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【2017ASCO GI】“左”“右”之争新数据：聚焦早期结直肠癌预后

2017年01月29日

整理：Max

来源：医脉通肿瘤科

Ⅲ期研究CALGB/SWOG 80405的回顾性分析揭示了转移性结直肠癌中肿瘤解剖部位与预后的相关性。起源于左侧结肠（结肠脾曲、降结肠、乙状结肠和直肠）的患者与右侧（盲肠、升结肠）相比预后更好。

2017年1月ASCO胃肠肿瘤研讨会（GI）在美国旧金山召开。当地时间21日的口头报告上，来自以色列大卫杜夫癌症中心的Irit Ben-Aharon博士以“Sidedness matters: Surrogate biomarkers prognosticate colorectal cancer upon anatomic location”为题，报道了结直肠癌原发灶部位和Oncotype DX、CDX2的关系，以及对早期患者预后的影响。

Oncotype DX是一种临床验证过的结肠癌12基因检测，可用于Ⅱ期结直肠癌患者复发风险预测。另外，先前的研究提示CDX2阴性结直肠癌常与一些预后不良因素（ALCAM高表达、病理级别高、侵袭性强）相关。而在无辅助化疗的情况下，与CDX2阳性患者相比，CDX2阴性患者的无病生存率下降。

研究内容

该研究纳入2011年1月至2016年2月经Oncotype DX 12基因检测，错配修复基因完善（MMR-P）的Ⅱ期（T3）结直肠癌共1087例。回顾患者的病理报告，提取原发肿瘤位置和CDX2免疫染色信息。

分析复发评分（RS）和CDX2表达与结直肠原发部位的关系。

主要结果

基本统计：患者中位年龄69岁，肿瘤部位在右侧占46%（n=500，包括盲肠、升结肠和横结肠），左侧占54%（n=587，包括结肠脾区、降结肠、乙状结肠和直肠）

与左侧结直肠癌相比，右侧肿瘤的复发评分明显更高（27.72 vs 25.79），并自右向左逐渐降低：直肠（29.75）→肝曲（27.76）→乙状结肠（24.49）。

与左侧结直肠癌相比，右侧肿瘤中CDX2阴性表达占比较高（35.8% vs 16.1%）。

不出意外，对于Oncotype DX检测而言，CDX2阴性肿瘤与阳性肿瘤相比，前者的复发评分更高（32.00 vs 24.42）。

从一个包含132例Ⅲ期结直肠癌的小样本队列可知，右侧肿瘤的复发评分依旧高于左侧（31.15 vs 24.60）。此外，Ⅱ/Ⅲ期左侧直肠癌的复发评分明显高于左侧结肠癌（Ⅱ:27.06 vs. 24.60；Ⅲ:27.15 vs 25.79）。

研究结论

这项研究提示，Ⅱ期MMR-P的结直肠癌中，右半肿瘤的预后可能要比左半肿瘤更差。肿瘤原发位置应该纳入到结直肠癌复发风险和辅助治疗的评估之中。

虽然研究证实了Oncotype DX复发评分和CDX2状态与原发肿瘤部位存在相关性，但肿瘤部位不足以成为早期患者的预后因子，在指导临床前还需要进一步分析。

Sidedness matters: Surrogate biomarkers prognosticate colorectal cancer upon anatomic location.

J Clin Oncol 35, 2017 (suppl 4S; abstract 523)

Author(s):

Irit Ben-Aharon,

Abstract:

Background:

Recent evidence indicate that the anatomic location of primary tumors across the colon correlate with survival in the metastatic setting, whereas left-sided tumors may exhibit superior survival compared with right-sided. The Oncotype DX, a 12-gene colon cancer assay, is a clinically validated predictor of recurrence risk in stage II colorectal cancer (CRC) patients. Previous studies had indicated that CDX2-negative colorectal tumors are often associated with several adverse prognostic variables. Recently, it has been shown that without adjuvant chemotherapy, CDX2-negative stage II CRC tumors were associated with a lower rate of disease-free survival than CDX2-positive stage II CRC tumors. We aimed to evaluate whether these validated two prognostic biomarkers may correlate with primary tumor location, and whether tumor location may reflect differential prognosis in stage II CRC.

Methods:

We retrospectively analyzed a cohort of patients with T3 mismatch repair proficient (MMR-P) stage II CRC for whom 12-gene assay was performed (between 1/2011-2/2016). Pathological report was reviewed for exact primary tumor location and CDX2 immunostaining. Recurrence score (RS) and CDX2 expression were correlated with primary tumor location.

Results:

The analysis included 1087 patients with MMR-P stage II CRC (median age 69 years (range 29-93)). Tumor distribution across the colon was as follows: 46% (n = 500) were right-sided (cecum, ascending colon, transverse colon) and 54% (n = 587) were left-sided (splenic flexure, descending colon, sigmoid colon and rectum). Recurrence score was higher in right-sided tumors compared with left-sided tumors (p = 0.01). The RS gradually decreased across the colon (cecum - highest score, sigmoid-lowest score, p = 0.04). Right-sided tumors exhibited more CDX2-negative tumors compared with left-sided tumors (p = 0.07).

Conclusions:

Our study indicate that right-sided colorectal tumors may display worse prognosis compared with left-sided tumors in MMR-P stage II CRC. Primary tumor location may serve as a prognostic factor that should be accounted for recurrence risk assessment and consideration of adjuvant treatment.

参考文献：

1. Irit Ben-Ahar on.et al. J Clin Oncol 35, 2017 (suppl 4S; abstract 523)

2. Kara Nyberg. New Studies Offer Insight Into Implications of Left- Versus Right-Sided Primary Tumor Location in CRC. Gicasym.org.

编辑：肿瘤资讯-小编