Prognostic significance of adjuvant chemotherapy in patients with gastric neuroendocrine carcinoma

doi:10.19401/j.cnki.1007-3639.2022.09.008

Abstract

Abstract:

Background and purpose: Gastric neuroendocrine neoplasm (NEN) is a rare type of gastric malignant tumors. According to the 2019 World Health Organization (WHO) classification criteria for gastrointestinal NEN, gastric NEN can be divided into well-differentiated neuroendocrine tumor (NET) and poorly-differentiated neuroendocrine carcinoma (NEC). At present, there is a lack of research on the prognosis of adjuvant chemotherapy for gastric NEC (GNEC). The aim of the research was to investigate whether adjuvant chemotherapy can benefit patients with GNEC and provide a basis for clinical decision-making. Methods: A retrospective analysis was performed on the clinical data of about 184 patients with GNEC from July 2008 to June 2019 in Sun Yat-sen University Cancer Center, The First Affiliated Hospital of Sun Yat-sen University and Fudan University Shanghai Cancer Center. The follow-up deadline was May 31, 2022. Kaplan-Meier method was used to draw the survival curve, and prognostic relevant factors affecting the survival of patients with GNEC and the independent prognostic factors were screened out according to univariate and multivariate COX regression analyses. Finally, the effects of chemotherapy and surgery on the prognosis of patients were further analyzed. The test level was α = 0.05, and SPSS 25.0 was used for all statistical analyses. Results: By univariate COX regression analysis, it was found that surgery, chemotherapy, treatment method, N stage, M stage and TNM stage were the variables affecting the prognosis of patients with GNEC (P<0.05). Multivariable COX regression analysis results showed that surgery, chemotherapy and M stage were independent prognostic factors for survival in patients with GNEC (P<0.001). The 3-year cumulative survival rates of TNM stage Ⅰ, Ⅱ, Ⅲ and Ⅳ were 51.9%, 55.8%, 40.7% and 23.6%, respectively. In the radical resection group, adjuvant chemotherapy could improve the prognosis of patients with GNEC (P=0.008). The 3-year cumulative survival rates of adjuvant chemotherapy group and non-adjuvant chemotherapy group were 58.8% and 33.3%, respectively. Stratified analysis showed that adjuvant chemotherapy could benefit the prognosis of patients with TNM stage Ⅱ (P = 0.018) and TNM stage Ⅲ (P = 0.023). In addition, there was no significant difference in prognosis between the first-line chemotherapy regimen [etoposide plus cisplatin (EP), irinotecan plus cisplatin (IP)] and the gastric adenocarcinoma regimen [oxaliplatin plus capecitabine (XELOX), oxaliplatin plus tegafur (SOX), oxaliplatin plus 5-fluorouracil (FOLFOX)] (P = 0.668). Conclusion: Adjuvant chemotherapy can significantly improve the prognosis of patients with GNEC, providing a reference for clinical decision-making.

Key words: Gastric neuroendocrine carcinoma, Adjuvant chemotherapy, Prognosis

CLC Number:

R735.2

ZHANG Rihong, GUO Yu, LIANG Yun, CHEN Luohai, CHEN Jie, WANG Wei. Prognostic significance of adjuvant chemotherapy in patients with gastric neuroendocrine carcinoma[J]. China Oncology, 2022, 32(9): 807-817.

Figures/Tables 6

Tab. 1

Tab. 2

Results of univariate and multivariate analysis"

