DataSheet_1_Developing and validating a prognostic nomogram for ovarian clear cell carcinoma patients: A retrospective comparison of lymph node staging schemes with competing risk analysis.docx

PurposeLymph node (LN) involvement is a key factor in ovarian clear cell carcinoma (OCCC) although, there several indicators can be used to define prognosis. This study examines the prognostic performances of each indicator for OCCC patients by comparing the number of lymph nodes examined (TNLE), the number of positive lymph nodes (PLN), lymph node ratio (LNR), and log odds of metastatic lymph nodes (LODDS).
Methods1,300 OCCC patients who underwent lymphadenectomy between 2004 and 2015 were extracted from the Surveillance Epidemiology and End Results (SEER) database. Primary outcomes were Overall Survival (OS) and the cumulative incidence of Cancer-Specific Survival (CSS). Kaplan–Meier’s and Fine-Gray’s tests were implemented to assess OS and CSS rates. After conducting multivariate analysis, nomograms using OS and CSS were constructed based upon an improved LN system. Each nomograms’ performance was assessed using Receiver Operating Characteristics (ROC) curves, calibration curves, and the C-index which were compared to traditional cancer staging systems.
ResultsMultivariate Cox’s regression analysis was used to assess prognostic factors for OS, including age, T stage, M stage, SEER stage, and LODDS. To account for the CSS endpoint, a proportional subdistribution hazard model was implemented which suggested that the T stage, M stage, SEER stage, and LNR are all significant. This enabled us to develop a LODDS-based nomogram for OS and a LNR-based nomogram for CSS. C-indexes for both the OS and CSS nomograms were higher than the traditional American Joint Committee on Cancer (AJCC), 8th edition, staging system. Area Under the Curve (AUC) values for predicting 3- and 5-year OS and CSS between nomograms also highlighted an improvement upon the AJCC staging system. Calibration curves also performed with consistency, which was verified using a validation cohort.
ConclusionsLODDS and LNR may be better predictors than N stage, TNLE, and PLNs. For OCCC patients, both the LODDS-based and LNR-based nomograms performed better than the AJCC staging system at predicting OS and CSS. However, further large sample, real-world studies are necessary to validate the assertion.

## 研究目的
淋巴结（Lymph node, LN）受累是卵巢透明细胞癌（Ovarian clear cell carcinoma, OCCC）的关键预后影响因素，尽管目前已有多种指标可用于评估其预后。本研究旨在对比检测淋巴结数目（Total number of lymph nodes examined, TNLE）、阳性淋巴结数目（Positive lymph nodes, PLN）、淋巴结比率（Lymph node ratio, LNR）以及转移淋巴结对数优势比（Log odds of metastatic lymph nodes, LODDS）这几项指标对卵巢透明细胞癌患者的预后评估效能。

## 研究方法
本研究从监测、流行病学与最终结果（Surveillance, Epidemiology, and End Results, SEER）数据库中提取了2004至2015年间接受淋巴结清扫术的1300例卵巢透明细胞癌患者数据。主要研究终点为总生存期（Overall Survival, OS）与癌症特异性生存（Cancer-Specific Survival, CSS）的累积发生率。采用Kaplan–Meier法与Fine-Gray法分别评估总生存期与癌症特异性生存率。在完成多因素分析后，基于优化的淋巴结分期系统构建了总生存期与癌症特异性生存列线图。通过受试者工作特征（Receiver Operating Characteristics, ROC）曲线、校准曲线以及C指数对每一列线图的性能进行评估，并与传统癌症分期系统进行对比。

## 研究结果
采用多因素Cox回归分析评估总生存期的预后影响因素，结果显示年龄、T分期、M分期、SEER分期以及LODDS均具有统计学意义。针对癌症特异性生存终点，采用比例子分布风险模型分析，结果提示T分期、M分期、SEER分期以及LNR均为显著预后因素。基于上述结果，我们分别构建了基于LODDS的总生存期列线图以及基于LNR的癌症特异性生存列线图。本研究构建的总生存期与癌症特异性生存列线图的C指数均高于第8版美国癌症联合委员会（American Joint Committee on Cancer, AJCC）分期系统。列线图预测3年及5年总生存期与癌症特异性生存的曲线下面积（Area Under the Curve, AUC）同样显示其性能优于AJCC分期系统。校准曲线的拟合度良好，该结果通过验证队列得到了验证。

## 研究结论
LODDS与LNR或许是优于N分期、检测淋巴结数目以及阳性淋巴结数目的预后预测指标。对于卵巢透明细胞癌患者，基于LODDS与LNR构建的列线图在预测总生存期与癌症特异性生存方面均优于AJCC分期系统。然而，仍需开展更大样本量的真实世界研究以验证本研究结论。