Analysis of metastasis and survival after different treatment in patients with T1 stage colonic neuroendocrine tumors
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摘要:目的
探讨T1期结肠神经内分泌肿瘤（colonic neuroendocrine tumor, C-NET）转移率及相关危险因素，比较未转移（T1N0M0期）C-NET患者接受局部切除治疗（local excision, LE）或根治性手术治疗（radical surgery, RS）后的长期生存情况。
方法分析SEER数据库内2004年1月1日至2015年12月31日经病理学诊断为T1期C-NET患者的相关信息。采用Cox回归分析评估C-NET患者发生转移的影响因素。将未发生转移的C-NET患者分为LE组和RS组，并采用倾向得分匹配（propensity score matching, PSM），根据患者性别、年龄、肿瘤最大径、浸润深度进行1∶1匹配，卡钳值设定为0.02。使用Kaplan-Meier生存曲线来分析患者5年癌症特异性生存（cancer-specific survival, CSS）和总生存（overall survival, OS）。采用Cox回归分析评估转移对生存的影响。
结果共纳入419例T1期C-NET患者，其中19例（4.53%）发生远处转移。多因素Cox回归分析显示，肿瘤最大径为11~20 mm（HR=9.264，95% CI 3.322~25.835，P＜0.001）、肿瘤位于右结肠（HR=0.116，95% CI 0.042~0.321，P＜0.001）和黏膜下浸润（HR=5.842，95% CI 1.858~18.371，P=0.003）是T1期C-NET远处转移的独立危险因素。未转移与转移患者的5年OS率分别是94.5%和47.4%（χ2=79.762, P＜0.001），5年CSS率分别为99.5%和55.7%（χ2=164.604，P＜0.001）。PSM前未转移C-NET患者LE及RS后5年OS率为95.8%、90.1%（χ2=2.679，P=0.063），5年CSS率为100.0%和97.2%（χ2=0.579，P=0.038）；PSM后患者LE及RS后5年OS率为96.8%和92.1%（χ2=3.606，P=0.058），5年CSS率为100.0%和98.5%（χ2=1.015，P=0.314）。PSM后LE组和RS组按肿瘤位置、肿瘤最大径和黏膜下浸润分层患者间5年OS和CSS差异均无统计学意义。
结论肿瘤最大径11~20 mm、位于右结肠和黏膜下浸润是T1期C-NET远处转移的独立危险因素；LE可作为未转移T1期C-NET的合适治疗方案。
Abstract:ObjectiveTo explore the metastasis rate and related risk factors of T1 stage colonic neuroendocrine tumor (C-NET), and to compare the long-term survival outcomes of patients with non-metastatic (T1N0M0 stage) C-NET after local excision (LE) or radical surgery (RS).
MethodsClinical information of 433 patients diagnosed with C-NET in the SEER database from January 1, 2004 to December 31, 2015 were analyzed. Cox regression was used to analyze the influencing factors of metastasis of C-NET. The patients without metastasis were divided into LE group and RS group, and assigned in a 1∶1 ratio using propensity score matching (PSM) according to gender, age, tumor largest diameter, and infiltration depth, with a caliper value set to 0.02. Kaplan-Meier survival curve was used to analyze 5-year cancer-specific survival (CSS) and overall survival (OS) of patients. Cox regression analysis was used to evaluate the influence of metastasis on survival.
ResultsAmong 419 C-NET patients, 19(4.52%) had distant metastases. Cox regression analysis showed that 11-20 mm of tumor large diameter (HR=9.264, 95%CI 3.322-25.835, P < 0.001), right colon location (HR=0.116, 95%CI 0.042-0.321, P < 0.001), and submucosal invasion (HR=5.842, 95%CI 1.858-18.371, P=0.003) were independent risk factors for distant metastasis of T1 stage C-NET. The 5-year OS rates of non-metastatic and metastatic patients were 94.5% and 47.4%, respectively (χ2=79.762, P < 0.001), and their 5-year CSS rates were 99.5% and 55.7%, respectively (χ2=164.604, P < 0.001). Before PSM, the 5-year OS rates of non-metastatic C-NET patients after LE and RS were 95.8% and 90.1% (χ2=2.679, P=0.063), and the 5-year CSS rates were 100.0% and 97.2% (χ2=0.579, P=0.038); after PSM, the 5-year OS rates of non-metastatic patients after LE and RS were 96.8% and 92.1% (χ2=3.606, P=0.058), and the 5-year CSS rates were 100.0% and 98.5% (χ2=1.015, P=0.314). After PSM, there was no significant difference in the 5-year OS and CSS of patients with defferent tumor location, tumor large diameter, or submucosal invasion between the LE and RS groups.
