**4. Radiation therapy**

Radiation therapy can be delivered as


*Primary radiotherapy:* Primary radiotherapy involves the use of radiation therapy as the only modality of treatment either alone or in combination with chemotherapy which is used as a radiation sensitizer. Primary radiotherapy is used in the following situations: (1) women with unresectable, locally advanced disease; (2) women with resectable disease in whom the risk of surgical morbidity is unacceptably high and (3) women with medical risk factors that contraindicate primary surgical therapy.

*Adjuvant radiotherapy*: Early stage lesions of the lower genitourinary tract can be treated surgi‐ cally if resection can be accomplished with adequate negative margins and acceptable morbidity. Post‐operative radiotherapy/adjuvant radiotherapy is reserved for cases in which histopatho‐ logic analysis of the removed specimen reveals features suggesting a high risk of local recurrence**.**

*Neoadjuvant radiotherapy*: In advanced stage disease, sometimes neoadjuvant radiation is used before surgery to render an inoperable tumour operable and for preserving the organ.

*Palliative radiotherapy*: For women with distant metastatic disease at presentation, cure is unlikely and the aim of the treatment is to improve the quality of life. However, palliative radiotherapy is frequently used to palliate the symptoms of a painful bone metastasis, relieve features of raised intracranial tension in brain metastasis and relieve dyspnoea in superior vena cava obstruction.

#### **4.1. Techniques of radiation**

The two main modalities of irradiation are teletherapy (external beam radiation) and brachy‐ therapy. External beam irradiation is used to treat the whole pelvis including the uterus, cervix fallopian tubes and ovaries, parametria and the regional nodes. A linear accelerator is used to deliver mega voltage photons to treat the whole pelvis. Gamma rays from a cobalt‐60 machine are also used to deliver radiation.

Brachytherapy: In this modality, source of radiation is placed inside the body as close to the tumour as possible. It usually consists of the placement of intrauterine and vaginal applica‐ tors. These are then loaded with the source of radiation. Cesium‐137 (<sup>137</sup>Cs) is the most popu‐ lar low‐dose rate (LDR) source and Iridium‐192 (192Ir) is the most common high‐dose rate source (HDR). Treatment with HDR is usually completed in a few minutes, whereas an LDR source takes 1 or 2 days to complete the treatment.

#### **4.2. Technique of external beam radiation**

External beam radiation in the treatment of carcinoma cervix aims at treating the whole pelvis. Whole pelvis involves treating the pelvic organs uterus, adnexa and upper third of vagina, parametrial tissues (cardinal, uterosacral and pubo‐cervical ligaments) and pelvic lymph nodes (internal and external iliac, obturator and pre‐sacral lymph nodes). Traditionally, the whole pelvis is treated with four fields—anterior‐posterior portals and two lateral fields (**Figure 3A** and **B**)]. Upper border is placed at L4‐L5 interspace to adequately cover the exter‐ nal iliac and lower common iliacs. The lower border is kept 3 cm below the lower extent of the tumour or lower border of obturator foramen if the vagina is not involved by the tumour.

**Figure 3.** (**A**) Anterior field borders, (**B**) lateral field borders, and (**C**) HDR brachytherapy dose distribution [pear‐shaped].

The lateral borders are kept 2 cm lateral to the pelvic brim in order to adequately cover the iliac nodes. The upper and lower borders of the lateral fields correspond with those of the AP‐PA fields. The anterior border is kept at the anterior border of the pubic symphysis and the posterior border is placed to cover the entire sacrum. High‐energy beams of the range of 6–15MV are used to deliver radiation. Dose of external beam radiation is 46 Gy in 23 fractions, 200 cGy per fraction and one fraction a day 5 days a week. The dose distribution of four field box plan is shown in **Figure 4A** and bladder and rectum contours are shown in **Figure 4B**.

**Figure 4.** (**A**) 3DCRT plan showing 95% coverage with four fields and **(B**) dose distribution of four field box plan showing 95% coverage with bladder and rectal contours.

