Establishment of a prediction model for severe acute radiation enteritis associated with cervical cancer radiotherapy

Table 1 Baseline characteristics of all patients (n = 50)

Characteristic	n (%)
Age, median (IQR)	51.0 (45.5-62.0)
Weight, IQR	55.0 (50.5-61.8)
BMI/kg/m2, IQR	21.5 (20.7-22.9)
aCCI
2-3/4-5	38 (76)/12 (24)
Pathological diagnosis
Squamous cell carcinoma	47 (94)
Adenocarcinoma	1 (2)
Adenosquamous carcinoma	2 (4)
T
> 4 cm/≤ 4 cm	24 (48)/26 (52)
N
Negative/positive	15 (30)/35 (70)
Metastatic pelvic lymph nodes
Positive/negative	14 (28)/36 (72)
Metastatic common iliac lymph nodes
Positive/negative	5 (10)/45 (90)
Para-aortic lymph nodes
Positive/negative	2 (4)/48 (96)
FIGO staging
I/II/III/IVA	19 (38)/21 (42)/5 (10)/5 (10)
LVSI
Positive/negative	16 (32)/34 (68)
Degree of differentiation
Low and medium differentiation/high differentiation	40 (80)/10 (20)
Degree of infiltration
Shallow 1/3/Medium 1/3/Deep 1/3	10 (20)/16 (32)/24 (48)
Incised margin
R1 + R2/R0	5 (10)/45 (90)
Danger degree
Low/medium/high risk	15 (30)/12 (24)/23 (46)
HPV
Positive/negative	46 (92)/4 (8)
SCC
Abnormally elevated/no abnormality observed	17 (34)/33 (66)
RE
Occurred/not occurred	42 (84)/8 (16)
SARE/Non-SARE	15 (30)/35 (70)
Operation
Radical surgery/no surgery	36 (72)/14 (28)
Chemotherapy
CCRT/SCRT	18 (36)/32 (64)
Pelvic External Radiation Dose, IQR	45.0 (45.0-48.0)
Para-aortic extension field
Radiotherapy/no radiotherapy	4 (8)/46 (92)

aCCI: Adjusted Charlson Comorbidity Index; SARE: Severe acute radiation enteritis; CCRT: Concurrent chemoradiotherapy; SCRT: Sequential chemoradiotherapy; SCC: Squamous cell carcinoma; HPV: Human papillomavirus.

Table 2 Comparison of general data between postoperative adjuvant radiotherapy and radical radiotherapy for patients with cervical cancer, n (%)

Factor	Postoperative adjuvant radiotherapy group	Radical radiotherapy group	T/χ2 values	P value
Age/yr	48.25 ± 8.05	61.86 ± 13.17	-4.450	< 0.001
Young and middle-aged	33 (92)	5 (36)	17.301	< 0.001
Old age	3 (8)	9 (64)
Weight	57.31 ± 8.00	53.07 ± 8.74	1.638	0.108
BMI/kg/m2	21.86 ± 2.07	20.21 ± 2.79	2.284	0.027
Tumor type				0.1861
Squamous cell carcinoma	35 (97)	12 (86)
Adenocarcinoma	0 (0)	1 (7)
Adenosquamous carcinoma	1 (3)	1 (7)
CCRT			0.397	0.529
Implement	12 (33)	6 (43)
Not implemented	24 (67)	8 (57)
Para-aortic extended field radiotherapy				0.1861
Implement	1 (3)	2 (14)
Not implemented	35 (97)	12 (86)
RE			-	1.0001
Occurred	30 (83)	12 (86)
Did not occur	6 (17)	2 (14)
SARE			2.286	0.131
Occurred	13 (36)	2 (14)
Did not occur	23 (64)	12 (86)

¹Fisher exact probability method.

Data are shown as n (%) or mean ± SD. SARE: Severe acute radiation enteritis; CCRT: Concurrent chemoradiotherapy.

Table 3 Organs at risk dose-volume comparison between adjuvant radiotherapy (n = 36) and radical radiotherapy (n = 14) after cervical cancer surgery (%)