Conclusions11-20 mm of tumor diameter, right colon location, and submucosal invasion might be independent risk factors for distant metastasis of T1 stage C-NET, and LE could be an appropriate treatment option for non-metastatic C-NET.
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Keywords:
- neuroendocrine tumor /
- colon /
- treatment strategie /
- metastasis /
- SEER database
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神经内分泌肿瘤（neuroendocrine tumor, NET）是来源于神经内分泌细胞的罕见肿瘤，其中约2/3发生在胃肠道[1-2]。结肠NET（colonic NET, C-NET）的发病率低于直肠、小肠和阑尾NET，但是结肠中第二常见的恶性肿瘤[1, 3-4]。
近年来，结直肠NET的发病率呈上升趋势[5]。C-NET较直肠NET更具侵袭性，且分化程度较低，诊断时转移率高[2, 6]。切除是结直肠NET的首选治疗方案[7]。随着结肠镜的广泛使用，局部切除（local excision, LE）在小结直肠NET中的应用越来越多。然而，由于C-NET的独特临床特征，目前其治疗方案在全球指南间存在差异。美国国立综合癌症网络（The US National Comprehensive Cancer Network, NCCN）指南[8]推荐对C-NET进行肠段切除和局部淋巴结清扫；日本神经内分泌肿瘤学会(Japanese Neuroendocrine Tumor Society, JNET)建议对无淋巴血管和肌层侵犯的局部结直肠NET（＜1 cm）进行内镜切除[9]；中国指南[10]则建议对肿瘤最大径≤2 cm、良好分化（G1）/中度分化（G2）C-NET试行内镜下治疗。
本研究对SEER数据库中相关数据进行分析，评估T1期C-NET的转移相关危险因素，并比较进行LE和RS后未转移T1期C-NET患者的长期生存情况，进而评估LE对小型C-NET（最大径小于1 cm）患者的有效性和安全性。
1. 资料与方法
1.1 一般资料
签署SEER研究数据相关协议，访问SEER Research Data 18 Registries（http://www.seer.cancer.gov）中的数据，获取2004年1月1日至2015年12月31日经病理诊断符合《国际疾病分类-肿瘤学第3版》T1期C-NET的患者，患者随访截止日期为2017年12月31日。排除标准：（1）年龄小于18岁或大于80岁；（2）肿瘤低度分化（G3）/未分化或为间变性（G4）；（3）随访时间短于6个月；（4）缺乏淋巴结转移（lymph node metastasis, LNM）或远处转移信息；（5）缺乏手术信息；（6）缺乏肿瘤大小和浸润深度信息；（7）肿瘤最大径＞2 cm。
1.2 观察指标
获取患者的一般信息（诊断年份、年龄、性别），肿瘤特征（部位、侵入深度、肿瘤大小和转移），治疗方式以及随访期间的生存信息。右半结肠包括盲肠、升结肠、结肠肝曲和横结肠；左半结肠包括结肠脾曲、降结肠、乙状结肠和直乙交界处结肠[11]。检索美国外科医师学会癌症委员会的肿瘤登记数据系统中手术代码，将未发生转移（T1N0M0）的患者分为LE（代码：20~29）组和根治手术（RS，代码：30、32、40、41、50、70）组。分析转移风险因素；比较LE组和RS组患者术后5年癌症特异性生存（cancer-specific survival, CSS）和总生存（overall survival, OS）。
1.3 统计学处理
采用SPSS 25.0软件和R 4.3.2软件进行分析，计量资料以x±s表示，组间比较采用t检验；计数资料以n(%)表示，组间比较采用χ2检验或Fisher确切概率法。采用倾向得分匹配（propensity score matching, PSM），根据患者性别、年龄、肿瘤最大径、浸润深度对LE组和RS组患者进行1∶1匹配，卡钳值设定为0.02。通过Kaplan-Meier生存曲线及log-rank检验分析两组患者及不同分层患者间生存差异，采用Cox回归分析评估转移对生存的影响。所有假设均为双侧检验，检验水准（α）为0.05。
2. 结果
2.1 队列特征
共纳入419例T1期C-NET患者，男性202例（48.21%），年龄（54.54±10.956）岁，其中19例（4.52%）发生远处转移。结果（表 1）显示：转移组和未转移组年龄、肿瘤位置、肿瘤最大径和黏膜下层浸润比例差异均有统计学意义（P＜0.001）。
