Nomograms for predicting pathological response to neoadjuvant treatments in patients with rectal cancer

doi:10.3748/wjg.v25.i1.118

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World Journal of Gastroenterology

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Retrospective Study

World J Gastroenterol. Jan 7, 2019; 25(1): 118-137
Published online Jan 7, 2019. doi: 10.3748/wjg.v25.i1.118

Table 1 Predictive factors for complete pathological response in univariate logistic regression analysis for all patients

Variable		Non-pCR (n = 331) n P₅₀ (P₂₅-P₇₅)	pCR (n = 72) n P₅₀ (P₂₅-P₇₅)	pCR rate	P-value
Gender	Male	232	49	17.44%	0.653
Gender	Female	96	23	19.33%	0.653
Age (yr)	≤ 60	210	54	20.45%	0.07
Age (yr)	> 60	119	18	13.14%	0.07
BMI (kg/cm²)	< 25	231	53	18.66%	0.581
BMI (kg/cm²)	≥ 25	78	15	16.13%	0.581
Hemoglobin (g/L)	≤ 125	109	16	12.80%	0.126
Hemoglobin (g/L)	> 125	172	41	19.25%	0.126
NLR	> 3	37	11	22.92%	0.227
NLR	≤ 3	244	46	15.86%	0.227
Platelet (× 10⁹/L)		237.5 (200.25-286.75)	246 (200.5-268.5)		0.981
ApoA1 (g/L)		1.29 (1.13-1.44)	1.3 (1.15-1.52)		0.454
ApoB (g/L)		0.98 (0.79-1.14)	0.97 (0.82-1.19)		0.382
The interval (d)		39 (22.25-54)	50 (42-56.5)		0
CEA (ng/mL)	> 5	163	28	14.66%	0.217
CEA (ng/mL)	≤ 5	118	29	19.73%	0.217
Differentiation	Moderate-poor	274	44	13.84%	0.001
Differentiation	Well	44	20	31.25%	0.001
DTAV (cm)	< 5	140	41	22.65%	0.024
DTAV (cm)	≥ 5	191	31	13.96%	0.024
TL (cm)	> 3	237	41	14.75%	0.001
TL (cm)	≤ 3	73	30	29.13%	0.001
TCE	< 50%	37	7	15.91%	0.772
TCE	≥ 50%	256	55	17.68%	0.772
cT	2	16	5	23.81%	0.405
	3	234	56	19.31%
	4	54	8	12.90%
cN	+	235	57	19.52%	0.465
cN	-	78	15	16.13%	0.465
MRF	-	231	61	20.89%	0.013
MRF	+	97	11	10.19%	0.013
NT regimen	Capecitabine/de Gramont-RT	102	13	11.30%	0
	mFOLFOX6	148	14	8.64%
	mFOLFOX6-RT	81	45	35.71%

Platelet, apolipoprotein A-1, apolipoprotein B, and the interval were calculated as metrological data, and others are counting data. pCR: Complete pathological response; NLR: Neutrophil-lymphocyte ratio; DTAV: Distance of tumor from the anal verge; TL: Tumor length; TCE: Tumor circumferential extent; NT: Neoadjuvant therapy; PLT: Platelet; ApoA1: Apolipoprotein A-1; ApoB: Apolipoprotein B; MRF: Mesorectal fascia; CEA: Carcinoembryonic antigen.

Table 2 Predictive factors for complete pathological response in multivariate logistic regression analysis for all patients

Variable		P-value	OR	95%CI
Age (yr)	≤ 60	0.703	0.873	0.434-1.756
Age (yr)	> 60		1
Differentiation	Well	0.003	2.966	1.449-6.069
Differentiation	Moderate-poor		1
TL (cm)	≤ 3	0.004	2.608	1.347-5.052
TL (cm)	> 3		1
DTAV	≥ 5	0.07	0.56	0.299-1.049
DTAV	< 5		1
MRF	-	0.017	2.729	1.199-6.211
MRF	+		1
NT regimen	mFOLFOX6-RT	0	5.339	2.394-11.903
	mFOLFOX6	0.402	1.821	0.449-7.387
	Capecitabine/de Gramont-RT		1
The interval		0.093	1.029	0.995-1.064

pCR: Complete pathological response; TL: Tumor length; DTAV: Distance of tumor from the anal verge; NT: Neoadjuvant therapy; MRF: Mesorectal fascia.

