Predictive value of indirect bilirubin before neoadjuvant chemoradiotherapy in evaluating prognosis of local advanced rectal cancer patients

doi:10.4251/wjgo.v14.i11.2224

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Nov 15, 2022 (publication date) through Apr 24, 2024

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World Journal of Gastrointestinal Oncology

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World J Gastrointest Oncol. Nov 15, 2022; 14(11): 2224-2237
Published online Nov 15, 2022. doi: 10.4251/wjgo.v14.i11.2224

Table 1 Clinical characteristics and treatment strategies of local advanced rectal cancer patients

Characteristic	Pre-IBIL ≤ 6.2 μmol/L (n = 163)	Pre-IBIL > 6.2 μmol/L (n = 161)	P value	All patients (n = 324)
Age, yr			0.305
< 60	88 (53.99)	97 (60.25)		185 (57.10)
≥ 60	75 (46.01)	64 (39.75)		139 (42.90)
Sex			0.007
Female	61 (37.42)	37 (22.98)		98 (30.25)
Male	102 (62.58)	124 (77.02)		226 (69.75)
BMI, kg/m²			0.317
< 18.5	7 (4.29)	4 (2.48)		11 (3.40)
18.5-23.9	86 (52.76)	73 (45.34)		159 (49.07)
24.0-27.9	52 (31.90)	66 (40.99)		118 (36.42)
≥ 28.0	18 (11.04)	18 (11.18)		36 (11.11)
Smoking history			0.581
No	87 (53.37)	80 (49.69)		167 (51.54)
Yes	76 (46.63)	81 (50.31)		157 (48.46)
Drinking history			0.925
No	96 (58.90)	93 (57.76)		189 (58.33)
Yes	67 (41.10)	68 (42.24)		135 (41.67)
Chronic disease history			0.624
No	100 (61.35)	104 (64.60)		204 (62.96)
Yes	63 (38.65)	57 (35.40)		120 (37.04)
cTNM stage			0.839
II	23 (14.11)	25 (15.53)		48 (14.81)
III	140 (85.89)	136 (84.47)		276 (85.19)
nCRT with surgery interval, d			0.573
31-60	88 (53.99)	79 (49.07)		167 (51.54)
61-90	63 (38.65)	66 (40.99)		129 (39.81)
> 90	12 (7.36)	16 (9.94)		28 (8.64)
Inferior margin			0.373
≤ 5 cm	109 (66.87)	116 (72.05)		225 (69.44)
> 5 cm	54 (33.13)	45 (27.95)		99 (30.56)
TRG			0.160
1	14 (8.59)	16 (9.94)		30 (9.26)
2	90 (55.21)	72 (44.72)		162 (50.00)
3	41 (25.15)	43 (26.71)		84 (25.93)
4	18 (11.04)	30 (18.63)		48 (14.81)
Vascular invasion			0.471
Negative	155 (95.09)	149 (92.55)		304 (93.83)
Positive	8 (4.91)	12 (7.45)		20 (6.17)
Neural invasion			0.846
Negative	130 (79.75)	126 (78.26)		256 (79.01)
Positive	33 (20.25)	35 (21.74)		68 (20.99)
Radiotherapy type before surgery			0.688
VMAT	146 (89.57)	140 (86.96)		286 (88.27)
IMRT	14 (8.59)	16 (9.94)		30 (9.26)
3D-CRT	3 (1.84)	5 (3.11)		8 (2.47)
Chemotherapy type before surgery			0.975
Capecitabine	145 (88.96)	144 (89.44)		289 (89.20)
Capecitabine + platinum	9 (5.52)	9 (5.59)		18 (5.56)
Other	9 (5.52)	8 (4.97)		17 (5.25)
Adjuvant chemotherapy			0.383
No	57 (34.97)	48 (29.81)		105 (32.41)
Yes	106 (65.03)	113 (70.19)		219 (67.59)
Pre-CEA			0.832
≤ 5 ng/mL	91 (55.83)	87 (54.04)		178 (54.94)
> 5 ng/mL	72 (44.17)	74 (45.96)		146 (45.06)
Pre-CA19-9			0.931
≤ 27 U/mL	131 (80.37)	131 (81.37)		262 (80.86)
> 27 U/mL	32 (19.63)	30 (18.63)		62 (19.14)