表 1 转移和非转移T1期C-NET患者的临床病理特征比较Table 1. Comparison of clinicopathological features between metastatic and non-metastatic T1 stage C-NET patientIndex No metastasis (n=400) Metastasis (n=19) t/χ2 value P value Age/year 54.12±10.733 63.47±12.089 -3.690 ＜0.001 Gender n(%) 0.096 0.756 Female 206(51.50) 11(57.89) Male 194(48.50) 8(42.11) Site n(%) 33.011 ＜0.001 Right colon 50(12.50) 12(63.16) Left colon 350(87.50) 7(36.84) Grade n(%) 0.016 0.992 G1 153(38.25) 7(36.84) G2 20(5.00) 1(5.26) Unknown 227(56.75) 11(57.89) Tumor size n(%) 25.178 ＜0.001 ≤10 mm 373(93.25) 11(57.89) 11~20 mm 27(6.75) 8(42.11) SMI n(%) 126(31.50) 15(78.95) 16.226 ＜0.001 SMI: submucosal involvement. 2.2 转移患者生存及和转移危险因素
Kaplan-Meier生存分析（图 1）显示：非转移与转移T1期C-NET患者的5年OS率分别为94.5%和47.4%（χ2=79.762，P＜0.000 1），5年CSS率分别为99.5%和55.7%（χ2=164.604，P＜0.000 1）。Cox多因素回归分析（表 2）显示，肿瘤最大径为11~20 mm、位于右结肠和黏膜下浸润是T1期C-NET远处转移的独立危险因素（P＜0.01）。
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图 1 Kaplan-Meier生存曲线分析非转移与转移T1期C-NET患者生存Figure 1. Survival of patients with metastatic and non-metastatic T1 stage C-NET表 2 Cox多因素回归分析T1期C-NET远处转移的危险因素Table 2. Cox multiple regression analysis of risk factors for distant metastasis of T1 stage C-NETParameter HR (95%CI) Regression Coefficient Wald value P value Age (＞60 years vs ≤60 years） 0.881(0.326-2.383) -0.127 0.062 0.803 Sex (male vs female) 0.489(0.181-1.322) -0.715 1.988 0.159 Site (left colon vs right colon) 0.116(0.042-0.321) -2.153 17.195 ＜0.001 Grade (vs G1) G2 1.480(0.172-12.742) 0.392 0.127 0.721 Unknown 0.640(0.227-1.802) -0.447 0.715 0.398 Tumor size (11-20 mm vs ≤10 mm) 9.264(3.322-25.835) 2.226 18.098 ＜0.001 SMI (Yes vs No) 5.842(1.858-18.371) 1.765 9.119 0.003 SMI: submucosal involvement. 2.3 未转移C-NET患者LE组与RS组临床病理特征比较
400例未转移C-NET患者中，325例（81.25%）接受LE治疗，75例（18.75%）接受RS治疗。结果（表 3）显示：LE组和RS组患者肿瘤位置和黏膜下层浸润比例差异有统计学意义（P＜0.001）；匹配后，两组各66例，临床病理指标差异均无统计学意义。
表 3 未转移C-NET患者倾向性匹配前后LE组及RS组临床病理特征比较Table 3. Comparison of clinical and pathological characteristics between LE and RS groups before and after PSM in patients with non-metastatic C-NETIndex Before PSM After PSM LE(n=325) RS(n=75) t/χ2 value P value LE(n=66) RS(n=66) t/χ2 value P value Age/year 54.02±10.231 54.56±12.750 0.393 0.694 56.09±9.959 