implant that will function for the remainder of the patient's life. The 2008-SPRING model, presented in 2016, enables the clinician to predict expected survival before surgery for metastatic bone disease in the extremities. However, to maximize the model's accuracy, it is necessary to maintain and update the patient database to refit the prediction models achieving more accurate calibration.

QUESTIONS/PURPOSES: The purposes of this study were (1) to refit the 2008-SPRING model for prediction of survival before surgery for metastatic bone disease in the extremities with a more modern cohort; and (2) to evaluate the performance of the refitted SPRING model in a population-based cohort of patients having surgery for metastatic bone disease in the extremities.

METHODS

We produced the 2013-SPRING model by adding to the 2008-SPRING model (n = 130) a cohort of patients from a consecutive institutional database of patients who underwent surgery for bone metastases in the extremities with bone resection and reconstruction between 2009 and 2013 at a highly specialized surgical center in Denmark (n = 140). Currently the model is only available as the nomogram fully available in the current article, which is sufficient to use in daily clinical work, but we are working on making the tool available online. As such, the 2013-SPRING model was produced using a consecutive cohort of patients (n = 270) treated during an 11-year period (2003-2013) called the training cohort, all treated with bone resection and reconstruction. We externally validated the 2008-SPRING and the 2013-SPRING models in a prospective cohort (n = 164) of patients who underwent surgery for metastatic bone disease in the extremities from May 2014 to May 2016, called the validation cohort. The validation cohort was identified from a cross-section of the Danish population who were treated for metastatic lesions (using endoprostheses and internal fixation) in the extremities at five secondary surgical centers and one highly specialized surgical center. This cross-section is representative of the Danish population and no patients were treated outside the included centers as a result of public healthcare settings. The indications for surgery for training and the validation cohort were pathologic fracture, impending fracture, or intractable pain despite radiation. Exact date of death was known for all patients as a result of the Danish Civil Registration System and no loss to followup existed. In the training cohort, 150 patients (out of 270 [56%]) and in the validation cohort 97 patients (out of 164 [59%]) died of disease within 1 year postoperatively. The 2013 model did not differ from the 2008 model and included hemoglobin, complete fracture/impending fracture, visceral and multiple bone metastases, Karnofsky Performance Status, and the American Society of Anesthesiologists score and primary cancer. The models were evaluated by area under the receiver operating characteristic curve (AUC ROC) and Brier score (the lower the better).

RESULTS

The 2013-SPRING model was successfully refitted with a cohort using more patients than the 2008-SPRING model. Comparison of performance in external validation between the 2008 and 2013-SPRING models showed the AUC ROC was increased by 3% (95% confidence interval [CI], 0%-5%; p = 0.027) and 2% (95% CI, 0%-4%; p = 0.013) at 3-month and 6-month survival predictions, respectively, but not at 12 months at 1% (95% CI, 0%-3%; p = 0.112). Brier score was improved by -0.018 (95% CI, -0.032 to -0.004; p = 0.011) for 3-month, -0.028 (95% CI, -0.043 to -0.0123; p < 0.001) for 6-month, and -0.014 (95% CI, -0.025 to -0.002; p = 0.017) for 12-month survival prediction.

CONCLUSIONS

We improved the SPRING model's ability to predict survival after surgery for metastatic bone disease in the extremities. As such, the refitted 2013-SPRING model gives the surgeon a tool to assist in the decision-making of a surgical implant that will serve the patient for the remainder of their life. The 2013-SPRING model may provide increased quality of life for patients with bone metastasis because potential implant failures can be minimized by precise survival prediction preoperatively and the model is freely available and ready to use from the current article.

LEVEL OF EVIDENCE

Level I, diagnostic study.

摘要

背景

在四肢转移性骨病的手术前,对基于既往患者的统计模型和数据的生存预测非常重要,这有助于选择可在患者余生中发挥作用的植入物。2016 年提出的 2008-SPRING 模型可用于预测四肢转移性骨病患者手术前的预期生存时间。然而,为了最大限度地提高模型的准确性,有必要维护和更新患者数据库,重新拟合预测模型,以实现更精确的校准。

问题/目的:本研究的目的是:(1)使用更现代的队列重新拟合 2008-SPRING 模型,以预测四肢转移性骨病患者手术前的生存时间;(2)评估经过改良的 SPRING 模型在一个基于人群的接受四肢转移性骨病手术的患者队列中的表现。

方法

我们通过在一个连续的机构数据库中添加患者(n = 130),从而产生了 2013-SPRING 模型。该数据库包含了 2009 年至 2013 年在丹麦一家高度专业化的外科中心接受四肢骨转移切除术和重建的患者。目前,该模型仅作为当前文章中提供的完整诺模图,足以在日常临床工作中使用,但我们正在努力使其在线可用。因此,2013-SPRING 模型是使用一个连续的患者队列(n = 270)在 11 年期间(2003-2013 年)产生的,称为训练队列,所有患者均接受骨切除术和重建。我们在一个前瞻性队列(n = 164)中对外验证了 2008-SPRING 和 2013-SPRING 模型,该队列于 2014 年 5 月至 2016 年 5 月接受了四肢转移性骨病手术,称为验证队列。该验证队列是从丹麦人群中随机选择的,他们在五个二级外科中心和一个高度专业化的外科中心接受了四肢转移性病变(使用假体和内固定)的治疗。这一分层代表了丹麦人群,由于公共医疗保健设置,没有患者在纳入中心之外接受治疗。训练队列和验证队列中手术的适应证为病理性骨折、即将发生的骨折或尽管进行了放射治疗仍无法控制的疼痛。由于丹麦民事登记系统,所有患者的确切死亡日期均可得知,并且不存在随访丢失的情况。在训练队列中,150 名患者(270 名患者中的 56%)和验证队列中 97 名患者(164 名患者中的 59%)在术后 1 年内死于疾病。2013 年的模型与 2008 年的模型没有差异,包括血红蛋白、完全骨折/即将发生的骨折、内脏和多发性骨转移、卡诺夫斯基绩效状态和美国麻醉师协会评分以及原发性癌症。通过接受者操作特征曲线(ROC)下面积(AUC ROC)和 Brier 评分(分数越低越好)评估模型。

结果

该 2013-SPRING 模型使用比 2008-SPRING 模型更多的患者成功进行了拟合。对外验证 2008 年和 2013 年 SPRING 模型的性能比较显示,AUC ROC 在 3 个月和 6 个月的生存预测中分别提高了 3%(95%置信区间,0%-5%;p = 0.027)和 2%(95%置信区间,0%-4%;p = 0.013),而在 12 个月时为 1%(95%置信区间,0%-3%;p = 0.112)。Brier 评分在 3 个月时降低了 0.018(95%置信区间,0.032 至 0.004;p = 0.011),在 6 个月时降低了 0.028(95%置信区间,0.043 至 0.0123;p < 0.001),在 12 个月时降低了 0.014(95%置信区间,0.025 至 0.002;p = 0.017)。

结论

我们提高了 SPRING 模型预测四肢转移性骨病患者手术后生存时间的能力。因此,经过改良的 2013-SPRING 模型为外科医生提供了一种工具,帮助他们在决定使用哪种外科植入物时做出决策,这种植入物将在患者的余生中为其服务。由于可以通过术前精确的生存预测来最小化潜在的植入物失败的风险,因此 2013-SPRING 模型可能会为患有骨转移的患者提供更高的生活质量,而且该模型是免费提供的,并且可以从当前文章中立即使用。

证据水平

I 级,诊断研究。

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