Table 3 Predictive factors for good downstaging in univariate logistic regression analysis for all patients

Variable		Bad downstaging (n = 226) n P₅₀ (P₂₅-P₇₅)	Good downstaging (n = 177) n P₅₀ (P₂₅-P₇₅)	Good downstaging rate	P-value
Gender	Male	164	117	41.64%	0.106
Gender	Female	59	60	50.42%	0.106
Age (yr)	≤ 60	144	120	45.45%	0.462
Age (yr)	> 60	80	57	41.61%	0.462
BMI (kg/cm²)	< 25	159	125	44.01%	0.475
BMI (kg/cm²)	≥ 25	56	37	39.78%	0.475
Hemoglobin (g/L)	≤ 125	69	56	44.80%	0.426
Hemoglobin (g/L)	> 125	127	86	40.38%	0.426
NLR	> 3	27	21	43.75%	0.792
NLR	≤ 3	169	121	41.72%	0.792
Platelet (×10⁹/L)		241 (207-294)	236 (193-272.25)		0.125
ApoA1 (g/L)		1.27 (1.13-1.44)	1.31 (1.15-1.48)		0.228
ApoB (g/L)		0.98 (0.79-1.13)	0.97 (0.79-1.18)		0.88
The interval		39 (23-54)	48 (25.75-55)		0.062
CEA (ng/mL)	> 5	125	66	34.55%	0.002
CEA (ng/mL)	≤ 5	71	76	51.70%	0.002
Differentiation	Moderate-poor	194	124	38.99%	0
Differentiation	Well	20	44	68.75%	0
DTAV (cm)	< 5	85	96	53.04%	0.001
DTAV (cm)	≥ 5	141	81	36.49%	0.001
TL (cm)	> 3	167	111	39.93%	0.002
TL (cm)	≤ 3	44	59	57.28%	0.002
TCE	< 50%	23	21	47.73%	0.508
TCE	≥ 50%	179	132	42.44%	0.508
cT	2	4	17	80.95%	0
	3	160	130	44.83%
	4	46	16	25.81%
cN	+	166	126	43.15%	0.074
cN	-	43	50	53.76%	0.074
MRF	-	142	150	51.37%	0
MRF	+	81	27	25.00%	0
NT regimen	Capecitabine/de Gramont-RT	64	51	44.35%	0.061
	mFOLFOX6-RT	61	65	51.59%
	mFOLFOX6	101	61	37.65%

Platelet, apolipoprotein A-1, apolipoprotein B, and the interval were calculated as metrological data, and others are counting data. NLR: Neutrophil-lymphocyte ratio; DTAV: Distance of tumor from the anal verge; TL: Tumor length; TCE: Tumor circumferential extent; NT: Neoadjuvant therapy; PLT: Platelet; ApoA1: Apolipoprotein A-1; ApoB: Apolipoprotein B; MRF: Mesorectal fascia; CEA: Carcinoembryonic antigen.

Table 4 Predictive factors for good downstaging in multivariate logistic regression analysis for all patients

Variable		P-value	OR	95%CI
CEA (ng/mL)	≤ 5	0.095	1.565	0.925-2.647
CEA (ng/mL)	> 5		1
Differentiation	Well	0	4.814	2.343-9.892
Differentiation	Moderate-poor		1
DTAV (cm)	≥ 5	0.052	0.588	0.345-1.004
DTAV (cm)	< 5		1
TL (cm)	≤ 3	0.9	1.04	0.566-1.909
TL (cm)	> 3		1
cT	3	0.046	0.248	0.063-0.974
	4	0.127	0.282	0.056-1.434
	2		1
MRF	-	0	4.226	1.894-9.426
MRF	+		1

DTAV: Distance of tumor from the anal verge; TL: Tumor length; MRF: Mesorectal fascia; CEA: Carcinoembryonic antigen.