54.91±12.166 0.611 0.543 Gender n(%) 0.748 0.442 0.030 0.861 Female 161(49.54) 33(44.00) 30(45.45) 31(46.96) Male 164(50.46) 42(56.00) 36(54.55) 35(53.04) Site n(%) 52.046 ＜0.001 0.038 0.846 Right colon 22(6.77) 28(37.33) 18(27.27) 19(28.79) Left colon 303(93.23) 47(62.67) 48(72.73) 47(71.21) Grade n(%) 0.542 0.763 0.162 0.922 G1 125(81.70) 28(37.33) 27(40.91) 26(39.39) G2 15(75.00) 5(6.67) 3(4.54) 4(6.06) Unknown 185(81.50) 42(56.00) 36(54.55) 36(54.55) SMI n(%) 88(61.54) 38(50.67) 15.716 ＜0.001 35(53.04) 34(51.52) 0.030 0.862 Tumor size n(%) 2.250 0.133 0.284 0.791 ≤10 mm 306(94.15) 67(89.33) 57(86.36) 59(89.39) 11-20 mm 19(5.85) 8(10.67) 9(13.64) 7(10.61) PSM: propensity score matching; SMI: submucosal involvement. 2.4 未转移C-NET患者LE、RS术后总体生存分析
Kaplan-Meier生存曲线分析（图 2）显示：PSM前未转移患者LE组和RS组5年OS率为95.8%和90.1%（χ2=2.679，P=0.063），5年CSS率为100.0%和97.2%（χ2=0.579，P=0.038）；PSM后未转移患者LE组和RS组5年OS率为96.8%和92.1%（χ2=3.606，P=0.058），5年CSS率为100.0%和98.5%（χ2=1.015，P=0.314）。
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图 2 Kaplan-Meier生存曲线分析未转移C-NET患者LE组和RS组生存A, B: before propensity score matching; C, D: after propensity score matching.Figure 2. Kaplan-Meier curve for cancer-specific survival (CSS) and overall survival (OS) for T1N0M0 colonic neuroendocrine tumors (NET) patients2.5 未转移C-NET患者LE组、RS组PSM后亚组术后生存分析
结果（图 3、表 4）显示：未转移C-NET患者LE组、RS组PSM后，两组不同肿瘤位置、最大径、浸润黏膜下层与否分层患者间5年OS、CSS差异均无统计学意义。
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图 3 Kaplan-Meier生存曲线未转移C-NET患者PSM后亚组生存A, B: the subgroup with right colon cancer; C, D: the subgroup with left colon cancer; E, F: the subgroup with larger diameter≤10 mm of tumor; G, H: the subgroup without submucosal involvement; I, J: the subgroup with submucosal involvement. 5-year OS rate and 5-year CSS rate were all 100% in LE and RS groups in subgroup with larger diameter 11-20 mm of tumor, so the survival curve was not drawn.Figure 3. Kaplan-Meier curve for survival of patients with T1N0M0 colonic neuroendocrine tumors after PSM matching表 4 未转移C-NET患者PSM后亚组生存分析Table 4. Subgroup analysis of survival of T1N0M0 C-NET patients after PSMIndex LE RS χ2 value P value Site Right colon n=18 n=19 OS(95%CI)/month 173.3(150.7-196.0) 