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新的美国癌症联合委员会胃肠间质瘤分期系统的临床实用性:原发性肿瘤切除后的当前总体生存率。

Clinical utility of the new American Joint Committee on Cancer staging system for gastrointestinal stromal tumors: current overall survival after primary tumor resection.

机构信息

Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland.

出版信息

Cancer. 2011 Nov 1;117(21):4916-24. doi: 10.1002/cncr.26079. Epub 2011 Mar 31.

Abstract

BACKGROUND

The objectives of the current study were to assess the reliability of the new revision of the American Joint Committee on Cancer (AJCC) staging system for gastrointestinal stromal tumors (GISTs) based on the National Comprehensive Cancer Network-Armed Forces Institute of Pathology risk classification and to analyze the factors that influence after resection for primary GISTs in 2 AJCC groups: patients with GISTs originating from the stomach and omentum (G-GISTs) and patients with other primary GISTs located mainly in the small bowel (nongastric GISTs [NG-GISTs]).

METHODS

The authors prospectively analyzed a group of 640 patients with primary, CD117-positive GISTs who underwent surgery with curative intention (R0/R1 resection), including 340 G-GISTs (55.5%) and 300 NG-GISTs (44.5%). Factors were explored that had an effect on disease-free survival time (DFS), which was calculated from the date of radical operation to the date of recurrence or last follow-up. The median follow-up was 39 months.

RESULTS

Compared with NG-GISTs, G-GISTs were characterized by a significantly lower median size (5.3 cm and 8.5 cm, respectively; P < .0001) and lower mitotic activity (median, 3 in 50 high-power fields [HPF] vs 5 in 50 HPF; P < .0001), and they were diagnosed in older patients (median age, 62 years vs 57 years; P = .002). The most commonly detected mutations in G-GIST were those located in KIT exon 11 (60.5%) and platelet-derived growth factor receptor alpha (PDGFRA) exon 18 (19%) versus KIT exons 11 and 9 in NG-GISTs (72% and 17.4%, respectively). The prognosis of patients who had G-GISTs was significantly better compared that of patients who had NG-GISTs, with 5-year DFS rates of 69% (median, 83 months) versus 43% (median, 33 months), respectively (P < .00001). The most significant prognostic factors that correlated with shorter DFS in both G-GISTs and NG-GISTs were primary tumor size >5 cm and >10 cm (P < .0001) and mitotic index >5 in 50 HPF and >10 in 50 HPF (P < .0001). The 5-year DFS rates in G-GISTs according to AJCC stage categories were as follows: 96% for stage IA tumors, 92% for stage IB tumors, 51% for II tumors, 22% for stage IIIA tumors, and 22% for stage IIIB tumors (P < .0001). The 5-year DFS rates in NG-GISTs according to AJCC categories were as follows: 92% for stage I tumors, 66% for stage II tumors, 28% for IIIA tumors, and 16% for IIIB tumors (P < .0001). The high prognostic significance of the AJCC classification also was confirmed for overall survival data, including the impact of therapy with tyrosine kinase inhibitors.

CONCLUSIONS

The reliability of AJCC risk classification after resection of primary GIST was confirmed for DFS and overall survival. Patients with primary G-GISTs had a better prognosis than patients with NG-GISTs. In both groups, primary tumor size and mitotic activity were the most important prognostic factors in terms of DFS.

摘要

背景

本研究的目的是评估基于国家综合癌症网络-武装部队病理风险分类的胃肠道间质瘤(GIST)新版美国癌症联合委员会(AJCC)分期系统的可靠性,并分析 2 个 AJCC 组中主要接受原发性 GIST 切除术后的影响因素:胃和网膜来源的 GIST(G-GISTs)患者和主要位于小肠的其他原发性 GIST 患者(非胃 GIST [NG-GISTs])。

方法

作者前瞻性分析了 640 例接受根治性手术(R0/R1 切除)的原发性、CD117 阳性 GIST 患者,包括 340 例 G-GISTs(55.5%)和 300 例 NG-GISTs(44.5%)。探索了影响无病生存时间(DFS)的因素,DFS 从根治性手术日期计算至复发或最后一次随访日期。中位随访时间为 39 个月。

结果

与 NG-GISTs 相比,G-GISTs 的特征是肿瘤中位大小明显较小(分别为 5.3 cm 和 8.5 cm;P <.0001)和有丝分裂活性较低(中位值,50 高倍视野[HPF]中有 3 个 vs 50 HPF 中有 5 个;P <.0001),且诊断时患者年龄较大(中位年龄,62 岁 vs 57 岁;P =.002)。G-GISTs 最常见的突变是 KIT 外显子 11(60.5%)和血小板衍生生长因子受体 alpha(PDGFRA)外显子 18(19%),而 NG-GISTs 中最常见的突变是 KIT 外显子 11 和 9(分别为 72%和 17.4%)。G-GISTs 患者的预后明显优于 NG-GISTs 患者,5 年 DFS 率分别为 69%(中位值,83 个月)和 43%(中位值,33 个月)(P <.00001)。在 G-GISTs 和 NG-GISTs 中与较短 DFS 相关的最显著预后因素是原发肿瘤大小>5 cm 和>10 cm(P <.0001)和 50 HPF 中有丝分裂指数>5 和>10(P <.0001)。G-GISTs 根据 AJCC 分期的 5 年 DFS 率如下:IA 期肿瘤为 96%,IB 期肿瘤为 92%,II 期肿瘤为 51%,IIIA 期肿瘤为 22%,IIIB 期肿瘤为 22%(P <.0001)。NG-GISTs 根据 AJCC 分期的 5 年 DFS 率如下:I 期肿瘤为 92%,II 期肿瘤为 66%,IIIA 期肿瘤为 28%,IIIB 期肿瘤为 16%(P <.0001)。AJCC 分类对总生存数据的高预后意义也得到了证实,包括酪氨酸激酶抑制剂治疗的影响。

结论

原发性 GIST 切除术后 AJCC 风险分类的可靠性得到了 DFS 和总生存数据的证实。G-GISTs 患者的预后优于 NG-GISTs 患者。在这两个组中,原发肿瘤大小和有丝分裂活性是 DFS 最重要的预后因素。

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