Table 5 Distribution of pretreatment clinical parameters in different neoadjuvant therapy regimen groups

Variable		Capecitabine/deGramont-RT n (%) P₅₀ (P₂₅-P₇₅)	mFOLFOX6 n (%) P₅₀ (P₂₅-P₇₅)	mFOLFOX6-RT n (%) P₅₀ (P₂₅-P₇₅)	P-value
Gender	Male	76 (66.67)	107 (66.88)	98 (77.78)	0.083
Gender	Female	38 (33.33)	53 (33.13)	28 (22.22)
Age (yr)	≤ 60	66 (57.39)	102 (63.75)	96 (76.19)	0.007
Age (yr)	> 60	49 (42.61)	58 (36.25)	30 (23.81)	0.007
BMI (kg/cm²)	< 25	83 (76.85)	118 (76.62)	83 (72.17)	0.641
BMI (kg/cm²)	≥ 25	25 (23.15)	36 (23.38)	32 (27.83)	0.641
Hemoglobin (g/L)	≤ 125	34 (34.34)	55 (39.29)	36 (36.36)	0.729
Hemoglobin (g/L)	> 125	65 (65.66)	85 (60.71)	63 (63.64)	0.729
NLR	> 3	16 (16.16)	17 (12.14)	15 (15.15)	0.646
NLR	≤ 3	83 (83.84)	123 (87.86)	84 (84.85)	0.646
CEA (ng/mL)	> 5	56 (56.57)	79 (56.43)	56 (56.57)	1
CEA (ng/mL)	≤ 5	43 (43.43)	61 (43.57)	43 (43.43)	1
Differentiation	Moderate-poor	90 (81.08)	135 (87.1)	93 (80.17)	0.246
Differentiation	Well	21 (18.92)	20 (12.9)	23 (19.83)	0.246
DTAV (cm)	< 5	61 (53.04)	62 (38.27)	58 (46.03)	0.049
DTAV (cm)	≥ 5	54 (46.96)	100 (61.73)	68 (53.97)	0.049
TL (cm)	> 3	82 (74.55)	105 (70)	91 (75.21)	0.572
TL (cm)	≤ 3	28 (25.45)	45 (30)	30 (24.79)	0.572
TCE	< 50%	10 (10)	22 (15.28)	12 (10.81)	0.389
TCE	≥ 50%	90 (90)	122 (84.72)	99 (89.19)	0.389
cN	+	84 (75)	110 (73.33)	98 (79.67)	0.462
cN	-	28 (25)	40 (26.67)	25 (20.33)	0.462
MRF	-	85 (74.56)	119 (74.38)	88 (69.84)	0.627
MRF	+	29 (25.44)	41 (25.63)	38 (30.16)	0.627
pCR	Non-pCR	102 (88.7)	148 (91.36)	81 (64.29)	0
pCR	pCR	13 (11.3)	14 (8.64)	45 (35.71)	0
Downstaging	Bad	64 (55.65)	101 (62.35)	61 (48.41)	0.061
Downstaging	Good	51 (44.35)	61 (37.65)	65 (51.59)	0.061
cT	2	9 (8.26)	10 (6.85)	2 (1.69)	0.19
	3	85 (77.98)	112 (76.71)	93 (78.81)
	4	15 (13.76)	24 (16.44)	23 (19.49)
PLT (×10⁹/L)		230 (188.75-267.25)	236.5 (200.25-290.75)	244 (212-281)	0.168
ApoA1 (g/L)		1.31 (1.14-1.47)	1.29 (1.12-1.44)	1.28 (1.15-1.5)	0.73
ApoB (g/L)		0.97 (0.8-1.09)	0.98 (0.78-1.14)	0.98 (0.81-1.21)	0.425
The interval		54 (49-58.25)	22 (18-25.75)	52 (47-59)	0

Table 6 Predictive factors for complete pathological response in univariate logistic regression analysis for the capecitabine/deGramont-RT regimen

