**4.2 Treatment-related toxicity from the use of radiation therapy for endometrial cancer**

In the literature, radiotherapy was shown to have been used in 60% of cervical cancers, 45% of endometrial cancers and 100% of vaginal cancers [59, 60]. Healthy cervical and uterine tissues are known to tolerate radiation therapy (RT) well. Although pregnancy is known to have occurred in women receiving 20–30 Gy RT for the uterus, an atrophic uterus improper for pregnancy develops in women



#### **Table 5.** *HDR dose table.*

**Table 6.** *EBRT and HDR dose schemas.* receiving 40–50 Gy. The toxic effect of RT depends on the age for ovaries; exposure to 20 Gy usually results in ovarian insufficiency in an adult woman. The influence of RT on the vagina depends on the location (superior, medial, inferior, posterior or the anterior wall). While the proximal vagina seems to be resistant to high doses (>100 Gy), the distal and the posterior walls are susceptible to atrophy and stenosis. While the rectum and the urinary bladder can be treated with low risk with 45–50 Gy RT, the small intestine shows severe toxic effects against <30 Gy, depending on the treated volume. These toxic effects of RT are known to be related to the treated tissue amount, fraction number and dose, previous surgeries, concurrent chemotherapies, co-morbid conditions and the smoking status [61].

Acute toxicity is defined as conditions that develop in the course of RT. Sub-acute toxicity is defined as conditions that develop between 4 and 12 weeks after termination of RT.

Late toxicity is defined as the irreversible reactions that develop 3 months after termination of the treatment.

#### *4.2.1 Genito-urinary (GU) system toxicity*

The patient is asked to come to the treatment with a full urinary bladder with the aim of moving away the bowels as the urinary bladder can tolerate RT relatively better than the bowels.

#### *4.2.1.1 Acute radiation cystitis*

This is among the most common RT-induced complications. The patients present with urinary symptoms (dysuria, frequency, urgency and nocturia). Infectious cystitis should be excluded. The symptoms usually recover spontaneously within 1–2 weeks. Genitor-urinary complaints were reported to be seen less frequently when adjuvant therapy was performed with intensity-modulated radiation therapy (IMRT) [62].

#### *4.2.1.2 Late genito-urinary toxicity*

This toxic effect of RT emerges as the urinary bladder epithelium and the micro-vascular circulation are affected. Fibrosis and collagen accumulate under the epithelium and the muscle layer, and the urinary bladder capacity decreases. This effect leads to over-activity and contraction of the urinary bladder resulting in urge incontinence. In the PORTEC-1 study, while grade 3–4 toxicity was not observed, the rate of grade 1–2 genito-urinary complication was 5% higher [11].

Hematuria and ulcer formation are the late GU findings. Recurrent urinary bladder stones may be formed. Ureto-vaginal or vesico-vaginal fistulae may also develop following brachytherapy [63].

#### *4.2.2 Gastro-intestinal (GI) toxicity*

Gastro-intestinal toxicity may develop during RT or later and impair the quality of life of the patients through leading to restrictions in the daily lives of the patients.

#### *4.2.2.1 Acute RT toxicity*

As the small intestine epithelium shows a rapid proliferation, it is affected to a higher extent by RT. While nausea and vomiting are seen at the beginning of the

**165**

*Brachytherapy in Endometrial Cancer*

*4.2.2.2 Late GI toxicity*

proctopathy.

*4.2.3 Vaginal toxicity*

treated with HDR VB alone in a study [23].

and may result in secondary infections.

*4.2.3.2 Vaginal ulceration and necrosis*

*4.2.3.1 Acute vaginal mucositis*

*4.2.3.3 Vaginal stenosis*

not much effective [67].

*DOI: http://dx.doi.org/10.5772/intechopen.92703*

treatment, abdominal cramps and diarrhea are experienced during the following 2–3 weeks. This effect is considered to result from the disappearance of small intestine crypts and the inability to restore them in a short while [64]. The acute effects in the colon include fecal urgency and tenesmus. Acute colonic problems are seen in approximately 50% of the patients who receive 45–50 Gy as adjuvant; however, acute grade 3 toxicity is lower than 3% [10, 30]. There are randomized studies reporting that these acute effects may be significantly reduced by using IMRT [65].

Late effects may develop between 6 months and several years in most patients. The pathophysiology includes chronic enteropathy with mucosal atrophy and loss of mucin-producing goblet cells. Fibrosis in the intestinal walls causes dysmotility and acute obstruction. There are no techniques that do not cause late intestinal complications, including IMRT. The late toxic intestinal effects include chronic diarrhea, malabsorption, recurrent ileus, mucosal ulcer, telangiectasias and rectal

Vaginal complications are commonly seen both during pelvic EBRT and VB. This toxic effect impairs the quality of life of the patients by leading to sexual dysfunction. Vaginal toxicity above grade 2 was not reported when the vaginal cuff was

Erythema and superficial ulcers develop as a result of vaginal surface epithelium injury in patients receiving brachytherapy. This leads to exudative vaginal discharge

This complication is particularly seen when interstitial brachytherapy is used for

This is a common late complication of both pelvic EBRT and VB. Dyspareunia is common due to reduced vaginal length. Vaginal stenosis and complete closure should be prevented to achieve a satisfactory follow-up. Stenosis usually develops 3–6 months after therapy. Vaginal dilators with proper thickness and length are used for the primary repair in these patients. While some authors propose that the use of vaginal dilators after RT reduces the stenosis, some others propose that it is

treatment of full-thickness vaginal mucosa involvement [66].

treatment, abdominal cramps and diarrhea are experienced during the following 2–3 weeks. This effect is considered to result from the disappearance of small intestine crypts and the inability to restore them in a short while [64]. The acute effects in the colon include fecal urgency and tenesmus. Acute colonic problems are seen in approximately 50% of the patients who receive 45–50 Gy as adjuvant; however, acute grade 3 toxicity is lower than 3% [10, 30]. There are randomized studies reporting that these acute effects may be significantly reduced by using IMRT [65].
