Dose-response relationships of the sigmoid for urgency syndrome after gynecological radiotherapy

Figures & data

Table 1. Factor loadings for the symptoms associated with ‘radiation-induced urgency syndrome’^a.

Symptoms	Factor loadings
Loose stools	0.714
Leakage of loose stools while awake	0.400
Leakage of loose stools while asleep	0.220
Involuntary unspecified flatulence	0.247
Involuntary foul-smelling flatulence	0.273
Abdominal bloating	0.324
Need to repeat defecation within 1 h	0.606
Sudden defecation urgency requiring lavatory	0.850
Degree of capacity to hold stools during urgency	0.693
Immediate need to defecate	0.738
Fecal leakage without forewarning despite pre-emptied bowel	0.351
Defecation into clothing without forewarning	0.261
Anal itching	0.230
Anal pain	0.221
Abdominal pain	0.344

^a Information are in detail presented in our previous study [1].

Figure 1. Organs at risk in lateral view: dark green: anal-sphincter; light green: rectum; orange: sigmoid; yellow: small intestines.

Table 2. Demographic, clinical characteristics and treatment characteristics of survivors with or without ‘radiation-induced urgency syndrome’ after pelvic radiation therapy.

	Survivors with the symptom,N = 24	Survivors without the symptom,N = 74	p value
Age (SD)
Mean age, years	62.4 (10)	62.1 (10)	.97
Smoking, n/N (%)			.39
Current smoker	7/24 (29)	24/72 (33)
Former smoker	13/24 (54)	28/72 (39)
Never smoker	4/24 (17)	20/72 (28)
Delivery with birth weight >4 kg, n/N (%)			.37
0	8/24 (75)	61/72 (85)
1	5/24 (21)	9/72 (21)
≥2	4/24 (4)	20/72 (3)
Pelvic floor injury, n/N (%)
Perineum injury	0/24 (0)	8/73 (11)	.19
Anal sphincter injury	0/24 (0)	4/74 (5)	.57
Co-morbidities, n/N (%)
Rheumatism	3/24 (12)	7/73 (10)	.71
Diabetes mellitus	1/24 (4)	8/74 (11)	.45
Hypertension	7/24 (29)	22/73 (30)	1.00
Hemorrhoids, treatment for	1/24 (4)	5/74 (7)	1.00
Lactose intolerance	1/24 (4)	3/74 (4)	1.00
Diagnoses, n/N (%)			.66
Endometrial cancer	2/24 (8)	7/74 (9)
Cervical cancer	3/24 (12)	14/74 (19)
Ovarian cancer	10/24 (42)	23/74 (31)
Vulvar cancer	3/24 (12)	3/74 (4)
Vaginal cancer	0/24 (0)	3/74 (4)
Sarcoma	3/24 (12)	15/74 (20)
Fallopian tube cancer	3/24 (12)	9/74 (12)
Treatment characteristics
Treatment modalities, n/N (%)			.43
EBRT + surgery	12/24 (50)	30/74 (41)
EBRT + surgery + chemotherapy	12/24 (50)	35/74 (47)
EBRT + chemotherapy	0/24 (0)	7/74 (9)
EBRT only	0/24 (0)	2/74 (3)
EBRT doses (SD)
Total mean dose Gy	46 (11)	42.6 (6)	.20
Field technique, n/N (%)			.52
Two opposing fields	14/24 (58)	33/74 (45)
Four-field box	9/24 (38)	30/74 (41)
Target area, n/N (%)			.10
Pelvic field	6/24 (25)	36/74 (49)
Lower abdominal field	15/24 (62)	31/74 (42)
Abdominal field	0/24 (0)	3/74 (4)
Pelvic field + paraaortic lymph nodes	1/24 (4)	2/74 (3)
Pelvic or vulvar field + inguinal lymph nodes	2/74 (8)	2/74 (3)
Mean follow up time, months (SD)	7.7 (3)	7.9 (3)	.73

p value from t-test of mean values; SD: ±1 standard deviation; EBRT: external beam radiation therapy.

Table 3. Mean and maximum absorbed doses for the three OARs, for patients with and without ‘radiation-induced urgency syndrome’ and correlation coefficients between mean and maximum absorbed doses.

