**5. Evidence‐based recommendation ESMO‐ESGO‐ESTRO consensus [14] (Table 6)**

#### **5.1. Normal tissue tolerance**

Organs at risk (OAR) in radiation therapy of endometrial cancer include the bladder, rectum, small intestine and the femoral heads.

Radiation therapy for endometrial cancer and tissue tolerance (**Table 7**).

*EBRT for endometrial cancer*: The technique almost similar as that of carcinoma cervix planning except that the AP/PA field upper border is placed at L5‐S1 junction. The pelvis is treated with EBRT to 45–50 Gy in 25–28 daily fractions using 6–18 MV photon beams. The target volume is defined by GTV of the entire uterus in inoperable cases. CTV includes vaginal cuff, obturator nodes, external, internal and common iliac nodes. Planning target volume (PTV) is calculated as CTV plus 0.5–1 cm or ITV (internal target volume) plus 0.5 cm.

*Brachytherapy delivers* high dose to the vagina while minimizing dose to organs at risk. A vagi‐ nal cylinder of largest feasible diameter is the most common applicator used. The radiation is delivered with low‐dose rate (LDR) or high‐dose rate (HDR) radiotherapy. 50–60 Gy is the LDR prescription to the surface over 60–70 h when used alone. When combined with EBRT, the prescription dose is reduced to 25–30 Gy. The HDR dose prescriptions recommended by the American Brachytherapy Society (ABS) for adjuvant endometrial cancer is as follows. Suggested doses of HDR alone (**Table 8A**) and suggested doses of HDR to be used with 45 Gy EBRT for adjuvant endometrial cancer (**Table 8B**).

#### **5.2. Carcinoma of the vulva**

In patients with early stage vulval cancer with high risk features, radiation is commonly delivered following surgery. In patients with locally advanced tumours, surgery will result in unacceptable morbidity and poor cosmetic outcome. Radiotherapy in combination with concurrent chemotherapy is used for 'organ preservation' and cure. Apart from biopsy confir‐ mation of vulval lesion, FNAC of clinically positive inguinal nodes is mandatory and all other investigations prior to RT as per other malignancies are undertaken.

*Normal tissue tolerance***:** Organs at risk (OAR) in radiation therapy of vulvar cancer include the bladder, rectum, small intestine and the femoral head similar to that of endometrial cancer and the tolerance of vagina is <75–80 Gy.

#### **5.3. RT planning techniques: simulation and field arrangements**


• Borders of AP field should include superiorly from mid‐sacroiliac joint to cover external and internal iliac nodes or L4‐L5 level to cover the common iliac nodes if internal or exter‐ nal iliac nodes appear suspicious or positive.

**5. Evidence‐based recommendation ESMO‐ESGO‐ESTRO consensus [14]** 

Organs at risk (OAR) in radiation therapy of endometrial cancer include the bladder, rectum,

*EBRT for endometrial cancer*: The technique almost similar as that of carcinoma cervix planning except that the AP/PA field upper border is placed at L5‐S1 junction. The pelvis is treated with EBRT to 45–50 Gy in 25–28 daily fractions using 6–18 MV photon beams. The target volume is defined by GTV of the entire uterus in inoperable cases. CTV includes vaginal cuff, obturator nodes, external, internal and common iliac nodes. Planning target volume (PTV) is calculated

*Brachytherapy delivers* high dose to the vagina while minimizing dose to organs at risk. A vagi‐ nal cylinder of largest feasible diameter is the most common applicator used. The radiation is delivered with low‐dose rate (LDR) or high‐dose rate (HDR) radiotherapy. 50–60 Gy is the LDR prescription to the surface over 60–70 h when used alone. When combined with EBRT, the prescription dose is reduced to 25–30 Gy. The HDR dose prescriptions recommended by the American Brachytherapy Society (ABS) for adjuvant endometrial cancer is as follows. Suggested doses of HDR alone (**Table 8A**) and suggested doses of HDR to be used with 45 Gy

In patients with early stage vulval cancer with high risk features, radiation is commonly delivered following surgery. In patients with locally advanced tumours, surgery will result in unacceptable morbidity and poor cosmetic outcome. Radiotherapy in combination with concurrent chemotherapy is used for 'organ preservation' and cure. Apart from biopsy confir‐ mation of vulval lesion, FNAC of clinically positive inguinal nodes is mandatory and all other