OAR	Group	V20	V25	V30	V35	V40
Small intestine	Postoperative adjuvant radiotherapy group	77.41 ± 16.49	51.90 ± 10.99	39.51 ± 8.24	26.40 ± 5.50	19.25 ± 4.12
	Radical radiotherapy group	67.75 ± 14.10	50.11 ± 9.86	32.92 ± 7.91	25.18 ± 7.12	15.07 ± 4.65
	Z value	-2.377	-0.864	-2.701	-0.367	-3.003
	P value	0.017	0.387	0.007	0.713	0.003
Colon	Postoperative adjuvant radiotherapy group	100.00 ± 0.00	99.88 ± 0.73	98.26 ± 6.09	91.36 ± 11.67	75.64 ± 12.59
	Radical radiotherapy group	95.57 ± 16.59	95.34 ± 17.44	94.21 ± 21.66	91.09 ± 21.12	84.17 ± 7.94
	Z value	-1.604	-0.732	-0.332	-0.750	-2.247
	P value	0.109	0.464	0.740	0.453	0.025
Rectum	Postoperative adjuvant radiotherapy group	100.00 ± 0.00	100.00 ± 0.00	99.17 ± 2.90	95.63 ± 9.41	75.64 ± 12.59
	Radical radiotherapy group	100.00 ± 0.00	100.00 ± 0.00	100.00 ± 0.00	99.60 ± 1.48	84.17 ± 7.94
	Z value	0.000	0.000	-1.102	-1.745	-2.247
	P value	1.000	1.000	0.270	0.081	0.025
Bladder	Postoperative adjuvant radiotherapy group	70.87 ± 28.16	68.75 ± 24.41	47.18 ± 23.63	35.58 ± 16.04	27.33 ± 12.22
	Radical radiotherapy group	74.08 ± 27.93	71.94 ± 25.87	52.54 ± 28.93	40.40 ± 21.04	31.18 ± 16.28
	T-value	-0.354	-0.523	-0.519	-0.605	-0.627
	P value	0.723	0.601	0.604	0.545	0.531
Femoral head	Postoperative adjuvant radiotherapy group	48.55 ± 28.80	34.45 ± 22.27	24.73 ± 16.00	18.12 ± 11.68	12.23 ± 8.10
	Radical radiotherapy group	39.60 ± 19.76	27.13 ± 14.03	19.54 ± 10.07	14.42 ± 7.69	9.47 ± 5.37
	T-value	-0.951	-0.929	-0.994	-0.929	-0.983
	P value	0.342	0.353	0.320	0.353	0.326

OAR: Organs at risk.

Table 4 Comparison of the incidence of acute radiation enteritis in patients with cervical cancer treated with adjuvant radiotherapy (n = 36) and radical radiotherapy (n = 14), n (%)

Adverse reaction	Group	Level 0	Level 1	Level 2	Level 3	χ2 value	P value
Diarrhea	Postoperative adjuvant radiotherapy group	10 (28)	19 (53)	5 (14)	2 (5)	2.748	0.432
	Radical radiotherapy group	3 (21)	10 (72)	0 (0)	1 (7)
Abdominal pain	Postoperative adjuvant radiotherapy group	21 (58)	12 (33)	3 (9)	0 (0)	1.423	0.491
	Radical radiotherapy group	8 (57)	6 (43)	0 (0)	0 (0)
Colitis	Postoperative adjuvant radiotherapy group	25 (69)	11 (31)	0 (0)	0 (0)	-	0.1401
	Radical radiotherapy group	13 (93)	1 (7)	0 (0)	0 (0)
Anal bulging	Postoperative adjuvant radiotherapy group	22 (61)	9 (25)	5 (14)	0 (0)	1.374	0.503
	Radical radiotherapy group	11 (79)	2 (14)	1 (7)	0 (0)
Blood in the stool	Postoperative adjuvant radiotherapy group	23 (64)	13 (36)	0 (0)	0 (0)		0.1791
	Radical radiotherapy group	12 (86)	2 (14)	0 (0)	0 (0)
Myelosuppression	Postoperative adjuvant radiotherapy group	12 (33)	9 (25)	10 (28)	5 (14)	3.691	0.297
	Radical radiotherapy group	3 (21)	4 (29)	2 (14)	5 (36)

¹Fisher exact probability method.

Table 5 Comparison of general data between patients with cervical cancer with severe acute radiation enteritis or no severe acute radiation enteritis

