Radiotherapy in Cervical Cancer

Abstract

Radiotherapy plays a significant role in the management of cervix cancer. In recent decades, there have been several advancements in radiation therapy treatment techniques. Moving from conventional two-dimensional techniques to advanced techniques like 3D conformal radiation therapy (3D-CRT), intensity-modulated radiation therapy (IMRT), and volumetric modulated radiation therapy (VMAT) has led to improvement in the treatment outcomes. The aim of radiation therapy is achieved by these advanced techniques, which deliver optimal tumoricidal doses to tumor volumes and minimal doses to the normal tissues around the tumor and can reduce toxicity more effectively than the conventional techniques. These external beam radiotherapy (EBRT) techniques along with brachytherapy play a significant role in the treatment of gynaecological cancer. Compared to point-based dose brachytherapy planning, better local control and lower toxicity have been associated with advanced image-based brachytherapy.

1. Introduction

Cervical carcinoma is the fourth most common malignancy in women worldwide [1]. According to GLOBOCAN 2020 statistics, estimated new cases of cervix cancer worldwide are 604,127 (3.1%) estimated deaths are 341,831 (3.4%). In India, the incidence of cervix cancer is 123,907 (9.4%), while mortality in such cases is 77,348 (9.1%) [2]. Cervical cancer cases are predominant in Asia, Africa, and Central and South America due to lesser frequency of screening, multiparity, low-socioeconomic status, poor hygiene, low immunity and nutritional problems [3]. Most cases are in Africa because of fewer screening measures and the chances of immunodeficiency because of the human immunodeficiency virus (HIV). More than 90% of cervical cancers are related to human papillomavirus (HPV) infection and are sexually transmitted [4]. Intrauterine exposure to diethylstilbestrol (DES) is related to the development of adenocarcinoma.

Radiotherapy plays a significant role in the management of cervix cancer. The standard mode of definitive treatment in patients of locally advanced cervical carcinoma involves both components of radiotherapy: External beam radiotherapy (EBRT) and brachytherapy [5, 6].

2. Rationale for the use of radiotherapy in cervical cancer

To achieve excellent locoregional control (LRC), disease-free survival (DFS) and overall survival (OS), surgery or radiotherapy alone is recommended for FIGO stage I, with tumor size less than 4 cm. Radiotherapy alone has also helped to achieve excellent survival and pelvic disease control rates in patients with stage IB cervical cancer. Eifel et al. reported 5-year disease-specific survival and pelvic control rates of 90 and 98%, respectively, for 701 patients treated with radiation alone for stage IB1 disease [7].

Concurrent chemoradiotherapy (CCRT) is the standard treatment of choice for locally advanced cervical cancer (LACC) ((FIGO (International Federation of Gynecology and Obstetrics) stage IIB to IVA). The survival outcome with CCRT is better when compared to radiotherapy alone [8, 9, 10, 11].

3. External beam therapy

3.1 Indications and target volumes

External beam therapy (EBRT) is part of the routine treatment of Carcinoma Cervix FIGO stages IB2 to IVA and in some earlier stages if the patient is not fit for/willing for surgical treatment [12, 13]. In patients with an intact uterus, EBRT is planned to treat the primary tumour with its local extensions as determined by clinical examination and diagnostic imaging, i.e. Gross tumour Volume (GTV), along with the entire uterus, the cervix, 2–3 cm of vagina below the inferior most extent of the disease, the parametrium and uterosacral ligaments. This forms the Primary-Clinical Target Volume (CTV – P). EBRT also targets the draining lymph nodal groups, i.e. the pelvic group of lymph nodes, which includes the internal, external, common iliac nodes, obturator and presacral lymph nodes. This forms the Nodal—Clinical Target Volume (CTV – N). In certain cases, the para-aortic or inguinal group of lymph nodes may also be treated by EBRT [14, 15, 16].

Para-aortic group of lymph nodes may be treated electively in cases where multiple pelvic nodes are involved (i.e. > 2 pathological LN or involvement of common iliac region). Therapeutic para-aortic irradiation is done in FIGO stage IIIC2 patients. In patients where the lower one-third of the vagina is involved, i.e. FIGO stage IIIA, the inguinal group of nodes must also be treated electively [13].

