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首页 » 癌症研究 » Lancet Oncol:新方法可估算胃肠间质瘤复发的风险

Lancet Oncol:新方法可估算胃肠间质瘤复发的风险

来源:医脉通 2011-12-12 13:23

近日,国际著名杂志Lancet Oncology在线刊登了芬兰科学家的最新的研究成果“Risk of recurrence of gastrointestinal stromal tumour after surgery: an analysis of pooled population-based cohorts。”研究人员在文章中指出,他们已经开发出一种新方法,可以估算胃肠间质瘤(GIST)患者复发的风险,该项工具可以更准确判断哪些病人复发风险高,哪些病人更易从辅助全身化疗上受益。

对可手术的GIST患者进行复发风险评估越来越重要了。基于ASCO2011上报道的SSGXVIII/AIO试验,辅助伊马替尼辅助治疗的标准周期现在延长至3年,然而3年的伊马替尼辅助治疗不仅与无复发生存期和总生存期改善有关,还与不良反应有关。因此,确定哪些GIST病人需要辅助治疗是一个关键性的挑战。目前,许多GIST病人都给予伊马替尼治疗,即使有些病人只通过手术就可以治愈。

在以前,通常使用的风险分层方案的准确性是未知的,也没有进行充分比较。在这些方案中有丝分裂和肿瘤大小的分割点可能不是最佳的。

新模型降低成本

同期述评中,Anette Duensing博士说道,这篇文章提供了非常重要的数据,使用新建立的预测模型,给予临床医生一个坚实的理论方法和理由去区别高风险易复发的亚群。这项个体化的方法将会降低成本和副作用,将重点关注到那些需要辅助治疗的病人身上。

预测复发风险

为了建立这个新模型,作者汇总了人群为基础的队列,手机了2560名手术的GIST病人,都没有接受过辅助治疗。研究人员使用3种常用的复发预测模型去对肿瘤复发的风险进行分层:国家卫生研究所(NIH)共识标准,修订后的共识标准和武装部病理研究所标准。他们还分析了无复发生存期的预后因素。

中位随访期为4.0年(0-45.8),病人诊断为GISI的中位年龄为63岁(9-96)。大多数病人只通过手术就可治愈。手术后15年无复发生存率是59.9%(95%CI,56.2% - 63.6%),第一个10年随访中很少有复发。

主要不良预后因素是大肿瘤的大小,高的有丝分裂计数,胃部其他部位,存在破裂和男性。肿瘤大小和有丝分裂计数与GIST复发风险存在非线性关联。

与最小的肿瘤尺寸(直径<1.1cm)相比,最大的肿瘤尺寸(直径>15.0cm)的HR为27.98(95%CI,8.79 - 89.06,P <0.0001)。相比最低的肿瘤有丝分裂计数(<2/50高倍镜视野),最大的肿瘤有丝分裂数(> 10/50高倍镜视野)的HR是22.09(95%CI,14.98-32.58,P <0.0001)。

考虑到上述关联性,研究人员建立一个预后的热图,红颜色意味着高风险,蓝色意味着低风险。这些预后热图在肿瘤学上是一个新概念,可以与基因表达热图进行比较。因为热度有点难以阅读,研究者开发出了预后等高线图,每个肿瘤的风险用颜色等高线来描绘。

预后图诊断个体风险最准确

研究人员发现,3个主要的风险分层模型估计GIST的10年复发风险都是相当准确的,然而,与传统的风险分层工具相比,从非线性模型而来的等高线图可提供最准确的预后估计。

非线性模型准确预测了复发的风险,曲线下面积(AUC)为0.88(95%CI,0.86-0.90),相比较而言,NIH共识分类标准的AUC为0.79(95%CI0.76-0.81,P <0.0001),修改后的共识标准为0.78(95%CI0.75-0.80; P <0.0001),武装部病理研究所标准为0.82(95%CI0.80-0.85,P <0.0001)。

新的预后工具更为准确一些,与传统工具相比,新的工具考虑了肿瘤大小和有丝分裂计数的连续性和非线性。非线性模型非常适合于个体病人的建议,尤其是那些处在复发风险边缘的病人。(生物谷Bioon.com)

Risk of recurrence of gastrointestinal stromal tumour after surgery: an analysis of pooled population-based cohorts

Prof Heikki Joensuu MD a , Aki Vehtari DSci b, Jaakko Riihimäki MSc b, Toshirou Nishida MD c, Sonja E Steigen MD d, Peter Brabec MSci e, Prof Lukas Plank MD f, Bengt Nilsson MD g, Claudia Cirilli BSc h, Chiara Braconi MD i, Andrea Bordoni MD j, Magnus K Magnusson MD k, Zdenek Linke MD m, Jozef Sufliarsky MD l, Massimo Federico MD n, Jon G Jonasson MD o, Angelo Paolo Dei Tos MD p, Piotr Rutkowski MD q

Background The risk of recurrence of gastrointestinal stromal tumour (GIST) after surgery needs to be estimated when considering adjuvant systemic therapy. We assessed prognostic factors of patients with operable GIST, to compare widely used risk-stratification schemes and to develop a new method for risk estimation. Methods Population-based cohorts of patients diagnosed with operable GIST, who were not given adjuvant therapy, were identified from the literature. Data from ten series and 2560 patients were pooled. Risk of tumour recurrence was stratified using the National Institute of Health (NIH) consensus criteria, the modified consensus criteria, and the Armed Forces Institute of Pathology (AFIP) criteria. Prognostic factors were examined using proportional hazards and non-linear models. The results were validated in an independent centre-based cohort consisting of 920 patients with GIST. Findings Estimated 15-year recurrence-free survival (RFS) after surgery was 59·9% (95% CI 56·2—63·6); few recurrences occurred after the first 10 years of follow-up. Large tumour size, high mitosis count, non-gastric location, presence of rupture, and male sex were independent adverse prognostic factors. In receiver operating characteristics curve analysis of 10-year RFS, the NIH consensus criteria, modified consensus criteria, and AFIP criteria resulted in an area under the curve (AUC) of 0·79 (95% CI 0·76—0·81), 0·78 (0·75—0·80), and 0·82 (0·80—0·85), respectively. The modified consensus criteria identified a single high-risk group. Since tumour size and mitosis count had a non-linear association with the risk of GIST recurrence, novel prognostic contour maps were generated using non-linear modelling of tumour size and mitosis count, and taking into account tumour site and rupture. The non-linear model accurately predicted the risk of recurrence (AUC 0·88, 0·86—0·90). Interpretation The risk-stratification schemes assessed identify patients who are likely to be cured by surgery alone. Although the modified NIH classification is the best criteria to identify a single high-risk group for consideration of adjuvant therapy, the prognostic contour maps resulting from non-linear modelling are appropriate for estimation of individualised outcomes. Funding Academy of Finland, Cancer Society of Finland, Sigrid Juselius Foundation and Helsinki University Research Funds.

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