Construction and validation of prediction model for pathological complete response of patients with advanced gastric cancer after neoadjuvant chemotherapy

doi:10.3877/cma.j.issn.1674-0793.2021.04.009

Abstract

Abstract:

Objective

To analyze the influencing factors of pathological complete response (pCR) in patients with advanced gastric cancer (AGC) after neoadjuvant chemotherapy, and to construct a nomogram prediction model of pCR.

Methods

The clinical data of 249 patients with AGC admitted to Special Medical Center of Armed Police Force and Beijing General Team Hospital of People’s Armed Police Force fromJanuary 2012 to December 2019 were collected. Logistic regression analysis was used to determine the risk factors of pCR after neoadjuvant chemotherapy. Based on the risk factors, a nomogram model was constructed to predict pCR in patients with AGC after neoadjuvant chemotherapy, and Bootstrap method was used for internal validation.

Results

A total of 33 cases (13.25%) developed pCR after neoadjuvant chemotherapy. Multivariate logistic regression analysis showed that higher CEA level, higher lymphocyte proportion, lower monocyte count and lower tumor differentiation were the influencing factors of pCR in patients with AGC after neoadjuvant chemotherapy. The accuracy of the model was verified by Bootstrap method, the C-index was 0.819 (95% CI: 0.743-0.897).

Conclusion

The nomogram constructed in this study can be used to predict the pCR of neoadjuvant chemotherapy in patients with AGC, which is worthy of clinical promotion.

Key words: Gastric neoplasms, Neoadjuvant chemotherapy, Nomogram, Pathological complete remission

Yun Zhang, Ruikui Zhang, Na Shi, Xiaona Wang, Tiantian Cao, Dongyu Zhao. Construction and validation of prediction model for pathological complete response of patients with advanced gastric cancer after neoadjuvant chemotherapy[J]. Chinese Archives of General Surgery(Electronic Edition), 2021, 15(04): 282-287.