When EBRT is administered in patients post-hysterectomy, the radiation field includes the CTV-P, which comprises the tumor bed and any possible uterosacral, parametrial, uterine extension, and the CTV-N. Indications of adjuvant EBRT could be the presence of intermediate-or high-risk pathological features such as lymphovascular space involvement or stromal invasion, the large size of the tumor, involvement of lymph nodes or parametria and gross/microscopic residual disease post-surgery [9, 17].

3.2 EBRT treatment techniques

3.2.1 Two-dimensional conventional radiotherapy technique

Conventionally, EBRT is planned and administered based on bony anatomy as seen on X-ray simulation and as per clinical judgment of tumour location and extension, i.e. 2-D treatment planning.

Since there is limited soft tissue contrast seen on radiographs, treatment planning is done based on knowledge of tumor position relative to bony landmarks and anatomical structures visible with the aid of contrast agents such as barium which may be used to visualize small bowel or lower extent of disease in the vagina. For the treatment of gynecological malignancies, patients are generally simulated in the supine position as it is easily reproducible and more comfortable for the patient. A prone position may also be used for obese patients to reduce radiation dose to the bowel. It is important to ensure that patients are simulated and treated daily with a full bladder to reduce bowel toxicity.

When anteroposterior (AP) patient thickness is <20 cm, patients are treated by two fields (AP-PA) (Figure 1(a) and (b)), and when AP thickness is >20 cm, patients are treated by four fields (AP-PA and bilateral, i.e. box field technique) (Figure 2(a) and (b)). Figures 1(b) and 2(b) represent Beam’s eye view for AP and AP-lateral field respectively. Box field technique is to be strongly considered for AP thickness > 20 cm and treatment on Cobalt teletherapy units. For conventional whole pelvic radiotherapy (WPRT), the superior border of the field is placed at L4-L5 interspace while the inferior border of the field is at the lower border of the obturator foramen or 2–3 cm below the vaginal extent of disease, whichever is lower. The lateral borders of the AP/PA field extend 1.5–2 cm lateral from the widest point of the pelvic brim. The lateral fields cover the sacral hollow posteriorly, extending 0.5–1 cm anterior to the pubic symphysis. Shielding blocks may be placed at the corners of the field to reduce the dose to the small bowel, femoral heads and sacrum.

Figure 1.

(a) Two field conventional AP-PA plan, (b) Beam’s eye view-AP field.

Figure 2.

(a) Four field conventional box-field plan (b) Beam’s eye view-AP and lateral.

For para-aortic field irradiation, the pelvic field may be extended superiorly uptoT12-L1 interspace, in continuation with the pelvic field, or a separate para-aortic field may be set up with a gap from the superior border of the pelvic field to maintain dose homogeneity. Four fields technique (including AP-PA and two lateral fields) are used to treat para-aortic nodal involvement to reduce small bowel dose. When the inguinal group of lymph nodes is to be irradiated, the lateral extent of the AP/PA fields is extended up to the greater trochanter. When indicated, a parametrial boost dose may be administered after making a midline shielding block, although this technique is largely being replaced by interstitial brachytherapy [18].

Even though modern guidelines recommend the use of CT/MRI/PET-based planning, due to resource constraints, several treatment centres in Low-Middle-Income Countries (LMIC) still use 2-D treatment planning.

3.2.2 Three-dimensional conformal radiotherapy

Several studies have shown that planning on CT/MRI gives better coverage of CTV-N and CTV-P as compared to 2-D treatment planning, where geographical blunders can quickly happen, especially for CTV-N. Thus, CT-based planning (along with the incorporation of MRI/PET when available, preferably taken with the patient in treatment position) has now become the standard for EBRT in cervical cancer treatment planning in most developed countries.

For 3D-Conformal Radiotherapy (3D-CRT), the patient is simulated after administration of intravenous contrast as the vasculatures serve as a surrogate for the delineation of CTV-N. At the time of CT simulation, radio-opaque markers are placed for identification of the vaginal extent of disease and at the introitus of the vagina and anal verge to help delineate normal structures. Patient position during simulation is as explained earlier. Administration of oral contrast 30 minutes before simulation may help in better delineation of the small bowel. The CTV-P, CTV-N and organs at risk (OARs) are contoured on the axial CT sections acquired at the time of simulation as per standard guidelines and the clinician’s judgment. Superiorly, the CTV-N extends from the bifurcation of the common iliac vessels as visualized on the CT scans, which may lie at a higher vertebral level compared to the conventionally placed superior border of the 2D technique. Inferiorly, CTV-N extends to cover the external iliac, internal iliac, presacral and obturator groups of lymph nodes. Planning target volumes (PTVs) are created for each CTV (CTV-P and CTV-N) as per institutional standards. The common organs at risks (OARs) used in treatment planning are the bowel, bladder, rectum and femoral heads.

