**5. Treatment**

**4. IGABT procedure (Kobe University Hospital)**

To perform more appropriate IGABT, appropriate anesthesia is very important. There are four types of anesthesia and combinations as follows: general anesthesia, lumbar subarachnoid spinal nerve block, sacral epidural block, and intravenous sedation. Intravenous sedation

**Figure 2.** HR-CTV (pink and outer line) and GTV (red and inner line) of extensive disease delineated on axial image

**Figure 1.** HR-CTV (pink and outer line) and GTV (red and inner line) of limited disease delineated on axial image

**4.1. Anesthesia**

(original) and coronal image (reconstructed).

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(original) and coronal image (reconstructed).

### **5.1. Treatment schedule and details of EBRT**

The Japanese protocol for EBRT and BT for cervical cancer is shown in **Table 2a**. Most institutions, including Kobe University Hospital, still use this protocol. Most patients are treated with 3D conformal pelvic irradiation (PI), with a total dose of 50.4 Gy in 28 fractions. At first, whole pelvic irradiation (WPI) is performed, and then WPI with a CS technique is performed. Generally, BT is initiated at the end of the WPI period and before the start of PI with a CS technique. Most patients are treated with three or four sessions of BT given once or twice a week. Regarding combined WPI and CS technique, 30.6 Gy in 17 fractions of WPI and 19.8 Gy in 11 fractions with CS technique are used for International Federation of Gynecologists and Obstetricians (FIGO) stage IB to IIB disease. For more advanced disease, 41.4 Gy in 23 fractions of WPI and 9.0 Gy in 5 fractions with CS technique are used. Paraaortic regional irradiation is added for patients with gross metastases. For lymph node metastases, an additional 10 Gy in 5 fractions is usually applied to each metastatic region.

In contrast with the Japanese protocol, many foreign institutions such as Medical University of Vienna deliver EBRT consisting of 45 Gy in 25 fractions without using a CS technique; at the end of EBRT, 4 fractions of BT are administered. IMRT is usually performed. The treatment schedules at representative institutions are also shown in **Table 2b** for direct comparison with the Japanese protocol. CS technique is not used by all institutions [8–12].

#### **5.2. Treatment planning for BT**

#### *5.2.1. Applicator reconstruction*

Fusion of CT and MR images is necessary for BT treatment planning, even for MRI-based IGABT, if the positions of the sources cannot be identified correctly due to the lack of simulated sources compatible with MRI (**Figure 3a**). To achieve true MRI-based treatment planning, home‐made catheters using flexible tubes filled with normal saline solution for interstitial BT that were compatible with MRI were used as simulated sources (**Figure 3b**). Using these catheters, positions of the sources could be described very clearly. By using the system included in the Oncentra Brachy applicator placement technique and these catheters, it is possible to achieve true MRI-based treatment planning for patients treated with IC-BT (**Figure 4**).

#### *5.2.2. Delineation of target and OAR*

The GTV and HR-CTV are delineated based on the recommendations from GYN GEO-ESTRO [1]. The intermediate risk clinical target volume (IR-CTV) is automatically delineated with a 5–15 mm margin from the HR-CTV, excluding the OAR.


Notes: WPI: whole pelvic irradiation, CS: central shielding, HDR-BT: high dose rate brachytherapy.

**Table 2a.** Details of Japanese treatment protocol for cervical cancer.

Image‐Guided Adaptive Brachytherapy for Cervical Cancer Using Magnetic Resonance Imaging: Overview.... http://dx.doi.org/10.5772/67382 95


Notes: WPI: whole pelvic irradiation, CS: central shielding, HDR-BT: high dose rate brachytherapy, HRCTV: high risk clinical target volume.

