*2.1.1 Vaginal applicators*

Various vaginal applicators are available in gynecologic oncology depending on the location of the radiation source and whether it contains a cover or not. The Fletcher-Suit-Delclos system is among the most commonly used (**Figure 1**). Vaginal ring applicators are mostly used in HDR. Cylinder vaginal applicators, i.e., Delclos dome cylinder are used in patients undergoing hysterectomy (**Figure 2**).

**Figure 1.** *Vaginal ring applicator.*

**Figure 2.** *Cylinder vaginal applicators (Delclos dome cylinder).*

#### *Translational Research in Cancer*

Single-channel cylinder applicator is among the most commonly used applicators; it minimizes the toxic effects as it is simple and since it covers the whole of the vaginal surface [12]. Multi-channel vaginal cylinder applicators are less harmful to neighboring tissues through providing asymmetrical dose radiation; however, they have a higher effect on the vaginal mucosa [13, 14].

Despite the presence of variable applicators, they have similar efficiency in the prevention of vaginal recurrence.

#### *2.1.2 Dose depth*

Despite the absence of a standard dose depth, vaginal lymphatics were reported to proceed 3 mm beneath the mucosa and treatment covering this depth was reported to be sufficient. Normally, a 1 cm depth is targeted. The most common monotherapy is a 0.5 cm depth and 7 Gy 3 fraction [12]. The doses effective in the vaginal surface when used as vaginal boost treatment have been reported by the Radiation Therapy Oncology Group [15].

#### *2.1.3 Vaginal length*

There is no consensus on the vaginal length to be treated. It has been reported that the proximal vagina can be treated between 1 and 10 cm [16]. The American Brachytherapy Society (ABS) has reported that the proximal vagina should be treated 3–5 cm or including 1/2–1/3 of the vagina [17]. Due to the possibility of high toxic doses causing vaginal stenosis and due to the decreasing frequency of distal vaginal recurrence, the treatment modalities that cover the whole vagina are gradually decreasing [12].

#### *2.1.4 Dose rate*

All vaginal brachytherapy applications had been carried out as LDR before the introduction of HDR [4]. Historically, low dose hourly 60 cGy had been used widespread in most brachytherapy regimens. This treatment modality given as LDR was taking long and it required hospitalization. About 96% of brachy therapists have switched to this method through the introduction of HDR applicators [17]. The advantages of HDR include less radiation exposure of the health staff and visitors as it enables remote control, thrombo-embolic events are less frequently encountered as the patients are treated in the outpatient setting and long-term immobilization is avoided. There is no difference between LDR and HDR with regard to recurrence and the overall survival [18].

#### *2.1.5 Treatment plan*

There are many ways for an accurate treatment plan in VB applications. When 2D and 3D CT-based treatment plans were compared, the 3D method was found to be superior as it reached the clinical target volume and produced less harm to neighboring tissues [19]. Many brachy therapists use the 3D treatment plan and its application at every session separately was not found to be superior to single session application, except for being expensive [20]. The CT-based treatment plan reveals the air between the vaginal cuff and the applicator effectively and enables a more effective treatment [21].

#### *2.1.6 Dose and duration of vaginal brachytherapy*

The toxic dose that emerges during VB is related to the amount of the total dose, dose velocity, total vaginal length, dose depth and the fraction time. In a study, the

**159**

*Brachytherapy in Endometrial Cancer*

*2.1.7 Protection from vaginal toxicity*

**3. Adjuvant vaginal brachytherapy treatment**

and related to the lower toxic effects.

**3.1 Adjuvant vaginal brachytherapy as monotherapy**

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

patients who received VB with HDR were allocated to four groups as 4 fractions of 9.0 Gy, 5 fractions of 6.0 Gy, 6 fractions of 5.0 Gy and 6 fractions of 4.5 Gy. A 1 cm depth from the vaginal surface was utilized. Vaginal, urinary bladder and rectal toxicity were found to increase as the amount of the dose increased along with the fraction [22]. In another study, no grade 2 or above vaginal, urinary bladder and rectal toxicity were encountered when 6 fractions of 4.0 Gy VB was applied targeted only to the vaginal surface [23]. The ABS recommends HDR VB as 24 treatment schemes as monotherapy and the 22 treatment scheme as boost dose [12]. In the PORTEC-4 study conducted for standardization of the dose and the fraction amount, the patients with H-I risk, early stage endometrial cancer were divided into treatment and observation groups; the treatment group was randomized as 3 fractions of 7.0 Gy or 3 fractions of 5.0 Gy. However, the study was terminated early as the patient collection and the untreated group were not proper. Therefore, further studies are required for standardization of the dose amount and the duration of fraction.

Vaginal toxicity is a significant complication of VB and it impairs the quality of sexual life due to vaginal atrophy, shortness and narrowness. The sexual activity frequency and satisfaction are reduced in patients undergoing surgery and VB [24]. In a study, having sexual intercourse during the VB treatment was reported to prevent vaginal shortness and narrowness; however, atrophy-related dyspareunia was reported in 2/3 of the patients and furthermore, it was emphasized that the distal 2/3 of the vagina was more susceptible to toxic effects rather than the proximal 1/3 of the vagina [22]. Use of vaginal dilator for 6 months following radiotherapy was shown to decrease the vaginal stenosis [25]. In the Cochrane database, use of vaginal dilator during radiotherapy was not shown to have sufficient evidence. However, it accepts the observational studies suggesting that use of the regular vaginal dilator may improve the vaginal stenosis rates reported by the patients [26]. Estrogen cream is another option for protection of the vagina. Despite the absence of sufficient and strong evidence about the use of estrogen creams, they were shown to prevent vaginal atrophy in small studies [27]. A selection should be made after discussing the benefits and harms of this treatment option with the patient.