	Mean dose (SD)
Survivors with or without ‘radiation-induced urgency syndrome’	Rectum	Sigmoid colon	Small intestine
With	42.2 (7.3)	42.1 (6.1)	43.6 (6.2)
Without	37.0 (7.8)	37.8 (7.9)	40.8 (7.4)
AUC	0.66	0.67	0.60
p*	.005	.013	.106
	Maximum dose (SD)
With	44.7 (7.4)	44.7 (7.4)	49.0 (9.2)
Without	39.6 (8.5)	42.4 (8.6)	44.7 (9.8)
AUC	0.66	0.65	0.62
p	.009	.019	.062
	Relationship of mean and maximum dose
Pearson correlation coefficient r	0.97	0.81	0.80

^* p values from t-test of mean values. T-test performed at 5% significance level.

Figure 2. Dose–response curves of mean dose to the rectum, sigmoid colon and the small intestine using the (a) Probit model, (b) the Relative Seriality (RS) model, (c) the LKB model and (d) the mean dose to the sigmoid colon for Probit, the Relative Seriality (RS) and the LKB models. The black x show the survivors with the syndrome, while the gray x show the survivors without the syndrome.

Table 4. The maximum likelihood estimates of the dose–response parameters for ‘radiation-induced urgency syndrome’ for the three OARs using Probit, RS, LKB and EUD models and the values for the AUC.

	Rectum	Sigmoid	Small intestine
Probit
LL	−50.2	−51.0	−51.4
D50 (CI)	51.3 (48.3–54.6)	51.6 (48.7–54.9)	61.4 (56.4–67.5)
γ50 (CI)	1.19 (0.98–1.42)	1.20 (0.98–1.44)	0.90 (0.73–1.08)
a/b (CI)	0.59 (0.034–1.56)	2.02 (0.85–4.73)	10.3 (2.1–10^6)
AIC	106.4	108.0	108.8
Relative Seriality
LL	−50.3	−50.7	−51.4
D50 (CI)	51.4 (48.5–54.8)	51.6 (48.8–54.8)	61.5 (56.4–67.7)
γ50 (CI)	1.19 (9.8 × 10^−1–1.42)	1.25 (1.00–1.50)	0.89 (0.72–1.07)
s (CI)	7.0 × 10^−9 (10^−100–31.7)	2.8 (6.9 × 10^−8–100.0)	1.56 × 10^−7 (10^−100–14.9)
a/b (CI)	0.62 (0.62–0.62)	1.10 (1.10–1.10)	8.92 (8.919–8.927)
AIC	108.6	109.4	110.8
LKB
LL	−50.3	−50.6	−51.4
D50 (CI)	51.3 (48.4–54.6)	51.5 (48.8–54.6)	61.8 (56.7–67.9)
γ50 (CI)	1.19 (0.97–1.42)	1.27 (1.03–1.51)	0.92 (0.73–1.08)
M (CI)	0.47 (0.40–0.58)	0.44 (0.37–0.55)	0.61 (0.37–0.62)
n (CI)	9 × 10^6 (10^−40–10^40)	0.079 (0.017–0.44)	1.04 × 10^8
a/b (CI)	0.63 (0.40–0.86)	1.18 (0.32–2.04)	17.70 (17.70–17.70)
AIC	108.6	109.2	110.8
gEUD
a (1/n)	1.03 × 10^−7 (10^−40–10^+40)	12.7 (2.3–58.2)	9.6 × 10^−9 (10^−20–10^−20)
AUC (CI)	0.630	0.661	0.602

LL: Log likelihood value; CI: confidence intervals; AIC: Akaike information criterion; AUC: area under the ROC curve; D₅₀: dose giving 50% of complication probability (Gy); γ₅₀: normalized maximum gradient of the dose–response curve; s: Relative Seriality parameter; m: steepness of the dose–response curve; n: volume parameter; a: volume parameter.

Steineck G, Skokic V, Sjöberg F, et al. Identifying radiation-induced survivorship syndromes affecting bowel health in a cohort of gynecological cancer survivors. PLoS One. 2017;12:e0171461.

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