Forsberg Jonathan A, Wedin Rikard, Boland Patrick J, Healey John H
Regenerative Medicine, Naval Medical Research Center, 503 Robert Grant Avenue, Silver Spring, MD, 20910, USA.
Uniformed Services University-Walter Reed Department of Surgery, Bethesda, MD, USA.
Clin Orthop Relat Res. 2017 Apr;475(4):1252-1261. doi: 10.1007/s11999-016-5187-3. Epub 2016 Dec 1.
Objective means of estimating survival can be used to guide surgical decision-making and to risk-stratify patients for clinical trials. Although a free, online tool ( www.pathfx.org ) can estimate 3- and 12-month survival, recent work, including a survey of the Musculoskeletal Tumor Society, indicated that estimates at 1 and 6 months after surgery also would be helpful. Longer estimates help justify the need for more durable and expensive reconstructive options, and very short estimates could help identify those who will not survive 1 month and should not undergo surgery. Thereby, an important use of this tool would be to help avoid unsuccessful and expensive surgery during the last month of life.
QUESTIONS/PURPOSES: We seek to provide a reliable, objective means of estimating survival in patients with metastatic bone disease. After generating models to derive 1- and 6-month survival estimates, we determined suitability for clinical use by applying receiver operator characteristic (ROC) (area under the curve [AUC] > 0.7) and decision curve analysis (DCA), which determines whether using PATHFx can improve outcomes, but also discerns in which kinds of patients PATHFx should not be used.
We used two, existing, skeletal metastasis registries chosen for their quality and availability. Data from Memorial Sloan-Kettering Cancer Center (training set, n = 189) was used to develop two Bayesian Belief Networks trained to estimate the likelihood of survival at 1 and 6 months after surgery. Next, data from eight major referral centers across Scandinavia (n = 815) served as the external validation set-that is, as a means to test model performance in a different patient population. The diversity of the data between the training set from Memorial Sloan-Kettering Cancer Center and the Scandinavian external validation set is important to help ensure the models are applicable to patients in various settings with differing demographics and treatment philosophies. We considered disease-specific, laboratory, and demographic information, and the surgeon's estimate of survival. For each model, we calculated the area under the ROC curve (AUC) as a metric of discriminatory ability and the Net Benefit using DCA to determine whether the models were suitable for clinical use.
On external validation, the AUC for the 1- and 6-month models were 0.76 (95% CI, 0.72-0.80) and 0.76 (95% CI, 0.73-0.79), respectively. The models conferred a positive net benefit on DCA, indicating each could be used rather than assume all patients or no patients would survive greater than 1 or 6 months, respectively.
Decision analysis confirms that the 1- and 6-month Bayesian models are suitable for clinical use.
These data support upgrading www.pathfx.org with the algorithms described above, which is designed to guide surgical decision-making, and function as a risk stratification method in support of clinical trials. This updating has been done, so now surgeons may use any web browser to generate survival estimates at 1, 3, 6, and 12 months after surgery, at no cost. Just as short estimates of survival help justify palliative therapy or less-invasive approaches to stabilization, more favorable survival estimates at 6 or 12 months are used to justify more durable, complicated, and expensive reconstructive options.
客观的生存评估方法可用于指导手术决策,并对患者进行风险分层以开展临床试验。尽管有一个免费的在线工具(www.pathfx.org)可以估算3个月和12个月的生存率,但最近的研究工作,包括对肌肉骨骼肿瘤学会的一项调查表明,术后1个月和6个月的生存率估算也会有所帮助。更长时间的生存率估算有助于证明采用更持久且昂贵的重建方案的必要性,而非常短的生存率估算则有助于识别那些生存期不足1个月且不应接受手术的患者。因此,该工具的一个重要用途是帮助避免在生命的最后一个月进行不成功且昂贵的手术。
问题/目的:我们旨在提供一种可靠、客观的方法来估算转移性骨病患者的生存率。在生成用于推导1个月和6个月生存率估算的模型后,我们通过应用受试者工作特征(ROC)(曲线下面积[AUC]>0.7)和决策曲线分析(DCA)来确定其临床适用性,决策曲线分析不仅能确定使用PATHFx是否能改善预后,还能辨别哪些患者不适合使用PATHFx。
我们使用了两个现有的骨骼转移瘤登记处,因其质量和数据可得性而被选中。来自纪念斯隆凯特琳癌症中心的数据(训练集,n = 189)用于开发两个贝叶斯信念网络,训练这些网络以估算术后1个月和6个月的生存可能性。接下来,来自斯堪的纳维亚半岛八个主要转诊中心的数据(n = 815)用作外部验证集,即作为在不同患者群体中测试模型性能的一种手段。纪念斯隆凯特琳癌症中心的训练集与斯堪的纳维亚半岛外部验证集之间的数据多样性对于确保模型适用于具有不同人口统计学特征和治疗理念的各种患者群体非常重要。我们考虑了疾病特异性、实验室和人口统计学信息,以及外科医生对生存率的估计。对于每个模型,我们计算ROC曲线下面积(AUC)作为区分能力的指标,并使用DCA计算净效益,以确定模型是否适合临床使用。
在外部验证中,1个月和6个月模型的AUC分别为0.76(95%CI,0.72 - 0.80)和0.76(95%CI,0.73 - 0.79)。这些模型在DCA上显示出正净效益,表明可以使用每个模型,而不是假设所有患者或没有患者分别能存活超过1个月或6个月。
决策分析证实1个月和6个月的贝叶斯模型适用于临床使用。