Lymphocyte-to-monocyte ratio before chemoradiotherapy represents a prognostic predictor for locally advanced rectal cancer

Figures & data

Figure 1 ROC for determination of the cutoff value for the LMR in patients with locally advanced rectal cancer with preoperative chemoradiotherapy.

Abbreviations: ROC, receiver operating curve; LMR, lymphocyte-to-monocyte ratio; AUC, area under the curve.

Table 1 Clinical characteristics of the patients stratified by LMR

Characteristics	Total n=317 (%)	LMR
		≤4.91	>4.91	P-value
Age (years)				0.538
≤60	212 (66.9)	138	74
>60	105 (33.1)	72	33
Sex				0.022
Male	205 (64.7)	145	60
Female	112 (35.3)	65	47
Cycles of neoadjuvant XELOX regimen				<0.002
1	13 (4.1)	10	3
2	162 (51.1)	117	45
3	63 (19.9)	42	21
4	79 (24.9)	41	38
Radiotherapy model				<0.002
IMRT	154 (48.6)	87	67
3D-CRT	146 (46.1)	110	36
Conventional RT	17 (5.4)	13	4
Radiation dose (Gy)				0.001
46	171 (53.9)	127	44
50	146 (46.1)	83	63
Interval from radiotherapy to surgery (days)				0.174
≤49	210 (66.2)	117	93
>49	107 (33.8)	51	56
Tumor size (cm)				0.133
≤3	226 (71.3)	144	82
>3	91 (28.7)	66	25
DAV (cm)				0.176
≤5	165 (52.1)	115	50
>5	152 (47.9)	95	57
Postoperative TNM stage				<0.191
pCR	85 (26.8)	53	32
I	62 (19.6)	40	22
IIA	59 (18.6)	35	24
IIB	42 (13.2)	35	7
IIIA	16 (5.0)	7	9
IIIB	48 (15.1)	36	12
IIIC	5 (2.0)	3	2
TRG				0.097
1–2	160 (50.5)	99	61
3–5	157 (49.5)	111	46
Surgical type				<0.064
Anterior resection	203 (64.0)	125	78
Abdominal perineal resection	106 (33.4)	79	27
Others	8 (2.5)	6	2
Tumor differentiation				0.841
Well differentiated	34 (10.7)	22	12
Moderately or poorly differentiated	283 (89.3)	188	95
Pre-CRT CEA (ng/mL)				0.528
≤5	161 (50.8)	104	57
>5	156 (49.2)	106	50
Pre-CRT CA199 (U/mL)				0.120
≤35	264 (83.3)	170	94
>35	53 (16.7)	40	13

Note: P-value, the correlation between clinical–pathological parameters and LMR was assessed by the chi-square test or Fisher’s exact test.

Abbreviations: LMR, lymphocyte-to-monocyte ratio; XELOX, oxaliplatin 130 mg/m² administered intravenously on Day 1 and capecitabine administered orally 1,000 mg/m² twice daily on Days 1–14 for a 3-week cycle; IMRT, intensity-modulated radiation therapy; 3D-CRT, 3-dimensional conformal radiation therapy; RT, radiotherapy; DAV, distance of inferior tumor margin from the anal verge; TNM, tumor node metastasis; pCR, pathologic complete response; TRG, tumor regression grade; CRT, chemoradiotherapy; CEA, carcinoembryonic antigen; CA199, cancer antigen 199.

Table 2 The univariate and multivariate analyses of the factors influencing tumor pathologic regression response in locally advanced rectal cancer after preoperative chemoradiotherapy

	Univariate analysis		Multivariate analysis
	OR (95% CI)	P-value	OR (95% CI)	P-value
Age (years)
≤60	1 (reference)		–
>60	0.941 (0.556–1.591)	0.820	–
Sex
Male	1 (reference)		–
Female	0.934 (0.557–1.568)	0.797	–
Cycles of preoperative XELOX regimen
1–2	1 (reference)		–
3–4	0.883 (0.536–1.453)	0.624	–
Radiotherapy model
IMRT	1 (reference)		–
3D-CRT	1.504 (0.896–2.524)	0.122	–
Conventional RT	1.054 (0.352–3.161)	0.925	–
Radiation dose (Gy)
46	1 (reference)		–
50	0.685 (0.416–1.129)	0.138	–
Interval from radiotherapy to surgery (days)
≤49	1 (reference)		–
>49	0.677 (0.411–1.115)	0.125	–
Tumor size (cm)
≤3	1 (reference)		–
>3	2.060 (1.120–3.789)	0.020	–
DAV (cm)
≤5	1 (reference)		–
>5	1.050 (0.638–1.727)	0.848	–
Clinical TNM stage
I/II	1 (reference)		–
III	1.420 (0.832–2.423)	0.199	–
Surgical type
Anterior resection	1 (reference)	0.289	–
Abdominal perineal resection	1.434 (0.831–2.474)		–
Others	2.937 (0.354–24.393)		–
Tumor differentiation
Well differentiated	1 (reference)		1 (reference)
Moderately or poorly differentiated	7.453 (3.445–16.125)	<0.001	7.453 (1.911–17.662)	0.002
Pre-CRT CEA (ng/mL)
≤5	1 (reference)		–
>5	3.113 (1.825–5.309)	<0.001	–
Pre-CRT CA199 (U/mL)
≤35	1 (reference)		–
>35	1.487 (0.727–3.043)	0.277	–
LMR
≤4.91	1 (reference)		–
>4.91	0.791 (0.471–1.328)	0.375	–

Notes: P-value; in logistic regression analysis, variables found to be statistically significant (P<0.05) in univariate analysis were entered into a logistic regression multivariate model using a forward conditional method. ‘–’ indicates multivariate analysis not performed.