Factor	SARE (n = X)	No SARE (n = X)	OR (95%CI)	P value
	Median (IQR)	Median (IQR)
Clinical factors
Elderly (> 60 yr)/young and middle-aged (20-60 yr)			0.123 (0.015-1.040)	0.054
Age	47.5 (37.0-54.0)	53.0 (46.0-63.0)	0.930 (0.872-0.992)	0.027
Weight	53.0 (51.0-60.9)	56.0 (50.0-61.8)	0.983 (0.918-1.054)	0.631
BMI/kg/m2	20.5 (19.7-22.2)	21.9 (20.4-23.0)	0.936 (0.746-1.174)	0.566
ACCI (2-3/4-5)			0.123 (0.015-1.040)	0.054
Tumor type (squamous/non-squamous)			0.848 (0.139-5.179)	0.859
T (> 4 cm/≤ 4 cm)			0.510 (0.153-1.695)	0.272
N (positive/negative)			0.615 (0.165-2.298)	0.538
Metastatic pelvic lymph nodes (positive/negative)			0.694 (0.185-2.611)	0.589
Common iliac lymph node metastasis (positive/negative)			0.427 (0.046-3.980)	0.455
Para-aortic lymph nodes (positive/negative)			1.471 (1.216-1.779)	0.999
FIGO stage (IIB-IVA/IB-IIA)			1.108 (0.328-3.739)	0.869
LVSI (positive/negative)			0.548 (0.147-2.034)	0.368
Differentiation degree (low and medium differentiation/high differentiation)			1.011 (0.225-4.536)	0.988
Infiltration degree (shallow 1/3/medium depth 1/3)			0.837 (0.191-3.673)	0.813
Incisal margin (R1 + R2/R0)			0.427 (0.046-3.980)	0.455
Risk (low risk/medium high risk)			1.227 (0.340-4.242)	0.754
HPV (positive/negative)			1.324 (0.127-13.785)	0.815
SCC (abnormally elevated/not abnormal)			0.303 (0.074-1.245)	0.098
Surgery (performed/not performed)			2.080 (0.497-8.706)	0.316
CCRT (implemented/not implemented)			6.042 (1.681-21.718)	0.006
Myelosuppression (Grade 1-3/Grade 0)			0.617 (0.178-2.144)	0.446
Diarrhea (Grade 1-3/Grade 0)			NA	0.999
Abdominal pain (Grade 1-3/Grade 0)			25.375 (4.750-135.559)	< 0.001
Colitis (Grade 1-3/Grade 0)			38.500 (6.530-226.993)	< 0.001
Anal bulge (Grade 1-3/Grade 0)			5.185 (1.470-18.286)	0.010
Hematochezia (Grade 1-3/Grade 0)			NA	< 0.001
DAI score	2.8 (2.3-3.0)	1.7 (1.2-2.0)	152.546 (6.045-3849.771)	0.002
Physical dose parameters
Small intestine
V20 (%)	80.9 (68.6-93.7)	78.0 (66.8-82.5)	1.015 (0.975-1.056)	0.475
V25 (%)	58.2 (46.0-62.9)	52.0 (48.0-57.3)	1.014 (0.955-1.076)	0.659
V30 (%)	41.0 (35.1-47.6)	39.6 (31.1-42.1)	1.039 (0.961-1.122)	0.335
V35 (%)	29.6 (23.5-32.2)	26.9 (24.4-29.1)	1.032 (0.927-1.149)	0.569
V40 (%)	19.5 (16.8-23.3)	19.3 (13.3-20.7)	1.068 (0.928-1.229)	0.358
Rectum
V20 (%)	80.9 (68.6-93.7)	78.0 (66.8-82.5)	1.015 (0.975-1.056)	0.475
V25 (%)	58.2 (46.0-62.9)	52.0 (48.0-57.3)	1.014 (0.955-1.076)	0.659
V30 (%)	41.0 (35.1-47.6)	39.6 (31.1-42.1)	1.039 (0.961-1.122)	0.335
V35 (%)	29.6 (23.5-32.2)	26.9 (24.4-29.1)	1.032 (0.927-1.149)	0.569
V40 (%)	19.5 (16.8-23.3)	19.3 (13.3-20.7)	1.068 (0.928-1.229)	0.358
Colon
V20 (%)	100.0 (100.0-100.0)	100.0 (100.0-100.0)	NA	NA
V25 (%)	100.0 (100.0-100.0)	100.0 (100.0-100.0)	NA	NA
V30 (%)	100.0 (100.0-100.0)	100.0 (100.0-100.0)	0.982 (0.775-1.246)	0.883
V35 (%)	100.0 (99.1-100.0)	100.0 (100.0-100.0)	0.981 (0.915-1.052)	0.981
V40 (%)	80.4 (71.3-89.2)	79.3 (72.1-87.8)	1.005 (0.956-1.056)	0.851
Femoral head
V20 (%)	35.4 (19.7-57.3)	48.6 (22.9-65.2)	0.994 (0.971-1.017)	0.586
V25 (%)	24.8 (13.7-40.1)	31.6 (16.0-45.1)	0.996 (0.967-1.026)	0.797
V30 (%)	17.7 (9.8-29.6)	22.6 (11.4-32.6)	0.997 (0.957-1.039)	0.877
V35 (%)	13.3 (7.4-20.0)	16.9 (8.6-24.5)	0.989 (0.935-1.047)	0.711
V40 (%)	8.9 (4.9-14.3)	11.3 (5.7-16.3)	0.993 (0.916-1.076)	0.858
Total pelvic lymphatic drainage dose (Gy)	45.0 (45.0-45.0)	45.0 (45.0-48.5)	1.194 (0.877-1.625)	0.261
Para-aortic extended field radiotherapy (performed/not performed)			1.485 (1.222-1.804)	0.999

ACCI: Adjusted Charlson Comorbidity Index; CCRT: Concurrent chemoradiotherapy; SCC: Squamous cell carcinoma; HPV: Human papillomavirus; NA: Not available; DAI: Disease activity index.

Table 6 Multivariate analysis of influencing factors of severe radiation enteritis in 50 patients with cervical cancer treated with radiotherapy

	B	SE	Exp (B)	95%CI		Wald χ2	P value
				Lower	Upper
DAI score	4.106	1.371	60.705	4.134	891.506	9.463	0.003
Anal bulge rating	2.925	1.229	18.636	1.677	207.114	7.664	0.017

DAI: Disease activity index; 95%CI: 95% confidence interval.