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References 20

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项目		未缓解组	缓解组	U/χ²值	P值
例数		216	33
性别[例(%)]				1.291	0.256
	男	164(75.93)	28(84.85)
	女	52(24.07)	5(15.15)
年龄(岁)		58(51,65)	59(50,64)	0.577^a	0.627
体质指数(kg/m²)		22.26±2.87	22.35±3.51	0.163	0.871
肿瘤位置[例(%)]				5.957	0.114
食管胃交界处		62(28.70)	12(36.36)
	胃上1/3	24(11.11)	6(18.18)
	胃中1/3	51(23.61)	2(6.06)
	胃下1/3	79(36.57)	13(39.39)
肿瘤分化程度[例(%)]				12.417	0.015
	良好	5(2.31)	4(12.12)
	中分化	55(25.46)	11(33.33)
	中-低分化	27(12.50)	7(21.21)
	低分化	102(47.22)	10(30.30)
	印戒细胞癌	27(12.50)	1(3.03)
T分期[例(%)]				0.770	0.678
	T₃	106(49.07)	18(54.55)
	T_4a	89(41.20)	11(33.33)
	T_4b	21(9.72)	4(12.12)
N分期[例(%)]				0.780	0.377
	N₀	5(2.31)	0(0.00)
	N₊	211(97.69)	33(100)
白细胞(×10⁹/L)		6.49±1.92	5.87±1.48	1.775	0.077
红细胞(×10¹²/L)		4.41(3.92,4.73)	4.23(3.71,4.49)	1.823^a	0.265
中性粒细胞(×10⁹/L)		3.84(2.88,4.99)	3.07(2.59,3.60)	0.663^a	0.591
中性粒细胞比例		0.63±0.12	0.59±0.09	1.836	0.068
淋巴细胞×(10⁹/L)		1.62(1.23,2.07)	1.70(1.43,2.09)	2.922^*a	0.124
淋巴细胞比例		0.25(0.22,0.35)	0.31(0.27,0.36)	9.897^a	0.001
单核细胞(×10⁹/L)		0.52(0.42,0.63)	0.45(0.33,0.56)	5.979^a	0.015
单核细胞比例		0.08(0.06,0.11)	0.08(0.07,0.09)	1.775^a	0.274
嗜酸性粒细胞(×10⁹/L)		0.14(0.09,0.20)	0.15(0.07,0.21)	0.870^a	0.512
嗜酸性粒细胞比例		0.02(0.01,0.03)	0.03(0.02,0.04)	3.791^a	0.068
嗜碱性粒细胞(×10⁹/L)		0.03(0.02,0.04)	0.04(0.02,0.05)	0.837^a	0.524
嗜碱性粒细胞比例		0.01(0.00,0.01)	0.01(0.00,0.01)	1.723^a	0.284
血红蛋白(g/L)		124(98.35,136.02)	119(83.11,135.17)	1.348^a	0.368
血小板(×10⁹/L)		260(213.08,331.25)	262(201.72,356.54)	0.152^a	0.841
血尿酸(μmol/L)		344(261.90,415.32)	405.31(341.05,480.16)	8.894^a	0.002
血肌酐(μmol/L)		77.32(64.88,89.01)	81.09(75.35,89.51)	2.535^a	0.162
ALT(U/L)		13.79(9.91,19.02)	14.28(9.69,18.38)	0.039^a	0.960
AST(U/L)		18.52(14.84,22.11)	17.02(13.39,22.31)	1.404^a	0.354
r-GT(U/L)		18.84(14.59,30.61)	18.57(15.06,34.68)	0.395^a	0.711
总蛋白(g/L)		67.95±6.48	70.11±6.29	1.790	0.075
ALB (g/L)		39.62±4.53	41.18±3.64	1.886	0.060
碱性磷酸酶(U/L)		85.57(68.73~100.52)	77.38(58.98,90.77)	2.526^a	0.163
前白蛋白(g/L)		0.23±0.07	0.21±0.06	1.556	0.121
TBIL(μmol/L)		11.14(8.87,14.42)	10.51(6.88,16.17)	1.290^a	0.383
DBIL(μmol/L)		2.23(1.70,3.13)	2.07(1.45,3.01)	1.791^a	0.271
乳酸脱氢酶(U/L)		168(147.78,191.34)	169(149.25,197.53)	0.472^a	0.674
胆固醇(mmol/L)		4.74±1.12	5.13±1.05	1.878	0.062
三酰甘油(mmol/L)		1.06(0.85,1.37)	1.17(0.83,1.49)	0.589^a	0.622
高密度脂蛋白(mmol/L)		1.15(0.96,1.35)	1.23(1.04,1.43)	3.631^a	0.076
低密度脂蛋白(mmol/L)		2.96(2.49,3.48)	3.27(2.90,3.53)	3.575^a	0.079
C反应蛋白(mg/L)		2.36(0.93,9.68)	2.16(0.85,5.87)	1.167^a	0.417
CA125(U/mL)		15.13(9.54,24.64)	12.45(7.45,21.03)	1.372^a	0.362
CEA(μg/L)		2.52(1.37,4.92)	8.05(2.35,26.43)	8.862^a	0.002
CA19-9(U/ml)		8.85(2.43,47.48)	15.29(4.43,34.21)	1.653^a	0.298
CA153(U/ml)		7.38(5.27,10.75)	8.28(6.16,11.87)	1.582^a	0.313
AFP(μg/L)		2.65(1.86,4.20)	2.77(2.04,10.76)	0.728^a	0.565
化疗方案[例(%)]				3.286	0.070
	mFLOT	121(56.02)	24(72.73)
	SOX/FOLFOX/XELOX	95(43.98)	9(27.27)
化疗周期		4(4,5)	4(4,4)	0.192^a	0.818