**Table 2b.** Details of treatment protocols for cervical cancer at the representative institutions.

with 3D conformal pelvic irradiation (PI), with a total dose of 50.4 Gy in 28 fractions. At first, whole pelvic irradiation (WPI) is performed, and then WPI with a CS technique is performed. Generally, BT is initiated at the end of the WPI period and before the start of PI with a CS technique. Most patients are treated with three or four sessions of BT given once or twice a week. Regarding combined WPI and CS technique, 30.6 Gy in 17 fractions of WPI and 19.8 Gy in 11 fractions with CS technique are used for International Federation of Gynecologists and Obstetricians (FIGO) stage IB to IIB disease. For more advanced disease, 41.4 Gy in 23 fractions of WPI and 9.0 Gy in 5 fractions with CS technique are used. Paraaortic regional irradiation is added for patients with gross metastases. For lymph node metastases, an additional 10

In contrast with the Japanese protocol, many foreign institutions such as Medical University of Vienna deliver EBRT consisting of 45 Gy in 25 fractions without using a CS technique; at the end of EBRT, 4 fractions of BT are administered. IMRT is usually performed. The treatment schedules at representative institutions are also shown in **Table 2b** for direct comparison with

Fusion of CT and MR images is necessary for BT treatment planning, even for MRI-based IGABT, if the positions of the sources cannot be identified correctly due to the lack of simulated sources compatible with MRI (**Figure 3a**). To achieve true MRI-based treatment planning, home‐made catheters using flexible tubes filled with normal saline solution for interstitial BT that were compatible with MRI were used as simulated sources (**Figure 3b**). Using these catheters, positions of the sources could be described very clearly. By using the system included in the Oncentra Brachy applicator placement technique and these catheters, it is possible to

achieve true MRI-based treatment planning for patients treated with IC-BT (**Figure 4**).

**FIGO stage, tumor size WPI (Gy) CS technique (Gy) HDR‐BT (to point A)** Ib1, II (small) 20 30 6 Gy × 4 fractions Ib2, II (large), III 30 20 6 Gy × 4 fractions

IVA 40 10 6 Gy × 3 fractions

Notes: WPI: whole pelvic irradiation, CS: central shielding, HDR-BT: high dose rate brachytherapy.

The GTV and HR-CTV are delineated based on the recommendations from GYN GEO-ESTRO [1]. The intermediate risk clinical target volume (IR-CTV) is automatically delineated with a

40 10 6 Gy × 3 fractions

50 0 6 Gy × 2 fractions

Gy in 5 fractions is usually applied to each metastatic region.

**5.2. Treatment planning for BT**

*5.2.2. Delineation of target and OAR*

5–15 mm margin from the HR-CTV, excluding the OAR.

**Table 2a.** Details of Japanese treatment protocol for cervical cancer.

*5.2.1. Applicator reconstruction*

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the Japanese protocol. CS technique is not used by all institutions [8–12].

The rectum, bladder, sigmoid colon, and small bowel are delineated using MR images. The bladder is usually filled with 100 mL of normal saline solution to avoid high doses to the small bowels before the acquisition of images. If necessary, the urethra is also delineated.

**Figure 3.** (a) MR images for treatment planning without simulated sources. (b) MR images for treatment planning with simulated sources consisting of flexible tube for interstitial BT.

#### *5.2.3. Treatment aim for dosimetric parameters*

#### *5.2.3.1. HR‐CTV*

The most important dosimetric parameter of the target is the HR-CTV D90. Our primary treatment aim is that the HR-CTV D90 should be more than 7.0 Gy per implant with a total of 70–80 Gy equivalent dose in 2 Gy fractions (EQD2) calculated by using the following formula:

$$\text{EQD2} \quad = \text{ } \text{ } n^\* d^\* \left( \left( d \, + \alpha/\beta \right) / \left( 2 \, + \alpha/\beta \right) \right) \tag{1}$$

where *n* is the number of fractions, *d* is the single fraction dose, tumor *α*/*β* = 10, normal tissue *α*/*β* = 3.

Total HR-CTV D90s calculated from the single fraction dose and the number of fractions of IGABT and WPI are shown in **Table 3a**. Doses for pelvic irradiation with the CS technique are not included. At other representative institutions, the total HR-CTV D90 is usually aimed at more than 85 Gy in EQD2. In previous reports, Nomden et al. reported that the mean HR-CTV D90 in EQD2 was 84 Gy [9]. Simpson et al. reported that the mean HR-CTV D90 was 86.3 Gy [12]. Although our HR-CTV D90 per implant was equivalent to that in other institutions [8, 9],


Notes: HR-CTV: high risk clinical target volume, EQD2: equivalent dose in 2 Gy fractions, IGABT: image-guided adaptive brachytherapy, WPI: whole pelvic irradiation.