150.4(123.3-177.5) 5-year OS rate/% 93.8 88.4 0.307 0.508 5-year CSS rate/% 100 100 0 1.000 Left colon n=48 n=47 OS(95%CI)/month 185.9(180.0-191.9) 166.3(151.7-180.8) 5-year OS rate/% 97.9 93.5 1.088 0.073 5-year CSS rate/% 100 97.8 1.032 0.310 Tumor size ≤10 mm n=57 n=59 OS(95%CI)/month 182.9(174.1-191.8) 159.7(145.3-174.1) 5-year OS rate/% 96.4 91.1 1.261 0.065 5-year CSS rate/% 100 98.3 0.975 0.324 11-20 mm* n=9 n=7 5-year OS rate/% 100 100 0 1.000 5-year CSS rate/% 100 100 0 1.000 SMI No n=31 n=32 OS(95%CI)/month 180.0(167.8-192.1) 159.2(140.3-178.1) 5-year OS rate/% 96.7 89.8 1.001 0.190 5-year CSS rate/% 100 100 0 1.000 Yes n=35 n=34 OS(95%CI)/month 186.8(178.6-194.9) 165.0(147.5-182.5) 5-year OS rate/% 97.0 93.9 0.380 0.190 5-year CSS rate/% 100 100 1.045 0.030 *5-year OS rate and 5-year CSS rate were all 100%, so the survival curve was not drawn. OS: overall survival; CSS: cancer-specific survival; SMI: submucosal involvement. 3. 讨论
随着内镜技术的普及，胃肠道NET的发现率逐年增加。SEER数据库显示，与1997年相比，2011年胃肠道NET发病率增加了6倍，估计每10万人中有3.56例胃肠道NET[12]。在日本，其发病率从2005年的每10万人中2.07例增加至2010年的每10万人中4.52例[13]。以往C-NET的首选治疗为手术结合局部淋巴结清扫[8]。随着结肠镜筛查的普及和内镜下治疗技术的快速发展，小C-NET的检出率逐年升高，局部切除成为也可能[14]。荷兰一项研究[5]发现，C-NET的内镜切除率从2006年的7%增加至2016年的52%。然而，与临床常见的直肠NET不同，少有研究关注C-NET患者早期远处转移和局部切除后的预后情况。
肿瘤大小是预测结直肠NET转移的关键因素之一[15]。Lee等[16]研究发现，肿瘤大小与肿瘤侵入深度、淋巴侵犯与否和有丝分裂有关。本研究中，最大径11~20 mm肿瘤的转移风险高于最大径≤10 mm肿瘤，浸润黏膜下层者转移率也更高（P＜0.01）。一项纳入929例C-NET患者的研究[17]发现，肿瘤位于黏膜内，最大径＜1 cm者淋巴结转移率为4%。欧洲NET协会推荐，对于最大径＜1 cm、限于黏膜内的患者，进行局部或内窥镜切除而不行淋巴结清扫[18]。
本研究发现，C-NET位于右半结肠者转移率高于位于左半结肠者（P＜0.001），可能与胚胎学起源相关。右半结肠起源于中肠，类似于回肠起源，而左结肠起源于后肠，类似于直肠；同时，不同于多发的回肠NET，右结肠NET多为单发、直径较大，且侵袭性更高；大多数回肠NET细胞为产5-羟色胺的肠嗜铬细胞（enterochromaffin cell, EC），而右结肠NET有较大异质性，包括EC细胞、L细胞和其他类型[18]。因此，对于右半结肠NET，选择治疗方案选择时可能需要更严格的临床评估和辅助检查（内窥镜超声、计算机断层扫描等）；而对于左结肠NET，LE可能安全且有效[19]。肿瘤的偏侧性可能影响各种肿瘤患者的预后，除胚胎学起源外，解剖结构、血液循环和淋巴循环的异质性，以及与周围脏器的关系等可能也是相关因素[20-21]。
本研究发现，T1期C-NET非转移患者5年OS、CSS率均高于转移患者（P＜0.001），证实远处转移是导致C-NET预后不良的重要因素。因此，治疗前通过超声内镜或CT检查远处转移情况具有重要临床意义。未转移直肠NET患者接受LS后可获得长期生存，而未转移C-NET患者的治疗方案目前仍存在争议[22]。尽管NCCN指南推荐将肠切除+淋巴结清扫作为治疗C-NET的首选，但本研究发现LE已成为未转移C-NET的首选方法（325/400，81.25%），且接受LE的患者术后5年OS和CSS与接受RS者相当，提示LE对于该类患者有效且安全。亚组分析中，由于肿瘤最大径为11~20 mm的患者较少，分别仅9例患者行LE治疗、7例患者行RS治疗，这可能是导致两组5年OS和CSS差异无统计学意义的原因。
