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Metastatic colorectal cancer prior to expanded RAS assessment: evidence from long-term outcome analysis of a real-life cohort within a dedicated colorectal cancer unit

扩大 RAS 评估前的转移性结直肠癌: 来自专用结直肠癌单元内真实队列的长期结局分析的证据

  • 影响因子:2.06
  • DOI:10.1186/s12957-020-01844-5
  • 作者列表:"Luca Bertero","Rosella Spadi","Simona Osella-Abate","Sara Mariani","Isabella Castellano","Alessandro Gambella","Patrizia Racca","Mario Morino","Paola Cassoni
  • 发表时间:2020-04-03

Abstract Background Molecular assessment and treatment of metastatic colorectal cancer (mCRC) quickly evolved during the last decades, hampering longitudinal evaluation of prognostic markers. The aim of this study was to evaluate prognostic predictors of long-term survival in a retrospective series of mCRC, treated prior to the expanded RAS assessment era. Methods mCRC cases treated at the Città della Salute e della Scienza University Hospital (Turin, Italy) between January 2004 and December 2012 were evaluated, including cases with ≥ 5-year follow-up only. Long-term survival was defined as an overall survival (OS) ≥ 4 years based on the observed OS interquartile range values. Univariate/multivariate Cox proportional hazards regression models were performed to assess the prognostic significance of the clinical/biological features, while binary logistic regression models were used to verify their associations with long-term survival. Results Two hundred and forty-eight mCRC cases were included and analyzed. Sixty out of two hundred and forty-eight (24%) patients were long-term survivors. Univariate binary logistic regression analysis demonstrated a significant association between long-term survival and age at diagnosis < 65 (OR = 2.28, p = 0.007), single metastatic site (OR = 1.89, p = 0.039), surgical resection of metastases (OR = 5.30, p < 0.001), local non-surgical treatment of metastases (OR = 4.74, p < 0.001), and a bevacizumab-including first-line treatment schedule (OR = 2.19, p = 0.024). Multivariate binary logistic regression analysis confirmed the prognostic significance of surgical resection of metastases (OR = 3.96, p < 0.001), local non-surgical treatment of metastases (OR = 3.32, p = 0.001), and of bevacizumab-including first-line treatment schedule (OR = 2.49, p = 0.024). Conclusion Long-term survival could be achieved in a significant rate of patients with mCRC even in an era of limited molecular characterization. Local treatment of metastases proved to be a significant predictor of long-term survival.


摘要背景转移性结直肠癌(mCRC)的分子评估和治疗在过去几十年中迅速发展,阻碍了对预后标志物的纵向评估。这项研究的目的是评估一系列回顾性的mCRC中长期生存的预后预测因子,这些mCRC是在扩大RAS评估时代之前治疗的。方法对2004年1月至2012年12月间在意大利都灵市德拉萨尔德拉西恩扎大学医院接受mCRC治疗的病例进行评估,包括仅随访5年以上的病例。根据观察到的OS四分位数范围值,长期生存率定义为总生存率(OS)≥4 年。采用单变量/多变量Cox比例危险度回归模型评估临床/生物学特征的预后意义,同时采用二元logistic回归模型验证其与长期生存的相关性。结果纳入分析248例mCRC患者。248名患者中有60名(24%)是长期存活者。单因素二元logistic回归分析显示长期生存率与诊断年龄<65岁(OR=2.28,p=0.007)、单发转移灶(OR=1.89,p=0.039)、手术切除转移灶(OR=5.30,p<0.001)、局部非手术治疗转移灶(OR=4.74,p<0.001)有显著相关性,贝伐单抗包括一线治疗计划(OR=2.19,p=0.024)。多因素二元logistic回归分析证实了手术切除转移瘤(OR=3.96,p<0.001)、局部非手术治疗转移瘤(OR=3.32,p=0.001)和贝伐单抗(OR=2.49,p=0.024)的预后意义。结论即使在分子特征有限的时代,mCRC患者的长期生存率也很高。转移瘤的局部治疗被证明是长期生存的重要预测因素。



来源期刊:The FEBS journal
作者列表:["Sayed IM","Suarez K","Lim E","Singh S","Pereira M","Ibeawuchi SR","Katkar G","Dunkel Y","Mittal Y","Chattopadhyay R","Guma M","Boland BS","Dulai PS","Sandborn WJ","Ghosh P","Das S"]