As reported above, we know that pelvic EBRT reduces the recurrence; however, it leads to severe side effects compared to follow-up without treatment in endometrial cancer. Radiotherapy via the vaginal route was considered to be more proper as vaginal recurrences are seen most in post-operative endometrial cancer patients. Similarly, with pelvic EBRT, VB treatment was not shown to be effective on the overall survival. However, while the vaginal recurrence rate is 0–3.1% in VB, the pelvic recurrence rate is 0–4.1% [28–30]. These rates are similar with pelvic EBRT

In the randomized controlled PROTEC-2 study comparing the effectiveness of pelvic EBRT and VB treatment, all patients were H-I risk endometrial cancer patients who had undergone TAH + BSO, but not lymphadenectomy. The patients were allocated to three groups as the group that received 23 fractions 46 Gy as pelvic EBRT, the high dose rate (HDR) group that received 7 Gyx3 fractions and the low dose rate (LDR) group that received 30 Gy VB. While the 5-year vaginal recurrence

#### *Brachytherapy in Endometrial Cancer DOI: http://dx.doi.org/10.5772/intechopen.92703*

*Translational Research in Cancer*

prevention of vaginal recurrence.

Radiation Therapy Oncology Group [15].

*2.1.2 Dose depth*

*2.1.3 Vaginal length*

ally decreasing [12].

*2.1.5 Treatment plan*

*2.1.4 Dose rate*

have a higher effect on the vaginal mucosa [13, 14].

Single-channel cylinder applicator is among the most commonly used applicators; it minimizes the toxic effects as it is simple and since it covers the whole of the vaginal surface [12]. Multi-channel vaginal cylinder applicators are less harmful to neighboring tissues through providing asymmetrical dose radiation; however, they

Despite the presence of variable applicators, they have similar efficiency in the

Despite the absence of a standard dose depth, vaginal lymphatics were reported

There is no consensus on the vaginal length to be treated. It has been reported that the proximal vagina can be treated between 1 and 10 cm [16]. The American Brachytherapy Society (ABS) has reported that the proximal vagina should be treated 3–5 cm or including 1/2–1/3 of the vagina [17]. Due to the possibility of high toxic doses causing vaginal stenosis and due to the decreasing frequency of distal vaginal recurrence, the treatment modalities that cover the whole vagina are gradu-

All vaginal brachytherapy applications had been carried out as LDR before the introduction of HDR [4]. Historically, low dose hourly 60 cGy had been used widespread in most brachytherapy regimens. This treatment modality given as LDR was taking long and it required hospitalization. About 96% of brachy therapists have switched to this method through the introduction of HDR applicators [17]. The advantages of HDR include less radiation exposure of the health staff and visitors as it enables remote control, thrombo-embolic events are less frequently encountered as the patients are treated in the outpatient setting and long-term immobilization is avoided. There is no difference between LDR and HDR with regard to recurrence and the overall survival [18].

There are many ways for an accurate treatment plan in VB applications. When 2D and 3D CT-based treatment plans were compared, the 3D method was found to be superior as it reached the clinical target volume and produced less harm to neighboring tissues [19]. Many brachy therapists use the 3D treatment plan and its application at every session separately was not found to be superior to single session application, except for being expensive [20]. The CT-based treatment plan reveals the air between the vaginal

The toxic dose that emerges during VB is related to the amount of the total dose, dose velocity, total vaginal length, dose depth and the fraction time. In a study, the

cuff and the applicator effectively and enables a more effective treatment [21].

*2.1.6 Dose and duration of vaginal brachytherapy*

to proceed 3 mm beneath the mucosa and treatment covering this depth was reported to be sufficient. Normally, a 1 cm depth is targeted. The most common monotherapy is a 0.5 cm depth and 7 Gy 3 fraction [12]. The doses effective in the vaginal surface when used as vaginal boost treatment have been reported by the

**158**

patients who received VB with HDR were allocated to four groups as 4 fractions of 9.0 Gy, 5 fractions of 6.0 Gy, 6 fractions of 5.0 Gy and 6 fractions of 4.5 Gy. A 1 cm depth from the vaginal surface was utilized. Vaginal, urinary bladder and rectal toxicity were found to increase as the amount of the dose increased along with the fraction [22]. In another study, no grade 2 or above vaginal, urinary bladder and rectal toxicity were encountered when 6 fractions of 4.0 Gy VB was applied targeted only to the vaginal surface [23]. The ABS recommends HDR VB as 24 treatment schemes as monotherapy and the 22 treatment scheme as boost dose [12]. In the PORTEC-4 study conducted for standardization of the dose and the fraction amount, the patients with H-I risk, early stage endometrial cancer were divided into treatment and observation groups; the treatment group was randomized as 3 fractions of 7.0 Gy or 3 fractions of 5.0 Gy. However, the study was terminated early as the patient collection and the untreated group were not proper. Therefore, further studies are required for standardization of the dose amount and the duration of fraction.