#### **4.3. 3D planning techniques**

*Primary radiotherapy:* Primary radiotherapy involves the use of radiation therapy as the only modality of treatment either alone or in combination with chemotherapy which is used as a radiation sensitizer. Primary radiotherapy is used in the following situations: (1) women with unresectable, locally advanced disease; (2) women with resectable disease in whom the risk of surgical morbidity is unacceptably high and (3) women with medical risk factors that

*Adjuvant radiotherapy*: Early stage lesions of the lower genitourinary tract can be treated surgi‐ cally if resection can be accomplished with adequate negative margins and acceptable morbidity. Post‐operative radiotherapy/adjuvant radiotherapy is reserved for cases in which histopatho‐ logic analysis of the removed specimen reveals features suggesting a high risk of local recurrence**.** *Neoadjuvant radiotherapy*: In advanced stage disease, sometimes neoadjuvant radiation is used

before surgery to render an inoperable tumour operable and for preserving the organ.

*Palliative radiotherapy*: For women with distant metastatic disease at presentation, cure is unlikely and the aim of the treatment is to improve the quality of life. However, palliative radiotherapy is frequently used to palliate the symptoms of a painful bone metastasis, relieve features of raised intracranial tension in brain metastasis and relieve dyspnoea in superior

The two main modalities of irradiation are teletherapy (external beam radiation) and brachy‐ therapy. External beam irradiation is used to treat the whole pelvis including the uterus, cervix fallopian tubes and ovaries, parametria and the regional nodes. A linear accelerator is used to deliver mega voltage photons to treat the whole pelvis. Gamma rays from a cobalt‐60

Brachytherapy: In this modality, source of radiation is placed inside the body as close to the tumour as possible. It usually consists of the placement of intrauterine and vaginal applica‐ tors. These are then loaded with the source of radiation. Cesium‐137 (<sup>137</sup>Cs) is the most popu‐ lar low‐dose rate (LDR) source and Iridium‐192 (192Ir) is the most common high‐dose rate source (HDR). Treatment with HDR is usually completed in a few minutes, whereas an LDR

External beam radiation in the treatment of carcinoma cervix aims at treating the whole pelvis. Whole pelvis involves treating the pelvic organs uterus, adnexa and upper third of vagina, parametrial tissues (cardinal, uterosacral and pubo‐cervical ligaments) and pelvic lymph nodes (internal and external iliac, obturator and pre‐sacral lymph nodes). Traditionally, the whole pelvis is treated with four fields—anterior‐posterior portals and two lateral fields (**Figure 3A** and **B**)]. Upper border is placed at L4‐L5 interspace to adequately cover the exter‐ nal iliac and lower common iliacs. The lower border is kept 3 cm below the lower extent of the tumour or lower border of obturator foramen if the vagina is not involved by the tumour.

contraindicate primary surgical therapy.

vena cava obstruction.

72 Radiotherapy

**4.1. Techniques of radiation**

machine are also used to deliver radiation.

source takes 1 or 2 days to complete the treatment.

**4.2. Technique of external beam radiation**


of water mixed with 60 ml of Gastrovideo oral contrast within 1 hour, 24 hours prior to simula‐ tion. Only liquid diet will be allowed after that, till simulation. Domperidone 10 mg will be given.


While defining clinical target volume (CTV), gross tumour volume (GTV) along with cervix, uterine volume is added. Entire uterus is delineated in‐ cluding the fundus. CTV‐T includes the primary GTV‐T with potential mi‐ croscopic spread to cervix, uterus, parametrial tissues, upper vagina, and broad and proximal utero‐sacral ligaments. If posterior extension of cervical tumour is present, the entire utero‐sacral ligaments and upper pre‐sacral nodes are included. CTV‐N includes the pelvic lymph nodes, i.e. obturator, internal, external and common iliac, and upper pre‐sacral nodes. These are delineated by identifying contrast‐enhanced pelvic blood vessels on each CT scan and using a 7 mm margin to create a 3D CTV.A typical CTV to PTV margin of 10 mm is used around the CTV‐T to allow for organ mo‐ tion of cervix and uterus and measured set‐up uncertainties. For CTV‐N, organ motion occurs to a lesser extent and a 7–10 mm CTV to PTV margin is typically sufficient for set‐up variations. The contours of GTV, bladder and rectum are shown in (**Figure 5**).

