Radiotherapy-induced vaginal fibrosis in cervical cancer survivors

Figures & data

Table 1. Demographics and clinical characteristics of cervical cancer survivors and controls.

	Cervical cancer survivors (n = 34)	Controls (n = 37)
Age at time of study, mean (range)	41 (29–51)	40 (30–49)
Age – no. (%)
<30	2 (6)	–
30–34	3 (9)	6 (16)
35–39	8 (24)	8 (22)
40–44	11 (32)	15 (40)
45–50	9 (26)	8 (22)
>50	1 (3)	–
FIGO tumor stage – no. (%)
IB1	16 (47)	–
IB2	4 (12)	–
IIA	6 (17)	–
IIB	5 (15)	–
IIIB	3 (9)	–
Histology – no. (%)
Squamous cell carcinoma	25 (73)
Adenocarcinoma	4 (12)
Adenosquamous carcinoma	1 (3)
Clear cell carcinoma	4 (12)
Treatment – no. (%)
Preop brachytherapy + surgery	5 (15)
Preop brachytherapy + surgery + EBRT + chemo	8 (23)
Preop brachytherapy + surgery + EBRT	5 (15)
Surgery + EBRT + chemo (+ brachytherapy)	6 (18)
Surgery + EBRT (+ brachytherapy)	1 (3)
Primary CRT (+ brachytherapy)	9 (26)
Local hormonal therapy – no. (%)	13 (38)	–
Systemic hormonal therapy – no. (%)	27 (79)	–
Estrogen	23 (67)	–
Combined	4 (12)	–
Systemic and local hormonal therapy – no. (%)	9 (26)	–
Vaginal dilator – no. (%)	19 (56)	–

Chemo: concomitant chemotherapy; CRT: chemoradiotherapy; EBRT: external beam radiotherapy.

Table 2. Radiotherapy dose at the vaginal biopsy site in the cervical cancer survivors.

	Treatment Group I (n = 5)	Treatment Group IIA (n = 20)	Treatment Group IIB (n = 9)
Variable	Preop BT + surgery	Preop BT + surgery + post-HDR + EBRT	Primary radiochemotherapy	p Value^a
Dose of brachytherapy, median (range) (Gy)	0.0 (0–9.0)	0.0 (0–5.2)	1.9 (0–5.8)	0.962
Dose of EBRT, median (range) (Gy)	0.0 (0)	42.6 (33.9–49.3)^b	50.0 (46.0–48.0)^b	<0.001
Total dose, median (range) (Gy)	0.0 (0–9.0)	44.3 (38.8–49.3)^b	53.4 (47.9–69.0)^b	<0.001

^a p Values according to Kruskal-Wallis test

^b p < 0.001 comparing Group IIA and Group IIB according to Mann-Whitney U-test.

BT: Brachytherapy; EBRT: external beam radiotherapy.

Table 3. Vaginal characteristics among all cervical cancer survivors and controls, and cancer survivors divided in two different treatment groups.

					Treatment Group
	All cervical cancer survivors (n = 34)	Controls (n = 37)	p Value^a	Treatment Group I (n = 5)Preop BT + surgery	IIA + IIB (n = 29)EBRT + BT +/− surgery +/− chemo	p Value^a
Total dose at the biopsy site, median (range) (Gy)	44.3 (0–69.0)	0 (0)	–	0.0 (0–9.0)	44.8 (38.8–69)	<0.001
Length of vagina (cm), median (min–max)	7. 0 (5.0–9.0)	10.0 (7.0–13.0)	<0.001	7.5 (7.0–8.5)	7.0 (5.0–9.0)	0.044
Vaginal atrophy – no. (%)	31 (91)	0 (0)	–	3 (60)	28 (97)	0.046
Pelvic fibrosis – no. (%)	33 (97)	0 (0)	–	5 (100)	28 (97)	0.044
No signs	1 (3)	37 (100)	–	0 (0)	1 (3)	–
Mild	16 (47)	–	–	5 (100)	11 (38)	–
Moderate	14 (41)	–	–	0 (0)	14 (48)	–
Severe	3 (9)	–	–	0 (0)	3 (10)	–
Elastin, median % (range)	10.0 (0.8–18.1)	3.4 (0.9–11.6)	<0.001	5.8 (0.8–17.1)	10.3 (2.3–18.1)	0.318
Collagen, median % pixel area (range)
Panel A	43.7 (1.1–84.2)	24.6 (2.3–68.2)	<0.001	27.0 (1.1–36.4)	53.9 (8.7–84.2)	0.008
Panel B	19.1 (4.5–37.1)	22.5 (5.0–33.2)	0.105	19.4 (12.4–37.2)	18.7 (4.5–29.2)	0.295
Panel C	18.2 (2.8–57.8)	30.1 (6.9–47.0)	0.004	32.4 (19.1–57.8)	10.9 (2.8–43.0)	0.007
Panel D	15.4 (5.7–47.7)	19.0 (8.8–61.3)	0.021	16.4 (12.1–32.0)	14.5 (5.7–47.7)	0.342

^a p Values according to Mann-Whitney U-test.

BT: Brachytherapy; EBRT: external beam radiotherapy.

Panels A–D represent different optical densities, A = highest density and D = collagen fibers with the lowest density.

Figure 1. Hematoxylin-eosin stained biopsies from the vaginal wall in healthy women with thick squamous cell epithelia with dermal papillae (A), and cervical cancer survivors with thin epithelia and dense connective tissue with signs of fibrosis and elastosis (B). Scale bar= 200 μm.

Figure 2. Autofluorescent elastin fibers under the basal membrane in the vaginal wall in healthy women (A), and thick aggregated elastin fibers scattered throughout the connective tissue in the cervical cancer survivors (B). Scale bar= 200 μm.