项目		未缓解组	缓解组	U/χ²值	P值
例数		216	33
性别[例(%)]				1.291	0.256
	男	164(75.93)	28(84.85)
	女	52(24.07)	5(15.15)
年龄(岁)		58(51,65)	59(50,64)	0.577^a	0.627
体质指数(kg/m²)		22.26±2.87	22.35±3.51	0.163	0.871
肿瘤位置[例(%)]				5.957	0.114
食管胃交界处		62(28.70)	12(36.36)
	胃上1/3	24(11.11)	6(18.18)
	胃中1/3	51(23.61)	2(6.06)
	胃下1/3	79(36.57)	13(39.39)
肿瘤分化程度[例(%)]				12.417	0.015
	良好	5(2.31)	4(12.12)
	中分化	55(25.46)	11(33.33)
	中-低分化	27(12.50)	7(21.21)
	低分化	102(47.22)	10(30.30)
	印戒细胞癌	27(12.50)	1(3.03)
T分期[例(%)]				0.770	0.678
	T₃	106(49.07)	18(54.55)
	T_4a	89(41.20)	11(33.33)
	T_4b	21(9.72)	4(12.12)
N分期[例(%)]				0.780	0.377
	N₀	5(2.31)	0(0.00)
	N₊	211(97.69)	33(100)
白细胞(×10⁹/L)		6.49±1.92	5.87±1.48	1.775	0.077
红细胞(×10¹²/L)		4.41(3.92,4.73)	4.23(3.71,4.49)	1.823^a	0.265
中性粒细胞(×10⁹/L)		3.84(2.88,4.99)	3.07(2.59,3.60)	0.663^a	0.591
中性粒细胞比例		0.63±0.12	0.59±0.09	1.836	0.068
淋巴细胞×(10⁹/L)		1.62(1.23,2.07)	1.70(1.43,2.09)	2.922^*a	0.124
淋巴细胞比例		0.25(0.22,0.35)	0.31(0.27,0.36)	9.897^a	0.001
单核细胞(×10⁹/L)		0.52(0.42,0.63)	0.45(0.33,0.56)	5.979^a	0.015
单核细胞比例		0.08(0.06,0.11)	0.08(0.07,0.09)	1.775^a	0.274
嗜酸性粒细胞(×10⁹/L)		0.14(0.09,0.20)	0.15(0.07,0.21)	0.870^a	0.512
嗜酸性粒细胞比例		0.02(0.01,0.03)	0.03(0.02,0.04)	3.791^a	0.068
嗜碱性粒细胞(×10⁹/L)		0.03(0.02,0.04)	0.04(0.02,0.05)	0.837^a	0.524
嗜碱性粒细胞比例		0.01(0.00,0.01)	0.01(0.00,0.01)	1.723^a	0.284
血红蛋白(g/L)		124(98.35,136.02)	119(83.11,135.17)	1.348^a	0.368
血小板(×10⁹/L)		260(213.08,331.25)	262(201.72,356.54)	0.152^a	0.841
血尿酸(μmol/L)		344(261.90,415.32)	405.31(341.05,480.16)	8.894^a	0.002
血肌酐(μmol/L)		77.32(64.88,89.01)	81.09(75.35,89.51)	2.535^a	0.162
ALT(U/L)		13.79(9.91,19.02)	14.28(9.69,18.38)	0.039^a	0.960
AST(U/L)		18.52(14.84,22.11)	17.02(13.39,22.31)	1.404^a	0.354
r-GT(U/L)		18.84(14.59,30.61)	18.57(15.06,34.68)	0.395^a	0.711
总蛋白(g/L)		67.95±6.48	70.11±6.29	1.790	0.075
ALB (g/L)		39.62±4.53	41.18±3.64	1.886	0.060
碱性磷酸酶(U/L)		85.57(68.73~100.52)	77.38(58.98,90.77)	2.526^a	0.163
前白蛋白(g/L)		0.23±0.07	0.21±0.06	1.556	0.121
TBIL(μmol/L)		11.14(8.87,14.42)	10.51(6.88,16.17)	1.290^a	0.383
DBIL(μmol/L)		2.23(1.70,3.13)	2.07(1.45,3.01)	1.791^a	0.271
乳酸脱氢酶(U/L)		168(147.78,191.34)	169(149.25,197.53)	0.472^a	0.674
胆固醇(mmol/L)		4.74±1.12	5.13±1.05	1.878	0.062
三酰甘油(mmol/L)		1.06(0.85,1.37)	1.17(0.83,1.49)	0.589^a	0.622
高密度脂蛋白(mmol/L)		1.15(0.96,1.35)	1.23(1.04,1.43)	3.631^a	0.076
低密度脂蛋白(mmol/L)		2.96(2.49,3.48)	3.27(2.90,3.53)	3.575^a	0.079
C反应蛋白(mg/L)		2.36(0.93,9.68)	2.16(0.85,5.87)	1.167^a	0.417
CA125(U/mL)		15.13(9.54,24.64)	12.45(7.45,21.03)	1.372^a	0.362
CEA(μg/L)		2.52(1.37,4.92)	8.05(2.35,26.43)	8.862^a	0.002
CA19-9(U/ml)		8.85(2.43,47.48)	15.29(4.43,34.21)	1.653^a	0.298
CA153(U/ml)		7.38(5.27,10.75)	8.28(6.16,11.87)	1.582^a	0.313
AFP(μg/L)		2.65(1.86,4.20)	2.77(2.04,10.76)	0.728^a	0.565
化疗方案[例(%)]				3.286	0.070
	mFLOT	121(56.02)	24(72.73)
	SOX/FOLFOX/XELOX	95(43.98)	9(27.27)
化疗周期		4(4,5)	4(4,4)	0.192^a	0.818

