Department of Surgery and Transplantation, University Hospital of Zurich, Zurich, Switzerland.
Department of Surgery, Cantonal Hospital of St. Gallen, St. Gallen, Switzerland.
Ann Surg. 2018 Nov;268(5):845-853. doi: 10.1097/SLA.0000000000002899.
Adequate selection of patients with peritoneal metastasis (PM) for cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) remains critical for successful long-term outcomes. Factors reflecting tumor biology are currently poorly represented in the selection process. The prognostic relevance of RAS/RAF mutations in patients with PM remains unclear.
Survival data of patients with colorectal PM operated in 6 European tertiary centers were retrospectively collected and predictive factors for survival identified by Cox regression analyses. A simple point-based risk score was developed to allow patient selection and outcome prediction.
Data of 524 patients with a median age of 59 years and a median peritoneal cancer index of 7 (interquartile range: 3-12) were collected. A complete resection was possible in 505 patients; overall morbidity and 90-day mortality were 50.9% and 2.1%, respectively. PCI [hazard ratio (HR): 1.08], N1 stage (HR: 2.15), N2 stage (HR: 2.57), G3 stage (HR: 1.80) as well as KRAS (HR: 1.46) and BRAF (HR: 3.97) mutations were found to significantly impair survival after CRS/HIPEC on multivariate analyses. Mutations of RAS/RAF impaired survival independently of targeted treatment against EGFR. Consequently, a simple point-based risk score termed BIOSCOPE (BIOlogical Score of COlorectal PEritoneal metastasis) based on PCI, N-, G-, and RAS/RAF status was developed, which showed good discrimination [development area under the curve (AUC) = 0.72, validation AUC = 0.70], calibration (P = 0.401) and allowed categorization of patients into 4 groups with strongly divergent survival outcomes.
RAS/RAF mutations impair survival after CRS/HIPEC. The novel BIOSCOPE score reflects tumor biology, adequately stratifies long-term outcomes, and improves patient assessment and selection.
对于接受细胞减灭术（CRS）和腹腔热灌注化疗（HIPEC）的腹膜转移（PM）患者，充分选择仍然是获得成功长期预后的关键。反映肿瘤生物学的因素在选择过程中目前代表不足。RAS/RAF 突变在 PM 患者中的预后相关性仍不清楚。
回顾性收集了在 6 个欧洲三级中心接受结直肠 PM 手术的患者的生存数据，并通过 Cox 回归分析确定了生存的预测因素。开发了一个简单的基于点的风险评分，以允许患者选择和结果预测。
共收集了 524 例中位年龄为 59 岁、腹膜癌指数中位值为 7（四分位距：3-12）的患者的数据。505 例患者可完全切除；总发病率和 90 天死亡率分别为 50.9%和 2.1%。多因素分析显示，PCI[风险比（HR）：1.08]、N1 期（HR：2.15）、N2 期（HR：2.57）、G3 期（HR：1.80）以及 KRAS（HR：1.46）和 BRAF（HR：3.97）突变显著降低了 CRS/HIPEC 后的生存。RAS/RAF 突变独立于针对 EGFR 的靶向治疗而影响生存。因此，基于 PCI、N、G 和 RAS/RAF 状态，开发了一种简单的基于点的风险评分 BIOSCOPE（结直肠腹膜转移的生物学评分），该评分具有良好的区分度[开发区的曲线下面积（AUC）=0.72，验证 AUC=0.70]、校准（P=0.401），并允许将患者分为 4 组，具有明显不同的生存结果。
RAS/RAF 突变会影响 CRS/HIPEC 后的生存。新的 BIOSCOPE 评分反映了肿瘤生物学，充分分层了长期预后，并改善了患者评估和选择。