Variable	Univariate analysis		Multivariate analysis
Variable	HR (95% CI)	P value	HR (95% CI)	P value
Age/year		0.154
<60	1.000
≥60	1.365 (0.890-2.094)
Gender		0.784
Male	1.000
Female	1.067 (0.672-1.694)
Tumor site		0.774
Upper stomach	1.000
Middle stomach	0.861 (0.560-1.324)	0.496
Lower stomach	1.000 (0.607-1.648)	0.998
Tumor size/cm		0.311
<6	1.000
≥6	1.337 (0.762-2.347)
NA
Tumor pathological type		0.259
NEC	1.000
MiNEN	1.267 (0.840-1.910)
Histopathology		0.891
Large cell	1.000
Small cell	0.876 (0.489-1.571)	0.658
Mixed	0.894 (0.518-1.543)	0.687
Ki-67 proliferation index		0.141
20%-55%	1.000
>55%	1.379 (0.899-2.115)
T stage		0.255
T₁	1.000
T₂	1.153 (0.312-4.268)	0.831
T₃	2.055 (0.644-6.559)	0.224
T₄	2.064 (0.629-6.773)	0.232
N stage		0.029	1.145 (0.898-1.461)	0.276
N₀	1.000
N₁	1.062 (0.657-1.717)	0.805
N₂	0.783 (0.350-1.752)	0.552
N₃	2.457 (1.230-4.911)	0.011
M stage		<0.001	2.754 (1.703-4.454)	<0.001
M₀	1.000
M₁	2.818 (1.938-4.098)
TNM stage		<0.001
Ⅰ	1.000
Ⅱ	1.717 (0.604-4.879)	0.310
Ⅲ	2.170 (0.754-6.241)	0.151
Ⅳ	5.047 (1.821-13.989)	0.002
Surgery		<0.001	0.378 (0.229-0.626)	<0.001
No	1.000
Yes	0.224 (0.149-0.339)
Surgery mode		0.153
Radical surgery	1.000
Palliative surgery	1.844 (0.797-4.267)
Chemotherapy		<0.001	0.347 (0.215-0.559)	<0.001
No	1.000
Yes	0.481 (0.319-0.726)
Chemotherapy regimen		0.836
EP, IP	1.000
XELOX, SOX, FOLFOX	0.889 (0.520-1.520)	0.668
FOLFIRI, CAPTEM, taxol	0.719 (0.174-2.967)	0.648
Severe adverse reactions to chemotherapy occurred		0.736
No	1.000
Yes	0.923 (0.580-1.470)
Comprehensive treatment model		<0.001
Surgery+chemotherapy	1.000
Surgery alone	2.120 (1.273-3.529)	0.004
Chemotherapy alone	4.476 (2.783-7.197)	<0.001
Without treatment	14.693 (7.083-30.479)	<0.001

Tab. 2

Fig. 1

Tab. 3

Fig. 2

Fig. 3

References 12

[1]	NAGTEGAAL I D, ODZE R D, KLIMSTRA D, et al. The 2019 WHO classification of tumours of the digestive system[J]. Histopathology, 2020, 76(2): 182-188. doi: 10.1111/his.13975 pmid: 31433515
[2]	LIN J X, ZHAO Y J, ZHOU Y B, et al. Comparison of survival and patterns of recurrence in gastric neuroendocrine carcinoma, mixed adenoneuroendocrine carcinoma, and adenocarcinoma[J]. JAMA Netw Open, 2021, 4(7): e2114180.
[3]	GARCIA-CARBONERO R, SORBYE H, BAUDIN E, et al. ENETS consensus guidelines for high-grade gastroenteropancreatic neuroendocrine tumors and neuroendocrine carcinomas[J]. Neuroendocrinology, 2016, 103(2): 186-194. doi: 10.1159/000443172
[4]	LIU D J, FU X L, LIU W, et al. Clinicopathological, treatment, and prognosis study of 43 gastric neuroendocrine carcinomas[J]. World J Gastroenterol, 2017, 23(3): 516-524. doi: 10.3748/wjg.v23.i3.516
[5]	HAN D, LI Y L, ZHOU Z W, et al. Clinicopathological characteristics and prognosis of 232 patients with poorly differentiated gastric neuroendocrine neoplasms[J]. World J Gastroenterol, 2021, 27(21): 2895-2909. doi: 10.3748/wjg.v27.i21.2895
[6]	LIN J P, ZHAO Y J, HE Q L, et al. Adjuvant chemotherapy for patients with gastric neuroendocrine carcinomas or mixed adenoneuroendocrine carcinomas[J]. Br J Surg, 2020, 107(9): 1163-1170. doi: 10.1002/bjs.11608
[7]	XIE J W, LU J, WANG J B, et al. Prognostic factors for survival after curative resection of gastric mixed adenoneuroendocrine carcinoma: a series of 80 patients[J]. BMC Cancer, 2018, 18(1): 1021. doi: 10.1186/s12885-018-4943-z
[8]	KIM B S, PARK Y S, YOOK J H, et al. Comparison of the prognostic values of the 2010 WHO classification, AJCC 7th edition, and ENETS classification of gastric neuroendocrine tumors[J]. Medicine, 2016, 95(30): e3977. doi: 10.1097/MD.0000000000003977
[9]	张剑, 臧凤琳, 张家丽, 等. 分化差的胃神经内分泌肿瘤预后分析[J]. 肿瘤防治研究, 2019, 46(5): 447-451.
	ZHANG J, ZANG F L, ZHANG J L, et al. Prognosis of poorly-differentiated gastric neuroendocrine neoplasm[J]. Cancer Res Prev Treat, 2019, 46(5): 447-451.
[10]	PARK J Y, RYU M H, PARK Y S, et al. Prognostic significance of neuroendocrine components in gastric carcinomas[J]. Eur J Cancer, 2014, 50(16): 2802-2809. doi: 10.1016/j.ejca.2014.08.004 pmid: 25201164
[11]	中华医学会消化病学分会胃肠激素与神经内分泌肿瘤学组. 胃肠胰神经内分泌肿瘤诊治专家共识(2020·广州)[J]. 中华消化杂志, 2021, 41(2): 76-87.
	Gastrointestinal Hormone and Neuroendocrine Neoplasm Group, Chinese Society of Gastroenterology, Chinese Medical Association. Expert consensus on diagnosis and treatment of gastroenteropancreatic neuroendocrine neoplasm (2020, Guangzhou)[J]. Chin J Dig, 2021, 41(2): 76-87.
[12]	中国抗癌协会神经内分泌肿瘤专业委员会. 中国抗癌协会神经内分泌肿瘤诊治指南(2022年版)[J]. 中国癌症杂志, 2022, 32(6): 545-580.
	Society of Neuroendocrine Neoplasm of China Anti-Cancer Association. China Anti-Cancer Association guideline for diagnosis and treatment of neuroendocrine neoplasm (2022 edition)[J]. China Oncol, 2022, 32(6): 545-580.