*Normal tissue tolerance***:** Organs at risk (OAR) in radiation therapy of vulvar cancer include the bladder, rectum, small intestine and the femoral head similar to that of endometrial cancer

• Photon energy of more than 6 MV is required for treatment. CT is required for measuring the depth of inguinal nodes. Patients are simulated with custom immobilizations. Supine, frog‐leg positions are preferred to reduce the bolus effect from skin folds, with full blad‐

• Radio‐opaque markers should be used to delineate vulva tumour, scars, palpable lymph

Radiation therapy for endometrial cancer and tissue tolerance (**Table 7**).

as CTV plus 0.5–1 cm or ITV (internal target volume) plus 0.5 cm.

investigations prior to RT as per other malignancies are undertaken.

**5.3. RT planning techniques: simulation and field arrangements**

nodes, extent of vaginal involvement if present and anal verge.

EBRT for adjuvant endometrial cancer (**Table 8B**).

and the tolerance of vagina is <75–80 Gy.

ders to reduce dose to small bowel.

**5.2. Carcinoma of the vulva**

**(Table 6)**

78 Radiotherapy

**5.1. Normal tissue tolerance**

small intestine and the femoral heads.




**Table 6.** Evidence‐based recommendation ESMO‐ESGO‐ESTRO consensus [14].


**Table 7.** Radiation therapy for endometrial cancer and tissue tolerance.


**Table 8A.** Suggested doses of HDR alone.

#### **5.4. Intensity‐modulated radiation therapy**

Intensity‐modulated radiation therapy (IMRT) improves conformality and eliminates matching problem between electrons and photons over 3DCRT (3D conformal radiation) for vulvar cancer.


**Table 8B.** Suggested doses of HDR to be used with 45 Gy EBRT for adjuvant endometrial cancer.

IMRT reduces the dose to bladder, rectum, small bowel and head of femur. Definitions of CTV and PTV in 3DCRT and IMRT are as follows: CTV should include 1‐cm margin including the entire vulvar region and the bilateral external iliac, internal iliac and inguinofemoral nodes. PTV should include 1 cm margin around CTV.

## **5.5. Dose prescriptions (Table 9)**

*Carcinoma of the vagina*: Colposcopy‐directed biopsy of the cervix and vulva to rule out pri‐ mary cervical and/or vulvar cancer is undertaken apart from other investigations prior to radiotherapy. In women with early and locally advanced vaginal cancer, radiation is often the sole treatment either alone or in combination with concurrent chemotherapy which is used as a radiation sensitizer. RT comprising both external beam irradiation and brachytherapy is the treatment of choice. Brachytherapy can be intra‐cavitary or interstitial depending on the depth of invasion. Intra‐cavitary brachytherapy is used to treat superficial lesions <5mm in depth from the vaginal surface. Interstitial brachytherapy is used to treat lesions involving >5mm of depth from the vaginal surface.

#### **5.6. Radiotherapy for vaginal cancer (Table 10)**

#### *5.6.1. RT planning techniques simulation and field arrangements*


#### *5.6.2. AP/PA field*

**5.4. Intensity‐modulated radiation therapy**

**Table 8A.** Suggested doses of HDR alone.

**OAR Dose limitations**

**Table 6.** Evidence‐based recommendation ESMO‐ESGO‐ESTRO consensus [14].

Advanced Stage III residual disease, Stage IVA Palliative RT/Chemotherapy

Femoral heads Dmax < 40 Gy

**Table 7.** Radiation therapy for endometrial cancer and tissue tolerance.

*Note*: V = volume of tissue receiving *n*% of Gy.

Bladder V80 < 15%, V75 < 25%, V65 < 50%

Small intestine V15 <120 cc, V45 < 195 cc

**Risk group Description Recommended management**

EBRT is recommended

without chemotherapy –

Chemotherapy is recommended

IIIA: Chemotherapy and EBRT to be considered IIIB: Chemotherapy and EBRT to be considered IIIC1: Chemotherapy and EBRT to be considered

**Serous and clear cell after comprehensive staging:** Consider chemotherapy; clinical trials are encouraged Stage IA, LVSI negative: Consider vaginal brachytherapy only

Stage ≥IB: EBRT may be considered in addition to chemotherapy, especially for node‐positive disease **Carcinosarcoma and undifferentiated tumours:**

Consider EBRT; clinical trials are encouraged

IIIC2: Chemotherapy and extended field EBRT to be considered

High Stage III endometroid, no residual

High Non‐endometroid (serous or clear

carcinosarcoma

cell or undifferentiated carcinoma or

disease

80 Radiotherapy

Rectum V50 < 50%, V60 < 35%, V65 < 25%, V75 <15%

Metastatic Stage IVB Palliative chemotherapy/RT/best supportive care

*Note*: The 5‐year risk of recurrence is 2–10, 20–25 and 30 % for low risk, intermediate risk and high risk, respectively [15].