**Figure 5.** Planning CT showing contours of GTV, bladder and rectum.

#### **4.4. Technique of brachytherapy**

of water mixed with 60 ml of Gastrovideo oral contrast within 1 hour, 24 hours prior to simula‐ tion. Only liquid diet will be allowed after that, till simulation. Domperidone 10 mg will be given. • CT Scan is taken from the first lumbar vertebra to 5 cm beyond the vaginal introitus. Intra‐ venous contrast is used to outline pelvic blood vessels to be used as surrogates for pelvic

While defining clinical target volume (CTV), gross tumour volume (GTV) along with cervix, uterine volume is added. Entire uterus is delineated in‐ cluding the fundus. CTV‐T includes the primary GTV‐T with potential mi‐ croscopic spread to cervix, uterus, parametrial tissues, upper vagina, and broad and proximal utero‐sacral ligaments. If posterior extension of cervical tumour is present, the entire utero‐sacral ligaments and upper pre‐sacral nodes are included. CTV‐N includes the pelvic lymph nodes, i.e. obturator, internal, external and common iliac, and upper pre‐sacral nodes. These are delineated by identifying contrast‐enhanced pelvic blood vessels on each CT scan and using a 7 mm margin to create a 3D CTV.A typical CTV to PTV margin of 10 mm is used around the CTV‐T to allow for organ mo‐ tion of cervix and uterus and measured set‐up uncertainties. For CTV‐N, organ motion occurs to a lesser extent and a 7–10 mm CTV to PTV margin is typically sufficient for set‐up variations. The contours of GTV, bladder and

nodes in CTV delineation.

rectum are shown in (**Figure 5**).

**Figure 5.** Planning CT showing contours of GTV, bladder and rectum.

• *Target volume definition*

74 Radiotherapy

The high tolerance of the uterus and vagina make it ideally suited for brachytherapy. In brachytherapy, sealed radioactive sources are used to deliver radiation at short distances. It is possible to deliver a high dose locally to the tumour with a rapid dose fall‐off from the surrounding normal tissues. The commonly used isotope for high‐dose rate brachytherapy includes Iridium 192 and Cobalt 60. Caesium 137 is used for low‐dose rate brachytherapy. Uterine tandem is inserted into the length of which depends on the length of the uterus. Two ovoids are placed in the fornices and the vagina is packed with gauze. This decreases the dose to the rectum and bladder. Using an after loading technique, the source is intro‐ duced into the ovoids and tandem. The dwell time and dwell position is calculated so that the desired dose to Point A is achieved. In JIPMER, the dose prescribed to Point A is 8.5 Gy × 3 using Iridium 192. The classical isodose for intra‐cavitary brachytherapy of carcinoma cervix is pear‐shaped (**Figure 3C**).

#### **4.5. JIPMER radiotherapy protocol for carcinoma cervix—summary (Table 5)**

The standard treatment for women with FIGO IB2, IIA, IIB, IIIA, IIIB and IVA disease is concurrent chemo‐radiation. Surgery is not preferred because of the increased risk of posi‐ tive margins and positive nodes. Concurrent chemo‐radiotherapy is preferred to radiation alone since the addition of concurrent chemotherapy confers an overall survival advantage [RR risk reduction is 29%] [13]. Platinum‐based chemotherapy is preferred over non‐plati‐ num‐based chemotherapy since there is more benefit with platinum‐based compounds (5FU). The hazard ratio (HR) for platinum is 0.70 (95% confidence interval, CI 0.61–0.80; *p*< 0.0001) compared to 0.81 (95% CI 0.56–1.16; *p*=0.20) for non‐platinum‐based chemo‐ therapy. 118 chemoradiation with cisplatin alone is comparable to chemo‐radiation with cisplatin/5‐fluorouracil. However, concurrent chemo‐radiation for treatment of cervical cancer is associated with increased acute toxicities specifically haematological and gastro‐ intestinal toxicity [13].

#### **4.6. RT for carcinoma cervix in special situations**

(1) Acute haemorrhage

Women presenting with acute episode of hemorrhage need to be hospitalised and stabilised with blood transfusion and vaginal packing

Broad spectrum antibiotics and antifibrinolytics are to be started.

Haemostatic RT—Whole Pelvis EBRT‐2 Gy/# standard fractionation as per stage‐wise treat‐ ment protocol. If bleeding persists, brachytherapy with ovoids will be considered.