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[2]	CAO Mengxuan, HU Can, ZHANG Yanqiang, HUANG Ling, DU Yian, YU Pengcheng, ZHANG Ruolan, XU Zhiyuan, CHENG Xiangdong. Analysis of risk factors of early recurrence and metastasis after radical resection of gastric cancer [J]. China Oncology, 2022, 32(7): 588-595.
[3]	QIAN Yao, LIU Feng. Research progress and prospects of neoadjuvant endocrine therapy for breast cancer [J]. China Oncology, 2022, 32(7): 643-649.
[4]	LIU Yanquan, HU Xiaomei, YIN Yue, LIN Lin, SHEN Jianzhen, CHEN Yuting, TANG Huanwen. A retrospective study and clinical analysis of post-transplant lymphoproliferative disorder [J]. China Oncology, 2022, 32(7): 650-656.
[5]	QU Yiping, HOU Peng. Genetic characteristics and prognosis of metastatic thyroid cancer in children [J]. China Oncology, 2022, 32(5): 373-379.
[6]	MA Guang, OU Xiaomin, HU Chaosu, SONG Shaoli, YANG Zhongyi. Value of pretreatment ¹⁸F-FLT PET/CT and ¹⁸F-FDG PET/CT uptake heterogeneity for early prediction of treatment outcome in locally advanced nasopharyngeal carcinoma [J]. China Oncology, 2022, 32(4): 309-315.
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[8]	WANG Zimao, CAO Yuan, WANG Qiying. Construction and validation of the survival prediction model for patients with cutaneous spindle cell melanoma [J]. China Oncology, 2022, 32(3): 234-242.
[9]	CHEN Xi, ZENG Xiaoying, CHEN Jiayan, LIU Fei, TANG Xi. The clinical value of mismatch repair protein combined with serum tumor markers and Ki-67 proliferation index in the prognostic evaluation of colorectal cancer [J]. China Oncology, 2022, 32(3): 243-250.
[10]	HOU Qinghua, ZHONG Yanfeng, LIU Linzhuang, WU Liusheng, LIU Jixian. Expression, prognostic value of CBX3 in lung adenocarcinoma and its effect on biological behavior of cancer cells [J]. China Oncology, 2022, 32(2): 152-160.
[11]	MA Yifei , LIANG Xinjun , WEI Shaozhong . Prognostic value of inflammatory and immune markers in resectable colorectal cancer [J]. China Oncology, 2021, 31(9): 845-851.
[12]	LEI Yajie , GAO Yi , WANG Zhijie , CHENG Xi , YANG Yufei , ZHOU Hongyu , CHEN Lihua , CHEN Yixin , LI Haoran , LI Ziting , WU Xiaohua . Potential role of lymphadenectomy in patients with ovarian cancer (ⅠC-ⅡA): a retrospective trial [J]. China Oncology, 2021, 31(8): 740-745.
[13]	GAO Heli, XU Jin, YU Xianjun. Advances in clinical diagnosis and treatment of gastroenteropancreatic neuroendocrine tumor G3 [J]. China Oncology, 2021, 31(7): 567-573.
[14]	GONG Runze, HU Haiyan. Clinical significance of CCL2 expression in osteosarcoma tissue [J]. China Oncology, 2021, 31(6): 455-459.
[15]	PENG Zishan, KONG Hui, BAO Zhen, ZHAO Hongxing, LIU Xin, LU Shaohua. Clinicopathological analysis of 83 cases of multifocal lung adenocarcinoma [J]. China Oncology, 2021, 31(5): 408-418.