本研究局限性：（1）由于C-NET的发病率较低，一些亚组患者数量较少。（2）获取了初次治疗数据，但未对患者化疗、放疗及靶向治疗等信息进行分析，可能导致生存结果偏倚。由于针对治疗方式的研究中患者均未出现远处转移，后续治疗影响可能相对较小。（3）SEER数据库中缺乏Ki-67和有丝分裂指数等重要的C-NET分类指标。
综上所述，本研究发现，T1期C-NET患者转移率较低，肿瘤最大径11~20 mm、位于右半结肠和黏膜下浸润是T1期C-NET转移的独立危险因素；在未转移患者中，LS和RS术后5年生存差异不明显，提示对于该类C-NET患者，LE可能是有效且安全的治疗选择。
伦理声明 无。利益冲突 所有作者声明不存在利益冲突。作者贡献 白斌：论文撰写、修改；李恒：数据整理；汪军：图表制作；肖华：数据获取、管理及分析；蔡慧：研究设计。 -
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图 1 Kaplan-Meier生存曲线分析非转移与转移T1期C-NET患者生存
Figure 1. Survival of patients with metastatic and non-metastatic T1 stage C-NET
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图 2 Kaplan-Meier生存曲线分析未转移C-NET患者LE组和RS组生存
A, B: before propensity score matching; C, D: after propensity score matching.
Figure 2. Kaplan-Meier curve for cancer-specific survival (CSS) and overall survival (OS) for T1N0M0 colonic neuroendocrine tumors (NET) patients
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图 3 Kaplan-Meier生存曲线未转移C-NET患者PSM后亚组生存
A, B: the subgroup with right colon cancer; C, D: the subgroup with left colon cancer; E, F: the subgroup with larger diameter≤10 mm of tumor; G, H: the subgroup without submucosal involvement; I, J: the subgroup with submucosal involvement. 5-year OS rate and 5-year CSS rate were all 100% in LE and RS groups in subgroup with larger diameter 11-20 mm of tumor, so the survival curve was not drawn.
Figure 3. Kaplan-Meier curve for survival of patients with T1N0M0 colonic neuroendocrine tumors after PSM matching
表 1 转移和非转移T1期C-NET患者的临床病理特征比较
Table 1 Comparison of clinicopathological features between metastatic and non-metastatic T1 stage C-NET patient
Index No metastasis (n=400) Metastasis (n=19) t/χ2 value P value Age/year 54.12±10.733 63.47±12.089 -3.690 ＜0.001 Gender n(%) 0.096 0.756 Female 206(51.50) 11(57.89) Male 194(48.50) 8(42.11) Site n(%) 33.011 ＜0.001 Right colon 50(12.50) 12(63.16) Left colon 350(87.50) 7(36.84) Grade n(%) 0.016 0.992 G1 153(38.25) 7(36.84) G2 20(5.00) 1(5.26) Unknown 227(56.75) 11(57.89) Tumor size n(%) 25.178 ＜0.001 ≤10 mm 373(93.25) 11(57.89) 11~20 mm 27(6.75) 8(42.11) SMI n(%) 126(31.50) 15(78.95) 16.226 ＜0.001 SMI: submucosal involvement. 
