Prognostic Models and Signatures in Retroperitoneal Sarcoma

CINSARC (the Complexity Index in SARComas) is a transcriptomic profile that independently forecasts the risk of metastasis in soft tissue sarcoma patients. This study aimed to (1) deliver the first standalone validation of CINSARC in a group of patients with retroperitoneal sarcoma (RPS) and (2) investigate if integrating CINSARC could improve the predictive accuracy of the Sarculator model. Overall design: The Istituto Nazionale Tumori (INT) group comprised patients with primary localized retroperitoneal sarcoma (RPS) who underwent curative surgery between 2011 and 2015, as part of the SARCOMICS study. Patients were divided into two categories based on their CINSARC status: low-risk (C1) and high-risk (C2). The main outcomes measured were overall survival (OS) and disease-free survival (DFS), with multivariable Cox models used for analysis. The accuracy of the Sarculator was evaluated based on its discriminatory power (using Harrell's C-index) and calibration (assessed via calibration plots and the Brier score), both before and after incorporating CINSARC data. The study confirmed that CINSARC serves as a prognostic marker for OS and DFS in patients with primary RPS who received surgical treatment. However, adding CINSARC to the Sarculator did not enhance its discrimination or calibration, indicating that its integration may not offer additional clinical advantages.

CINSARC（肉瘤复杂性指数，Complexity Index in SARComas）是一种转录组谱（transcriptomic profile），可独立预测软组织肉瘤患者的转移风险。本研究旨在实现两大目标：（1）在腹膜后肉瘤（retroperitoneal sarcoma, RPS）患者队列中首次完成CINSARC的独立验证；（2）探究整合CINSARC能否提升Sarculator模型（Sarculator model）的预测精度。总体研究设计：本研究队列隶属于SARCOMICS研究，由意大利国家肿瘤研究所（Istituto Nazionale Tumori, INT）牵头纳入受试者，包含2011至2015年间接受根治性手术的原发性局限性腹膜后肉瘤（RPS）患者。研究人员依据CINSARC状态将患者划分为低危组（C1）与高危组（C2）。本研究的主要终点为总生存期（overall survival, OS）与无病生存期（disease-free survival, DFS），数据分析采用多变量Cox比例风险模型。在整合CINSARC数据前后，分别通过区分度（采用Harrell一致性指数（Harrell's C-index））与校准度（通过校准曲线、Brier评分（Brier score）评估）来评价Sarculator模型的预测性能。本研究证实，CINSARC可作为接受手术治疗的原发性RPS患者总生存期与无病生存期的预后标志物。然而，将CINSARC整合至Sarculator模型后，并未提升其区分度与校准度，提示该整合策略或无法为临床诊疗带来额外获益。