项目	未缓解组(216例)	缓解组(33例)	χ²值	P值
腹腔脓肿	32 (14.81)	4 (12.12)	0.168	0.682
吻合口瘘	11 (5.09)	1 (3.03)	0.265	0.606
十二指肠残端漏	1 (0.46)	1 (3.03)	2.368	0.124
其他漏	9 (4.17)	1 (3.03)	0.096	0.757
出血	5 (2.31)	0 (0)	0.780	0.377
腹腔内出血	4 (1.85)	0 (0)	0.621	0.431
吻合口出血	1 (0.46)	0 (0)	0.153	0.695
肺炎	12 (5.56)	3 (9.09)	0.632	0.427
胰瘘	3 (1.39)	1 (3.03)	0.488	0.485
梗阻	2 (0.93)	1 (3.03)	1.065	0.302
腹泻	3 (1.39)	0 (0)	0.464	0.496
二次手术	1 (0.46)	1 (3.03)	2.368	0.124
出院前死亡	1 (0.46)	0 (0)	0.153	0.695

项目	未缓解组(216例)	缓解组(33例)	χ²值	P值
腹腔脓肿	32 (14.81)	4 (12.12)	0.168	0.682
吻合口瘘	11 (5.09)	1 (3.03)	0.265	0.606
十二指肠残端漏	1 (0.46)	1 (3.03)	2.368	0.124
其他漏	9 (4.17)	1 (3.03)	0.096	0.757
出血	5 (2.31)	0 (0)	0.780	0.377
腹腔内出血	4 (1.85)	0 (0)	0.621	0.431
吻合口出血	1 (0.46)	0 (0)	0.153	0.695
肺炎	12 (5.56)	3 (9.09)	0.632	0.427
胰瘘	3 (1.39)	1 (3.03)	0.488	0.485
梗阻	2 (0.93)	1 (3.03)	1.065	0.302
腹泻	3 (1.39)	0 (0)	0.464	0.496
二次手术	1 (0.46)	1 (3.03)	2.368	0.124
出院前死亡	1 (0.46)	0 (0)	0.153	0.695

影响因素	β	SE	Wald值	P值	OR	95% CI
肿瘤分化程度^a	-0.431	0.21	4.295	0.048	0.65	0.431~0.981
单核细胞计数(×10⁹/L)	-0.315	0.09	4.634	0.038	0.73	0.612~0.871
CEA(μg/L)	0.451	0.09	8.894	0.002	1.57	1.316~1.873
淋巴细胞比例	0.077	0.03	8.307	0.003	1.08	1.018~1.145

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