Abbreviations: OR, odds ratio; CI, confidence interval; XELOX, oxaliplatin 130 mg/m² administered intravenously on Day 1 and capecitabine administered orally 1,000 mg/m² twice daily on Days 1–14 for a 3-week cycle; IMRT, intensity-modulated radiation therapy; 3D-CRT, 3-dimensional conformal radiation therapy; RT, radiotherapy; DAV, distance of inferior tumor margin from the anal verge; TNM, tumor node metastasis; CRT, chemoradiotherapy; CEA, carcinoembryonic antigen; CA199, cancer antigen 199; LMR, lymphocyte-to-monocyte ratio.

Figure 2 (A) Kaplan–Meier curves of LMR for 3-year OS, (B) Kaplan–Meier curves of LMR for 3-year DFS.

Abbreviations: LMR, lymphocyte-to-monocyte ratio; OS, overall survival; DFS, disease-free survival.

Table 3 The univariate and multivariate analyses of the factors influencing OS and DFS by the Cox proportional hazard model

	OS				DFS
	Univariate analysis		Multivariate analysis		Univariate analysis		Multivariate analysis
	HR (95% CI)	P-value	HR (95% CI)	P-value	HR (95% CI)	P-value	HR (95% CI)	P-value
Age (years)
≤60	1 (reference)		–		1 (reference)		–
>60	1.167 (0.711–1.915)	0.541	–		0.868 (0.530–1.420)	0.572	–
Sex
Male	1 (reference)		–		1 (reference)		–
Female	0.874 (0.525–1.457)	0.606	–		1.095 (0.685–1.752)	0.704	–
Cycles of preoperative XELOX regimen
1–2	1 (reference)		–		1 (reference)		–
3–4	0.931 (0.566–1.559)	0.785	–		1.007 (0.628–1.615)	0.977	–
Radiotherapy model
IMRT	1 (reference)	0.500	–		1 (reference)	0.732	–
3D-CRT	1.101 (0.646–1.876)		–		1.005 (0.618–1.634)		–
Conventional RT	1.685 (0.705–4.026)		–		1.406 (0.582–3.395)		–
Radiotherapy dose (Gy)
46	1 (reference)		–		1 (reference)		–
50	0.922 (0.806–1.054)	0.231	–		0.787 (0.486–1.276)	0.331	–
Interval from radiotherapy to surgery (days)
≤49	1 (reference)		–		1 (reference)		–
>49	0.714 (0.432–1.180)	0.189	–		0.658 (0.409–1.058)	0.084	–
Tumor size (cm)
≤3	1 (reference)		–		1 (reference)		1 (reference)
>3	1.852 (1.138–3.013)	0.013	–		2.035 (1.284–3.225)	0.002	1.927 (1.214–3.059)	0.005
DAV (cm)
≤5	1 (reference)		–		1 (reference)		–
>5	0.705 (0.430–1.153)	0.163	–		1.067 (0.676–1.683)	0.782	–
Postoperative TNM stage
pCR I–II	1 (reference)		1 (reference)		1 (reference)		1 (reference)
III	3.253 (2.000–5.291)	<0.001	3.004 (1.837–4.912)	<0.001	3.300 (2.071–5.257)	<0.001	3.182 (1.996–5.075)	<0.001
TRG
1–2	1 (reference)		–		1 (reference)		–
3–5	2.062 (1.245–3.414)	0.005	–		1.926 (1.199–3.092)	0.007	–
Surgical type
Anterior resection	1 (reference)	0.017	–		1 (reference)	0.099	–
Abdominal perineal resection	1.702 (1.037–2.795)		–		1.347 (0.837–2.168)		–
Others	3.503 (1.240–9.897)		–		2.805 (1.004–7.834)		–
Tumor differentiation
Well differentiated	1 (reference)		–		1 (reference)		–
Moderately or poorly differentiated	2.754 (0.865–8.771)	0.087	–		2.393 (0.873–6.555)	0.090	–
Pre-CRT CEA (ng/mL)
≤5	1 (reference)		–		1 (reference)		–
>5	1.581 (0.973–2.570)	0.064			1.530 (0.965–2.424)	0.070	–
Pre-CRT CA199 (U/mL)
≤35	1 (reference)		1 (reference)		1 (reference)		–
>35	2.332 (1.381–3.940)	0.002	1.906 (1.116–3.254)	0.018	2.025 (1.212–3.384)	0.007	–
LMR
≤4.91	1 (reference)		1 (reference)		1 (reference)		–
>4.91	0.493 (0.269–0.904)	0.022	0.538 (0.292–0.991)	0.047	0.640 (0.376–1.089)	0.100	–

Notes: P-value; in Cox hazards regression analysis, variables found to be statistically significant (P<0.05) in univariate analysis were entered into a Cox regression multivariate model using a forward conditional method. ‘–’ indicates multivariate analysis not performed.

Abbreviations: OS, overall survival; DFS, disease-free survival; HR, hazard ratio, CI, confidence interval; XELOX, oxaliplatin 130 mg/m² administered intravenously on Day 1 and capecitabine administered orally 1,000 mg/m² twice daily on Days 1–14 for a 3-week cycle; IMRT, intensity-modulated radiation therapy; 3D-CRT, 3-dimensional conformal radiation therapy; RT, radiotherapy; DAV, distance of inferior tumor margin from the anal verge; TNM, tumor node metastasis; pCR, pathologic complete response; TRG, tumor regression grade; CRT, chemoradiotherapy; CEA, carcinoembryonic antigen; CA199, cancer antigen 199; LMR, lymphocyte-to-monocyte ratio.