METHODS::Chronic diseases, including inflammatory bowel disease (IBD) urgently need new biomarkers as a significant proportion of patients, do not respond to current medications. Inflammation is a common factor in these diseases and microbial sensing in the intestinal tract is critical to initiate the inflammation. We have identified ELMO1 (Engulfment and Cell Motility Protein-1) as a microbial sensor in epithelial and phagocytic cells that turns on inflammatory signals. Using a stem-cell-based "gut-in-a-dish" coculture model, we studied the interactions between microbes, epithelium and monocytes in the context of IBD. To mimic the in-vivo cell physiology, enteroid-derived monolayers (EDMs) were generated from the organoids isolated from WT and ELMO1-/- mice and colonic biopsies of IBD patients. The EDMs were infected with the IBD-associated microbes to monitor the inflammatory responses. ELMO1-depleted EDMs displayed a significant reduction in bacterial internalization, a decrease in pro-inflammatory cytokine productions and monocyte recruitment. The expression of ELMO1 is elevated in the colonic epithelium and in the inflammatory infiltrates within the lamina propria of IBD patients where the higher expression is positively correlated with the elevated expression of pro-inflammatory cytokines, MCP-1 and TNF-α. MCP-1 is released from the epithelium and recruits monocytes to the site of inflammation. Once recruited, monocytes require ELMO1 to engulf the bacteria and propagate a robust TNF-α storm. These findings highlight that the dysregulated epithelial ELMO1→MCP-1 axis can serve as an early biomarker in the diagnostics of IBD and other inflammatory disorders.

作者列表:["Prathapan KM","Ramos Rivers C","Anderson A","Koutroumpakis F","Koutroubakis IE","Babichenko D","Tan X","Tang G","Schwartz M","Proksell S","Johnston E","Hashash JG","Dunn M","Wilson A","Barrie A","Harrison J","Hartman D","Kim SC","Binion DG"]

METHODS:BACKGROUND:Peripheral blood eosinophilia (PBE) is a biomarker of an aggressive multiyear natural history in adults with inflammatory bowel diseases (IBDs). Additionally, PBE at diagnosis is associated with higher disease activity in pediatric-onset IBD. We sought to determine if PBE can function as a biomarker of long-term disease severity in pediatric-onset IBD patients who are followed into adulthood. METHODS:We analyzed a consented, prospective, natural history IBD registry at an adult tertiary center from 2009 to 2018. Prevalence of PBE was evaluated in both pediatric- and adult-onset IBD patients. Demographics, clinical characteristics, and health care utilization data were compared in patients with and without PBE. RESULTS:Among 2800 adult IBD patients, 23.4% had pediatric-onset disease. PBE was found in 34% of the pediatric-onset patients compared with 26.8% of the adult-onset IBD patients (P < 0.001). In the pediatric-onset IBD cohort, PBE was associated with higher rates of allergies (P < 0.0001), but not of asthma, allergic rhinitis, or primary sclerosing cholangitis. In the adult IBD patients with pediatric-onset disease, PBE was associated with higher rates of C-reactive protein elevation (P < 0.0001), erythrocyte sedimentation rate elevation (P < 0.0001), higher health care utilization, and higher average health care charges per year (P < 0.00001). CONCLUSIONS:Peripheral blood eosinophilia was more prevalent in adult IBD patients with pediatric-onset compared with adult-onset disease. Among all IBD patients with long-term follow-up, PBE defined a subgroup with more severe illness. These data suggest that PBE may be a biomarker for a high-risk subgroup with high cost trajectory and long-term severity in pediatric-onset IBD that persists into adulthood.

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作者列表:["Ronchetti S","Gentili M","Ricci E","Migliorati G","Riccardi C"]

METHODS::Inflammatory bowel diseases (IBDs) are chronic inflammatory disorders with a complex pathogenesis, affecting people of all ages. They are characterized by alternating phases of clinical relapse and remission, depending on the fine balance between immune cells and the gut microbiota. The cross talk between cells of the immune system and the gut microbiota can result in either tolerance or inflammation, according to multifactorial triggers, ranging from environmental factors to genetic susceptibility. Glucocorticoid (GC) administration remains the first-line treatment for IBDs, although long-term use is limited by development of serious adverse effects. Recently, new alternative pharmacological therapies have been developed, although these are not always effective in IBD patients. There is a constant demand for effective new drug targets to guarantee total remission and improve the quality of life for IBD patients. The glucocorticoid-induced leucine zipper (GILZ) has been implicated as a promising candidate for this purpose, in view of its powerful anti-inflammatory effects that mimic those of GCs while avoiding their unwanted adverse reactions. Here we present and discuss the latest findings about the involvement of GILZ in IBDs.

关键词: GILZ IBD 自身免疫 炎症
翻译标题与摘要 下载文献