**Table 3a.** Total HR-CTV D90 (EQD2) calculated from the single dose and number of fractions of IGABT and WPI.

the goal of total D90 was set lower because the use of the CS technique might hinder delivery of higher D90.

#### *5.2.3.2. OAR*

*5.2.3. Treatment aim for dosimetric parameters*

The most important dosimetric parameter of the target is the HR-CTV D90. Our primary treatment aim is that the HR-CTV D90 should be more than 7.0 Gy per implant with a total of 70–80 Gy equivalent dose in 2 Gy fractions (EQD2) calculated by using the following formula: EQD2 = *n* \* *d* \* ((*d* + *α*/*β*)/(2 + *α*/*β*)) (1)

**Figure 4.** MRI-based treatment planning of intracavitary BT using simulated sources and applicator placement technique.

where *n* is the number of fractions, *d* is the single fraction dose, tumor *α*/*β* = 10, normal tissue

Total HR-CTV D90s calculated from the single fraction dose and the number of fractions of IGABT and WPI are shown in **Table 3a**. Doses for pelvic irradiation with the CS technique are not included. At other representative institutions, the total HR-CTV D90 is usually aimed at more than 85 Gy in EQD2. In previous reports, Nomden et al. reported that the mean HR-CTV D90 in EQD2 was 84 Gy [9]. Simpson et al. reported that the mean HR-CTV D90 was 86.3 Gy [12]. Although our HR-CTV D90 per implant was equivalent to that in other institutions [8, 9],

*5.2.3.1. HR‐CTV*

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*α*/*β* = 3.

For the OAR, D2cc is recognized as the most important dosimetric parameter. In clinical IGABT, bladder, rectum, sigmoid colon, and small bowel D2cc must be calculated and recorded for every implant. The proposed upper limit of the total bladder dose is 85 Gy with a maximum of 90 Gy in EQD2. Those of the total rectum, sigmoid colon, and small bowel are 70 Gy with a maximum of 75 Gy in the EQD2. The upper limit of single OAR doses (non-EQD2) in IGABT calculated from the total OAR D2cc and WPI dose are shown in **Table 3b**. Doses from PI with the CS technique are not included. As for these OARs, many previous studies used similar criteria [8–10, 12].


**Table 3b.** Upper limit of single OAR doses (non-EQD2) in IGABT calculated from the total OAR D2cc and WPI dose.

#### *5.2.4. Dose prescription and optimization*

#### *5.2.4.1. Intracavitary BT*

The basic treatment plan prescribed to point A according to Japanese guidelines is first created for every implant. The point A dose is 6.0 Gy. Then, graphical optimization is performed to achieve the treatment aim for both the HR-CTV and the OAR.

#### *5.2.4.2. Combined intracavitary/interstitial BT*

Similar to intracavitary BT, a basic plan prescribed to point A (6.0 Gy) is first created. Next, optimization of the intracavitary applicator is performed to reduce the doses to the OAR. Then, the interstitial needles are activated to increase the target coverage. Additional optimization is usually performed to achieve the treatment aim.

#### **5.3. Limitations of CT‐based planning**

In performing CT-based planning, the most important limitation is inaccurate delineation of the HR‐CTV. CT‐based delineation is often very different from MRI‐based delineation (**Figure 5**). The HR‐CTV D90 may be significantly affected by the difference in imaging modality at BT (MRI or CT). Hegazy et al. reported that CT-based HR-CTV contouring based on FIGO stage led to a large overestimation of the width and volume. They concluded that if only CT was available, a minimum two-third of the uterine height might be a good surrogate for the height of the HR-CTV [13]. Clinical gynecologic examination and acquisition of MR images just before the start of BT can help to improve the accuracy of delineation.

**Figure 5.** Comparison of CT-based and MRI-based delineation of HRCTV. CT-based delineation is quite large compared to MRI-based delineation.