**Number of HDR fractions Dose/fraction Dose‐specific point** 7 0.5 cm depth 5.5 0.5 cm depth 4.7 0.5 cm depth 10.5 Vaginal surface 8.8 Vaginal surface 7.5 Vaginal surface

Intensity‐modulated radiation therapy (IMRT) improves conformality and eliminates matching problem between electrons and photons over 3DCRT (3D conformal radiation) for vulvar cancer. Superior border will be placed at L5‐S1 and inferior border at 3–4 cm below the vaginal marker and lateral borders at 1.5–2cm of the true pelvic rim. If inguinal lymph nodes are to be treated, wide AP fields will be planned to cover inguinal regions with narrow posterior fields with 2:1 weighting.


**Table 9.** Dose prescriptions.


**Table 10.** Radiotherapy for vaginal cancer.

#### *5.6.3. Dose prescriptions*

EBRT dose of 46 Gy with brachytherapy dose of 25–30 Gy is recommended. EBRT boost to 64–70 Gy is used instead of brachytherapy for extensive lesions and those involving recto‐ vaginal septum.

#### *5.6.4. Normal tissue tolerance*

Organs at risk (OAR) in radiation therapy of vaginal cancer include the bladder, rectum, small intestine and the femoral heads **Table 11**.

#### **5.7. Carcinoma of the ovary**

The role of radiation is limited in carcinoma ovary. Whole‐abdomen radiation has been used, but its popularity has waned because of the favourable toxicity profiles of the current chemo‐ therapeutic regimens.

#### **6. Newer modalities**

Newer external radiation techniques, such as intensity‐modulated radiation therapy (IMRT), image‐guided radiation therapy (IGRT), stereotactic body radiotherapy (SBRT), proton therapy and PET‐CT‐guided radiation, have been tried in gynaecological cancers, but these require further validation.


**Table 11.** Tissue tolerance for vaginal RT.

*5.6.3. Dose prescriptions*

**Table 10.** Radiotherapy for vaginal cancer.

**Stage Therapy**

**Table 9.** Dose prescriptions.

82 Radiotherapy

**Stage I** Brachytherapy alone or combined with EBRT

*5.6.4. Normal tissue tolerance*

**5.7. Carcinoma of the ovary**

therapeutic regimens.

**6. Newer modalities**

require further validation.

intestine and the femoral heads **Table 11**.

vaginal septum.

EBRT dose of 46 Gy with brachytherapy dose of 25–30 Gy is recommended. EBRT boost to 64–70 Gy is used instead of brachytherapy for extensive lesions and those involving recto‐

brachytherapy boost, with concurrent chemotherapy is recommended

recommended. If the parametria are involved, treatment should include parametrial boost

Extracapsular extension or node positive 55–60 Gross residual 65–70

**Stage II** EBRT to the primary and pelvic lymph nodes along with brachytherapy boost is

**Setting Scenario Dose (Gy)** Preoperative 45–50 Post‐operative Microscopic residual 50

Definitive Concurrent chemoradiation 60–65

**Stage III–IV A** EBRT to the primary and pelvic lymph nodes along with parametrial boost and

Organs at risk (OAR) in radiation therapy of vaginal cancer include the bladder, rectum, small

The role of radiation is limited in carcinoma ovary. Whole‐abdomen radiation has been used, but its popularity has waned because of the favourable toxicity profiles of the current chemo‐

Newer external radiation techniques, such as intensity‐modulated radiation therapy (IMRT), image‐guided radiation therapy (IGRT), stereotactic body radiotherapy (SBRT), proton therapy and PET‐CT‐guided radiation, have been tried in gynaecological cancers, but these