nCRT: Neoadjuvant chemoradiotherapy; pre-IBIL: Indirect bilirubin before neoadjuvant chemoradiotherapy; BMI: Body mass index; TRG: Tumor regression grade; VMAT: Volumetric modulated arc therapy; IMRT: Intensity modulated radiation therapy; 3D-CRT: 3-dimensional conformal radiation therapy; pre-CEA: Carcinoembryonic antigen before neoadjuvant chemoradiotherapy; pre-CA19-9: Carbohydrate antigen 19-9 before neoadjuvant chemoradiotherapy.

Table 2 Cox regression analysis of prognostic factors for overall survival

Characteristic	Univariable analysis		Multivariable analysis
Characteristic	HR (95%CI)	P value	HR (95%CI)	P value
Pre-IBIL
≤ 6.2 μmol/L	Reference		Reference
> 6.2 μmol/L	1.71 (1.01-2.87)	0.045	1.77 (1.04-3.01)	0.035
Age, yr
< 60	Reference
≥ 60	1.39 (0.84-2.31)	0.199
Sex
Female	Reference
Male	1.16 (0.66-2.04)	0.596
BMI, kg/m²
< 18.5	Reference
18.5-23.9	0.74 (0.23-2.43)	0.624
24.0-27.9	0.57 (0.17-1.93)	0.370
≥ 28.0	0.27 (0.05-1.32)	0.105
Smoking history
No	Reference		Reference
Yes	0.57 (0.34-0.97)	0.039	0.58 (0.34-1.00)	0.048
Drinking history
No	Reference
Yes	0.72 (0.42-1.23)	0.227
Chronic disease history
No	Reference
Yes	1.09 (0.65-1.82)	0.749
cTNM stage
II	Reference
III	2.54 (0.92-6.99)	0.072
nCRT with surgery interval, day
31-60	Reference
61-90	0.61 (0.35-1.07)	0.083
> 90	0.68 (0.24-1.92)	0.469
Inferior margin
≤ 5 cm	Reference
> 5 cm	0.91 (0.53-1.59)	0.752
TRG
1	Reference		Reference
2	0.35 (0.18-0.67)	0.002	0.37 (0.18-0.75)	0.006
3	0.23 (0.10-0.52)	< 0.001	0.27 (0.12-0.64)	0.003
4	0.17 (0.06-0.48)	< 0.001	0.18 (0.06-0.53)	0.002
Vascular invasion
Negative	Reference		Reference
Positive	3.79 (1.86-7.74)	< 0.001	2.93 (1.39-6.21)	0.005
Neural invasion
Negative	Reference		Reference
Positive	2.15 (1.26-3.69)	0.005	1.27 (0.69-2.31)	0.442
Radiotherapy type before surgery
VMAT	Reference
IMRT	1.68 (0.85-3.35)	0.137
3D-CRT	0.69 (0.09-4.98)	0.709
Chemotherapy type before surgery
Capecitabine	Reference
Capecitabine + platinum	1.45 (0.57-3.66)	0.431
Other	1.90 (0.76-4.78)	0.172
Adjuvant chemotherapy
No	Reference
Yes	0.60 (0.36-1.00)	0.050
Pre-CEA
≤ 5 ng/mL	Reference
> 5 ng/mL	1.44 (0.87-2.39)	0.158
Pre-CA19-9
≤ 27 U/mL	Reference		Reference
> 27 U/mL	2.05 (1.19-3.54)	0.010	2.05 (1.16-3.62)	0.014

HR: Hazard ratio; 95%CI: 95% confidence interval; nCRT: Neoadjuvant chemoradiotherapy; pre-IBIL: Indirect bilirubin before neoadjuvant chemoradiotherapy; BMI: Body mass index; TRG: Tumor regression grade; VMAT: Volumetric modulated arc therapy; IMRT: Intensity modulated radiation therapy; 3D-CRT: 3-dimensional conformal radiation therapy; pre-CEA: Carcinoembryonic antigen before neoadjuvant chemoradiotherapy; pre-CA19-9: Carbohydrate antigen 19-9 before neoadjuvant chemoradiotherapy.