(2) Pregnancy: First and second trimester pregnant women are managed by medical termi‐ nation of pregnancy as appropriate for gestational age by medical methods .This is fol‐ lowed by stage‐wise treatment after 2 weeks

Third trimester—Pregnancy is continued till 34 weeks with fetal monitoring and institution of steroids for fetal lung maturity followed by elective caesarean section. Stage‐wise treatment is undertaken after 4 to 6 weeks of caesarean section.


CD4 > 200 cells/ml—Stage‐wise treatment with radiotherapy + chemotherapy

CD4 50–200 cells/ml—Stage‐wise treatment with radiotherapy

CD4 < 50 cells/ml—palliation of symptoms

Use of universal aseptic precautions during P/V examination.


**Table 5.** JIPMER radiotherapy protocol for carcinoma cervix—summary.

### **4.7. Incidentally diagnosed carcinoma cervix after simple hysterectomy/Stump carcinoma after subtotal hysterectomy for benign disease**


(or)

Third trimester—Pregnancy is continued till 34 weeks with fetal monitoring and institution of steroids for fetal lung maturity followed by elective caesarean section. Stage‐wise treatment is

(3) Utero‐vaginal prolapse: Manual reduction during RT if possible; procedentia—prolapse

CD4 50–200 cells/ml—Stage‐wise treatment with radiotherapy

Use of universal aseptic precautions during P/V examination.

**2 Gy/#**

71.4 59.5 70–80 Gy

102.4 85.3 80–85 Gy

85.2 85.3

89.8 89.3

42.25

84 70

102.3 102.4

109.8 107.2

6 Gy× 3# linear applicator 96 80 85–90 Gy

6 Gy× 3# Linear applicator 96 80 85–90 Gy

No brachytherapy 39–50.7 32.5–

**Recommended dose to point A**

*>*85 Gy

85–90 Gy

**Stage EBRT ICBT‐HDR BED LQED at** 

Ovoid &tandem

8.5 Gy× 3#

8.5 Gy× 3# Ring &tandem or Ovoid &tandem

Vault brachytherapy

Ovoid &tandem or ring &tandem

Ring &tandem or ovoid &tandem

reduction under anaesthesia and labial stitching followed by RT.

CD4 > 200 cells/ml—Stage‐wise treatment with

CD4 < 50 cells/ml—palliation of symptoms

46 Gy/23# WP 8.5 Gy× 3#

undertaken after 4 to 6 weeks of caesarean section.

(4) HIV:HAART—Highly active anti‐retroviral treatment

radiotherapy + chemotherapy

IA1 0 7 Gy× 6#

IIB 45 Gy/20# WP

IIIA 46 Gy/23# WP

or

Or

46 Gy/23# WP

4 Gy/2#PM boost 6 Gy/3# PO

45 Gy/20# WP 4.5 Gy/2# PM‐Boost

46 Gy/23# WP 4 Gy/2# PM‐Boost

46 Gy/23# WP 4 Gy/2#PM boost 6 Gy/3# PO

30–39 Gy/10–13# (Palliative RT to gross disease)

**Table 5.** JIPMER radiotherapy protocol for carcinoma cervix—summary.

Post‐op 46 Gy/23# WP 8 Gy× 2#

IA2, IB1, IIA1, IB2, IIA2

76 Radiotherapy

IIIB <2/3 of upper vaginal involvement

IIIB >2/3 of upper vaginal involvement

IVA

status),

(Poor performance

Complete parametrectomy + upper vaginectomy + pelvic lymph node dissection *+* PA LN sampling followed by adjuvant RT or chemo RT as per the above indications

• Positive margins, gross residual disease—if imaging negative for nodal disease—chemo RT, if imaging positive for nodal disease—consider for surgical debulking of grossly en‐ larged nodes followed by chemo RT.

#### **4.8. Carcinoma of the endometrium protocol at JIPMER**

History and physical examination; biopsy report confirmation of carcinoma and type of carcinoma:


#### **4.9. The evidence present in treating endometrial cancer with radiotherapy**

In women with Stage I intermediate‐risk external beam pelvic radiotherapy reduces the local as well as vaginal recurrences. Vaginal brachytherapy alone also can achieve similar recur‐ rence rates in this group of women. In women with intermediate‐ to high‐risk group, the over‐ all survival is also similar with external pelvic beam radiation and vaginal brachytherapy. The role of chemotherapy combined with radiation not well established.