Variable		Non-pCR (n = 102) n P₅₀ (P₂₅-P₇₅)	pCR (n = 13) n P₅₀ (P₂₅-P₇₅)	pCR rate	P-value
Gender	Male	70	6	7.89%	0.096
Gender	Female	31	7	18.42%	0.096
Age (yr)	≤ 60	56	10	15.15%	0.131
Age (yr)	> 60	46	3	6.12%	0.131
BMI (kg/cm²)	< 25	75	8	9.64%	0.375
BMI (kg/cm²)	≥ 25	21	4	16.00%	0.375
Hemoglobin (g/L)	≤ 125	33	1	2.94%	0.087
Hemoglobin (g/L)	> 125	56	9	13.85%	0.087
NLR	> 3	12	4	25.00%	0.031
NLR	≤ 3	77	6	7.23%	0.031
PLT (×10⁹/L)		228 (188.25-266.75)	252 (188.75-319)		0.338
ApoA1 (g/L)		1.3 (1.14-1.48)	1.34 (1.11-1.46)		0.912
ApoB (g/L)		0.97 (0.8-1.09)	0.92 (0.78-1.02)		0.667
The interval		53.97 ± 8.94	52.38 ± 10.79		0.588
CEA (ng/mL)	> 5	51	5	8.93%	0.659
CEA (ng/mL)	≤ 5	38	5	11.63%	0.659
Differentiation	Moderate-poor	82	8	8.89%	0.177
Differentiation	Well	17	4	19.05%	0.177
DTAV (cm)	< 5	52	9	14.75%	0.214
DTAV (cm)	≥ 5	50	4	7.41%	0.214
TL (cm)	> 3	74	8	9.76%	0.252
TL (cm)	≤ 3	23	5	17.86%	0.252
TCE	≤ 50%	10	0	0.00%	0.241
TCE	> 50%	79	11	12.22%	0.241
cT	2	7	2	22.22%	0.521
	3	75	10	11.76%
	4	14	1	6.67%
cN	+	73	11	13.10%	0.394
cN	-	26	2	7.14%	0.394
MRF	-	74	11	12.94%	0.377
MRF	+	27	2	6.90%	0.377

Platelet, apolipoprotein A-1, apolipoprotein B, and the interval were calculated as metrological data, and others are counting data. pCR: Complete pathological response; NLR: Neutrophil-lymphocyte ratio; DTAV: Distance of tumor from the anal verge; TL: Tumor length; TCE: Tumor circumferential extent; PLT: Platelet; ApoA1: Apolipoprotein A-1; ApoB: Apolipoprotein B; MRF: Mesorectal fascia; CEA: Carcinoembryonic antigen.

Table 7 Predictive factors for complete pathological response in multivariate logistic regression analysis for the capecitabine/deGramont-RT regimen

Variable		P value	OR	95%CI
NLR	> 3	0.042	4.278	1.051-17.413
NLR	≤ 3		1

NLR: Neutrophil-lymphocyte ratio.

Table 8 Predictive factors for complete pathological response in univariate logistic regression analysis for the mFOLFOX6-RT regimen

Variable		Non-pCR (n = 81) n P₅₀ (P₂₅-P₇₅)	pCR (n = 45) n P₅₀ (P₂₅-P₇₅)	pCR rate	P-value
Gender	Male	63	35	35.71%	1
Gender	Female	18	10	35.71%	1
Age (yr)	≤ 60	62	34	35.42%	0.901
Age (yr)	> 60	19	11	36.67%	0.901
BMI (kg/cm²)	< 25	49	34	40.96%	0.202
BMI (kg/cm²)	≥ 25	23	9	28.13%	0.202
Hemoglobin (g/L)	≤ 125	23	13	36.11%	0.905
Hemoglobin (g/L)	> 125	41	22	34.92%	0.905
NLR	> 3	9	6	40.00%	0.683
NLR	≤ 3	55	29	34.52%	0.683
PLT (×10⁹/L)		246.5 (214.25-289.75)	239 (197-269)		0.22
ApoA1 (g/L)		1.26 (1.15-1.44)	1.3 (1.15-1.55)		0.453
ApoB (g/L)		1 (0.81-1.24)	0.97 (0.81-1.17)		0.725
The interval		51.5 (43-58.75)	54 (50-62)		0.116
CEA (ng/mL)	> 5	40	16	28.57%	0.107
CEA (ng/mL)	≤ 5	24	19	44.19%	0.107
Differentiation	Moderate-poor	63	30	32.26%	0.311
Differentiation	Well	13	10	43.48%	0.311
DTAV (cm)	< 5	33	25	43.10%	0.11
DTAV (cm)	≥ 5	48	20	29.41%	0.11
TL (cm)	> 3	64	27	29.67%	0.008
TL (cm)	≤ 3	13	17	56.67%	0.008
TCE	< 50%	8	4	33.33%	0.944
TCE	≥ 50%	65	34	34.34%	0.944
cT	2	0	2	100.00%	0.061
	3	58	35	37.63%
	4	18	5	21.74%
cN	+	62	36	36.73%	0.946
cN	-	16	9	36.00%	0.946
MRF	-	49	39	44.32%	0.002
MRF	+	32	6	15.79%	0.002

Platelet, apolipoprotein A-1, apolipoprotein B, and the interval were calculated as metrological data, and others are counting data. pCR: Complete pathological response; NLR: Neutrophil-lymphocyte ratio; DTAV: Distance of tumor from the anal verge; TL: Tumor length; TCE: Tumor circumferential extent; PLT: Platelet; ApoA1: Apolipoprotein A-1; ApoB: Apolipoprotein B; MRF: Mesorectal fascia; CEA: Carcinoembryonic antigen.