Table 3 Cox regression analysis of prognostic factors for disease-free survival

Characteristic	Univariable analysis		Multivariable analysis
Characteristic	HR (95%CI)	P value	HR (95%CI)	P value
Pre-IBIL
≤ 6.2 μmol/L	Reference		Reference
> 6.2 μmol/L	1.68 (1.12-2.53)	0.013	1.86 (1.22-2.84)	0.004
Age, yr
< 60	Reference
≥ 60	1.16 (0.78-1.74)	0.456
Sex
Female	Reference
Male	0.84 (0.55-1.28)	0.414
BMI, kg/m²
< 18.5	Reference		Reference
18.5-23.9	0.64 (0.26-1.61)	0.346	0.46 (0.18-1.17)	0.102
24.0-27.9	0.62 (0.24-1.57)	0.312	0.50 (0.19-1.30)	0.157
≥ 28.0	0.25 (0.07-0.87)	0.029	0.19 (0.05-0.66)	0.009
Smoking history
No	Reference
Yes	0.72 (0.48-1.08)	0.108
Drinking history
No	Reference
Yes	0.71 (0.47-1.07)	0.103
Chronic disease history
No	Reference
Yes	1.07 (0.72-1.61)	0.732
cTNM stage
II	Reference
III	1.49 (0.80-2.80)	0.210
nCRT with surgery interval, d
31-60	Reference		Reference
61-90	0.64 (0.41-0.99)	0.047	0.63 (0.40-0.99)	0.044
> 90	0.84 (0.40-1.77)	0.655	0.63 (0.29-1.35)	0.235
Inferior margin
≤ 5 cm	Reference
> 5 cm	0.80 (0.51-1.25)	0.318
TRG
1	Reference		Reference
2	0.45 (0.26-0.79)	0.006	0.43 (0.24-0.78)	0.005
3	0.29 (0.15-0.57)	< 0.001	0.30 (0.15-0.62)	0.001
4	0.31 (0.15-0.66)	0.002	0.31 (0.14-0.70)	0.005
Vascular invasion
Negative	Reference		Reference
Positive	2.54 (1.32-4.90)	0.005	2.24 (1.13-4.44)	0.021
Neural invasion
Negative	Reference		Reference
Positive	1.82 (1.17-2.82)	0.008	1.34 (0.82-2.18)	0.238
Radiotherapy type before surgery
VMAT	Reference
IMRT	1.07 (0.57-2.01)	0.836
3D-CRT	0.83 (0.20-3.37)	0.791
Chemotherapy type before surgery
Capecitabine	Reference
Capecitabine + platinum	0.98 (0.43-2.26)	0.969
Other	1.56 (0.72-3.37)	0.262
Adjuvant chemotherapy
No	Reference
Yes	0.89 (0.59-1.35)	0.584
Pre-CEA
≤ 5 ng/mL	Reference
> 5 ng/mL	1.33 (0.89-1.98)	0.158
Pre-CA19-9
≤ 27 U/mL	Reference
> 27 U/mL	1.47 (0.92-2.33)	0.104

Citation: Li SF, Wei R, Yu GH, Jiang Z. Predictive value of indirect bilirubin before neoadjuvant chemoradiotherapy in evaluating prognosis of local advanced rectal cancer patients. World J Gastrointest Oncol 2022; 14(11): 2224-2237
URL: https://www.wjgnet.com/1948-5204/full/v14/i11/2224.htm
DOI: https://dx.doi.org/10.4251/wjgo.v14.i11.2224