近日,，國際著名雜志Lancet Oncology在線刊登了芬蘭科學(xué)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,。”研究人員在文章中指出,，他們已經(jīng)開發(fā)出一種新方法,，可以估算胃腸間質(zhì)瘤（GIST）患者復(fù)發(fā)的風(fēng)險,，該項工具可以更準(zhǔn)確判斷哪些病人復(fù)發(fā)風(fēng)險高，哪些病人更易從輔助全身化療上受益,。
對可手術(shù)的GIST患者進(jìn)行復(fù)發(fā)風(fēng)險評估越來越重要了,。基于ASCO2011上報道的SSGXVIII/AIO試驗,，輔助伊馬替尼輔助治療的標(biāo)準(zhǔn)周期現(xiàn)在延長至3年,，然而3年的伊馬替尼輔助治療不僅與無復(fù)發(fā)生存期和總生存期改善有關(guān)，還與不良反應(yīng)有關(guān),。因此,，確定哪些GIST病人需要輔助治療是一個關(guān)鍵性的挑戰(zhàn)。目前,，許多GIST病人都給予伊馬替尼治療,，即使有些病人只通過手術(shù)就可以治愈。
在以前,，通常使用的風(fēng)險分層方案的準(zhǔn)確性是未知的,，也沒有進(jìn)行充分比較。在這些方案中有絲分裂和腫瘤大小的分割點可能不是最佳的,。
新模型降低成本
同期述評中,，Anette Duensing博士說道，這篇文章提供了非常重要的數(shù)據(jù),，使用新建立的預(yù)測模型,，給予臨床醫(yī)生一個堅實的理論方法和理由去區(qū)別高風(fēng)險易復(fù)發(fā)的亞群。這項個體化的方法將會降低成本和副作用,，將重點關(guān)注到那些需要輔助治療的病人身上,。
預(yù)測復(fù)發(fā)風(fēng)險
為了建立這個新模型，作者匯總了人群為基礎(chǔ)的隊列,，手機(jī)了2560名手術(shù)的GIST病人,，都沒有接受過輔助治療。研究人員使用3種常用的復(fù)發(fā)預(yù)測模型去對腫瘤復(fù)發(fā)的風(fēng)險進(jìn)行分層：國家衛(wèi)生研究所（NIH）共識標(biāo)準(zhǔn),，修訂后的共識標(biāo)準(zhǔn)和武裝部病理研究所標(biāo)準(zhǔn),。他們還分析了無復(fù)發(fā)生存期的預(yù)后因素。
中位隨訪期為4.0年（0-45.8）,，病人診斷為GISI的中位年齡為63歲（9-96）,。大多數(shù)病人只通過手術(shù)就可治愈。手術(shù)后15年無復(fù)發(fā)生存率是59.9%（95%CI,，56.2% - 63.6%）,，第一個10年隨訪中很少有復(fù)發(fā),。
主要不良預(yù)后因素是大腫瘤的大小，高的有絲分裂計數(shù),，胃部其他部位,，存在破裂和男性。腫瘤大小和有絲分裂計數(shù)與GIST復(fù)發(fā)風(fēng)險存在非線性關(guān)聯(lián),。
與最小的腫瘤尺寸（直徑<1.1cm）相比,，最大的腫瘤尺寸（直徑>15.0cm）的HR為27.98（95％CI，8.79 - 89.06,，P <0.0001）,。相比最低的腫瘤有絲分裂計數(shù)（<2/50高倍鏡視野），最大的腫瘤有絲分裂數(shù)（> 10/50高倍鏡視野）的HR是22.09（95％CI,，14.98-32.58,，P <0.0001）。
考慮到上述關(guān)聯(lián)性,，研究人員建立一個預(yù)后的熱圖,，紅顏色意味著高風(fēng)險，藍(lán)色意味著低風(fēng)險,。這些預(yù)后熱圖在腫瘤學(xué)上是一個新概念,，可以與基因表達(dá)熱圖進(jìn)行比較。因為熱度有點難以閱讀,，研究者開發(fā)出了預(yù)后等高線圖,，每個腫瘤的風(fēng)險用顏色等高線來描繪。
預(yù)后圖診斷個體風(fēng)險最準(zhǔn)確
研究人員發(fā)現(xiàn),，3個主要的風(fēng)險分層模型估計GIST的10年復(fù)發(fā)風(fēng)險都是相當(dāng)準(zhǔn)確的,，然而，與傳統(tǒng)的風(fēng)險分層工具相比,，從非線性模型而來的等高線圖可提供最準(zhǔn)確的預(yù)后估計。
非線性模型準(zhǔn)確預(yù)測了復(fù)發(fā)的風(fēng)險,，曲線下面積（AUC）為0.88（95％CI,，0.86-0.90），相比較而言,，NIH共識分類標(biāo)準(zhǔn)的AUC為0.79（95％CI0.76-0.81,，P <0.0001），修改后的共識標(biāo)準(zhǔn)為0.78（95％CI0.75-0.80; P <0.0001）,，武裝部病理研究所標(biāo)準(zhǔn)為0.82（95％CI0.80-0.85,，P <0.0001）。
新的預(yù)后工具更為準(zhǔn)確一些,，與傳統(tǒng)工具相比,，新的工具考慮了腫瘤大小和有絲分裂計數(shù)的連續(xù)性和非線性。非線性模型非常適合于個體病人的建議，尤其是那些處在復(fù)發(fā)風(fēng)險邊緣的病人,。（生物谷Bioon.com）
doi: 10.1016/S1470-2045(11)70299-6
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PMID:
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.