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表 2 Cox多因素回归分析T1期C-NET远处转移的危险因素
Table 2 Cox multiple regression analysis of risk factors for distant metastasis of T1 stage C-NET
Parameter HR (95%CI) Regression Coefficient Wald value P value Age (＞60 years vs ≤60 years） 0.881(0.326-2.383) -0.127 0.062 0.803 Sex (male vs female) 0.489(0.181-1.322) -0.715 1.988 0.159 Site (left colon vs right colon) 0.116(0.042-0.321) -2.153 17.195 ＜0.001 Grade (vs G1) G2 1.480(0.172-12.742) 0.392 0.127 0.721 Unknown 0.640(0.227-1.802) -0.447 0.715 0.398 Tumor size (11-20 mm vs ≤10 mm) 9.264(3.322-25.835) 2.226 18.098 ＜0.001 SMI (Yes vs No) 5.842(1.858-18.371) 1.765 9.119 0.003 SMI: submucosal involvement.
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表 3 未转移C-NET患者倾向性匹配前后LE组及RS组临床病理特征比较
Table 3 Comparison of clinical and pathological characteristics between LE and RS groups before and after PSM in patients with non-metastatic C-NET
Index Before PSM After PSM LE(n=325) RS(n=75) t/χ2 value P value LE(n=66) RS(n=66) t/χ2 value P value Age/year 54.02±10.231 54.56±12.750 0.393 0.694 56.09±9.959 54.91±12.166 0.611 0.543 Gender n(%) 0.748 0.442 0.030 0.861 Female 161(49.54) 33(44.00) 30(45.45) 31(46.96) Male 164(50.46) 42(56.00) 36(54.55) 35(53.04) Site n(%) 52.046 ＜0.001 0.038 0.846 Right colon 22(6.77) 28(37.33) 18(27.27) 19(28.79) Left colon 303(93.23) 47(62.67) 48(72.73) 47(71.21) Grade n(%) 0.542 0.763 0.162 0.922 G1 125(81.70) 28(37.33) 27(40.91) 26(39.39) G2 15(75.00) 5(6.67) 3(4.54) 4(6.06) Unknown 185(81.50) 42(56.00) 36(54.55) 36(54.55) SMI n(%) 88(61.54) 38(50.67) 15.716 ＜0.001 35(53.04) 34(51.52) 0.030 0.862 Tumor size n(%) 2.250 0.133 0.284 0.791 ≤10 mm 306(94.15) 67(89.33) 57(86.36) 59(89.39) 11-20 mm 19(5.85) 8(10.67) 9(13.64) 7(10.61) PSM: propensity score matching; SMI: submucosal involvement.
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表 4 未转移C-NET患者PSM后亚组生存分析
Table 4 Subgroup analysis of survival of T1N0M0 C-NET patients after PSM
Index LE RS χ2 value P value Site Right colon n=18 n=19 OS(95%CI)/month 173.3(150.7-196.0) 150.4(123.3-177.5) 5-year OS rate/% 93.8 88.4 0.307 0.508 5-year CSS rate/% 100 100 0 1.000 Left colon n=48 n=47 OS(95%CI)/month 185.9(180.0-191.9) 166.3(151.7-180.8) 5-year OS rate/% 97.9 93.5 1.088 0.073 5-year CSS rate/% 100 97.8 1.032 0.310 Tumor size ≤10 mm n=57 n=59 OS(95%CI)/month 182.9(174.1-191.8) 159.7(145.3-174.1) 5-year OS rate/% 96.4 91.1 1.261 0.065 5-year CSS rate/% 100 98.3 0.975 0.324 11-20 mm* n=9 n=7 5-year OS rate/% 100 100 0 1.000 5-year CSS rate/% 100 100 0 1.000 SMI No n=31 n=32 OS(95%CI)/month 180.0(167.8-192.1) 159.2(140.3-178.1) 5-year OS rate/% 96.7 89.8 1.001 0.190 5-year CSS rate/% 100 100 0 1.000 Yes n=35 n=34 OS(95%CI)/month 186.8(178.6-194.9) 165.0(147.5-182.5) 5-year OS rate/% 97.0 93.9 0.380 0.190 5-year CSS rate/% 100 100 1.045 0.030 *5-year OS rate and 5-year CSS rate were all 100%, so the survival curve was not drawn. OS: overall survival; CSS: cancer-specific survival; SMI: submucosal involvement.
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