#### **6.1. Intensity‐modulated radiation therapy (IMRT)**

The technique of IMRT was developed using inverse planning. Intensity of the beam will be modulated spatially with the help of multileaf collimators. The advantage of IMRT lies in the reduction of amount of radiation dose received by small bowel and bone marrow. The use of IMRT is still under evaluation for intact cervix cases, but has been validated in the post‐ operative setting. Gandhi et al. reported the toxicities of pelvic radiotherapy in 44 patients, of which 22 received 3DCRT and 22 received IMRT. IMRT resulted in significant reduction of gastrointestinal toxicities with comparable clinical outcome. Patients who received IMRT had fewer grade 2 and grade 3 gastrointestinal toxicities as compared with 3DCRT [16]. Du et al. evaluated the dosimetry, efficacy and toxicity of IMRT in advanced cervical cancer. IMRT pro‐ vided better target dose conformity and better sparing of small bowel, bladder and rectum. They concluded that IMRT resulted in improved dose distributions with significantly lower toxicities with comparable clinical outcome [17]. The dose distribution of IMRT is shown in **Figure 6**.

**Figure 6.** Dose distribution of IMRT showing 95% coverage.

#### **6.2. Image‐guided radiation therapy (IGRT)**

The definition of IGRT, as given by the American College of Radiology and American Society of Radiation Oncology practice guidelines, is a procedure that refines the delivery of thera‐ peutic radiation by applying image‐based target relocalization to allow proper patient reposi‐ tioning for the purpose of ensuring accurate treatment and minimizing the volume of normal tissue exposed to ionizing radiation [18]. It is particularly useful in cases with a large mobile uterus as seen in young women and with a concern regarding the position of the uterus in the planned radiation field.

#### **6.3. Stereotactic body radiotherapy (SBRT)**

SBRT delivers radiation with large fraction sizes using highly conformal treatment tech‐ niques. In isolated para‐aortic node cases, it has been considered for a nodal boost. It should not be used as replacement for brachytherapy due to the significant increase in normal tissue doses with SBRT as compared with brachytherapy.

#### **6.4. Proton therapy**

The rationale for proton therapy lies in the improvement of therapeutic ratio by reducing the radiation dose to non‐targeted tissues, thereby reducing toxicity and facilitating dose escala‐ tion to achieve increased tumour control. Proton therapy can offer the best way of sparing the small bowel and rectum and can contribute to significant decrease in acute and chronic toxicities in cervical cancer treatment.

#### **6.5. Image‐guided brachytherapy**

Currently, image‐guided adaptive brachytherapy in gynaecological malignancies is based on CT and MRI. Ultrasonography (USG) as an imaging modality for guidance is also being explored. Advantages of USG include easier availability, cost‐effectiveness and small learning curve which makes it highly useful in developing countries. Limited availability and acces‐ sibility to CT and MRI prevented the early adoption of these promising techniques. Potter et al. reported the clinical outcome of 156 patients treated with image‐guided brachytherapy. Ninety‐seven percent of patients achieved complete remission with 3‐year overall local con‐ trol rates of 95%, 3‐year overall cancer‐specific survival rates of 74% and 3‐year overall sur‐ vival rates of 68%. They concluded that there is reduction in major morbidity and pelvic recurrence with the use of image‐guided brachytherapy [19].

#### *Side effects of pelvic radiation:*

Radiation‐induced side effects depend on the type of tissue, dosage and methods of deliv‐ ery of radiation, and the manifestations can be acute and chronic. Acute side effects usually occur during or within the first 3 months of completing radiation. These include fatigue, skin irritation or redness of the skin and loose bowel movements discomfort when urinating. Chronic side effects occur 3 months after completion of radiation. It includes skin changes like thinning of skin, radiation enteritis which manifest as loose stools and bleeding per rectum, cystitis, vaginal stenosis and intestinal obstruction and perforation are other uncom‐ mon side effects. Common late toxicities include vaginal stenosis/shortening, dryness, fibrosis, telangiectasia, atrophy of skin. Fracture of femoral neck has been implicated with osteoporosis and smoking. Avascular necrosis of the femoral head, though extremely rare, may also occur. Infection, lymphocyst formation and lymphoedema have been associated with groin radiation. Psychosocial consequences which are related to sexual function and body image may occur. With 200 Gy, the rate of tissue necrosis is less than 1% for cervical tissue and vagina is more sensitive with a tolerance of 100–140 Gy, beyond which necrosis is common. The complication of vesicovaginal fistula may result beyond a threshold of 150 Gy and rectovaginal fistula at 80 Gy [5].

Nutrition is important and should contain high protein. Plenty of oral fluids intake of more than 3 litre is necessary to avoid dehydration. When EBRT is employed, skin is the most commonly affected tissue. Avoiding soap and other irritants is important to avoid ulceration.