Table 9 Predictive factors for complete pathological response in multivariate logistic regression analysis for the mFOLFOX6-RT regimen

Variable		P value	OR	95%CI
TL (cm)	≤ 3	0.046	2.452	1.015-5.926
TL (cm)	> 3		1
MRF	-	0.008	3.829	1.42-10.325
MRF	+		1

TL: Tumor length; MRF: Mesorectal fascia.

Table 10 Predictive factors for complete pathological response in univariate logistic regression analysis for the mFOLFOX6 regimen

Variable		Non-pCR (n = 148) n P₅₀ (P₂₅-P₇₅)	pCR (n = 14) n P₅₀ (P₂₅-P₇₅)	pCR rate	P-value
Gender	Male	99	8	7.48%	0.418
Gender	Female	47	6	11.32%	0.418
Age (yr)	≤ 60	92	10	9.80%	0.532
Age (yr)	> 60	54	4	6.90%	0.532
BMI (kg/cm²)	< 25	107	11	9.32%	0.477
BMI (kg/cm²)	≥ 25	34	2	5.56%	0.477
Hemoglobin (g/L)	≤ 125	53	2	3.64%	0.093
Hemoglobin (g/L)	> 125	75	10	11.76%	0.093
NLR	> 3	16	1	5.88%	0.673
NLR	≤ 3	112	11	8.94%	0.673
PLT (×10⁹/L)		127.5 (117.5-139)	137.5 (127-142.25)		0.82
ApoA1 (g/L)		1.28 (1.11-1.42)	1.3 (1.15-1.46)		0.542
ApoB (g/L)		0.96 (0.77-1.13)	1.13 (0.86-1.3)		0.051
The interval		21.5 (18-25)	25 (19.25-26.75)		0.09
CEA (ng/mL)	> 5	72	7	8.86%	0.889
CEA (ng/mL)	≤ 5	56	5	8.20%	0.889
Differentiation	Moderate-poor	129	6	4.44%	0
Differentiation	Well	14	6	30.00%	0
DTAV (cm)	< 5	55	7	11.29%	0.345
DTAV (cm)	≥ 5	93	7	7.00%	0.345
TL (cm)	> 3	99	6	5.71%	0.02
TL (cm)	≤ 3	37	8	17.78%	0.02
TCE	< 50%	19	3	13.64%	0.413
TCE	≥ 50%	112	10	8.20%	0.413
cT	2	9	1	10.00%	0.974
	3	101	11	9.82%
	4	22	2	8.33%
cN	+	100	10	9.09%	0.866
cN	-	36	4	10.00%	0.866
MRF	-	108	11	9.24%	0.707
MRF	+	38	3	7.32%	0.707

Platelet, apolipoprotein A-1, apolipoprotein B, and the interval were calculated as metrological data, and others are counting data. pCR: Complete pathological response; NLR: Neutrophil-lymphocyte ratio; DTAV: Distance of tumor from the anal verge; TL: Tumor length; TCE: Tumor circumferential extent; PLT: Platelet; ApoA1: Apolipoprotein A-1; ApoB: Apolipoprotein B; MRF: Mesorectal fascia; CEA: Carcinoembryonic antigen.

Table 11 Predictive factors for complete pathological response in multivariate logistic regression analysis for the mFOLFOX6 regimen

Variable		P-value	OR	95%CI
Differentiation	Well	0.002	8.881	2.263-34.85
Differentiation	Moderate-poor		1
TL	≤ 3	0.022	4.805	1.25-18.466
TL	> 3		1

TL: Tumor length.

Citation: Ren DL, Li J, Yu HC, Peng SY, Lin WD, Wang XL, Ghoorun RA, Luo YX. Nomograms for predicting pathological response to neoadjuvant treatments in patients with rectal cancer. World J Gastroenterol 2019; 25(1): 118-137
URL: https://www.wjgnet.com/1007-9327/full/v25/i1/118.htm
DOI: https://dx.doi.org/10.3748/wjg.v25.i1.118