Similar to the 2D treatment technique, the patient can be treated with two fields (AP-PA) (Figure 3(a) and (b)) or box fields (Figure 4(a) and (b)), arrangement of beams of 6 and/or 15 MV depending on the patient’s AP thickness and disease. When indicated, para-aortic/parametrial boost volumes may also be included in the planning volumes [18]. Figures 3(b) and 4(b) represent digitally reconstructed radiographs (DRR) of AP and AP-Lateral field respectively.

Figure 3.

(a) Two field AP-PA 3D-CRT plan (b) DRR- AP field.

Figure 4.

(a) Four field 3D-CRT plan (b) DRR- AP and lateral field.

Moderns LNACs are equipped with multileaf collimators (MLCs), which are small, individually motorized leaves that can be used to shape the treatment field and block normal tissues such as skin, soft muscle tissue, anterior small bowel, parts of anorectum to reduce normal tissue toxicity as compared to 2D treatment planning [18, 19].

3.2.3 Intensity-modulated radiation treatment

2D and 3D radiation techniques have several limitations, such as encompassing large volumes of normal tissues in the treatment fields, which leads to several acute and long-term complications such as gastrointestinal, hematological and genitourinary complications and also the difficulty to deliver higher doses higher and potentially more efficacious doses to select patients at increased risk of recurrence, for example, those with involved lymph nodes and gross unresectable disease [20, 21].

The use of Intensity Modulated Radiation Therapy (IMRT)/Volumetric Modulated Arc Therapy (VMAT) is now being recommended by international guidelines for EBRT for cervical cancer as several studies have shown reduced treatment-related toxicities and improved survival for patients treated with these treatment techniques. With the aid of IMRT, it is possible to deliver complex dose distributions for target volumes and facilitate rapid dose fall-off outside the target volume. Unlike the convex-shaped dose distribution given by a 3D-CRT plan, an IMRT plan involves the superposition of multiple-segmented fields from different directions, which results in a dose distribution that is concave in shape around the OARs when PTVs are in close proximity to them thus aiding in reducing the dose delivered to the former [22].

When patients with intact uterus are planned for IMRT treatment, patients are simulated with a full bladder as well as an empty bladder, and both the CT simulations films are fused to estimate internal target volume (ITV) margins. Custom immobilization devices such as body mold that fixes the position of the upper body, trunk and proximal legs are recommended to reduce set-up error. After CT simulations and contouring of target volumes and organs at risk on axial sections, multiple (5–7) non-coplanar treatment beams are placed for the IMRT process, which could be placed manually by treatment planners or could be automatically shown in Figure 5. The next steps in IMRT treatment planning involve determining the plan objectives, i.e. target dose and coverage and normal tissue doses, followed by optimization of intensity distribution, dose calculation by inverse planning and treatment plan evaluation. MLCs shape or modulate the intensity of the treatment field and help in the delivery of IMRT while improving the therapeutic ratio [19].

Figure 5.

IMRT of cervix cancer with beam arrangement.

3.3 Image-guided radiotherapy

Image-guided Radiotherapy (IGRT) is recommended along with IMRT/VMAT to limit PTV margins and ensure safe dose delivery. IGRT is important for target delineation as well as for treatment delivery. The most commonly used IGRT treatment delivery technology is electronic portal devices (EPIDs), followed by kilovoltage (kV) and megavoltage (MV) CBCT and helical tomotherapy. IMRT/VMAT can also be used to safely deliver boost doses to pathological pelvic or para-aortic lymph nodes safely as compared to 3D-CRT. IMRT-SIB can be used in such patients, i.e. FIGO stage IIIC to deliver adequate doses without increasing overall treatment times (OTT). EBRT delivered by IG-IMRT in adjuvant settings has reduced toxicity with no difference in disease outcomes. Although IMRT is not considered an alternative to brachytherapy, in certain patients where brachytherapy is not an option due to the extensive nature of the disease, IMRT/SBRT boosts have been used as a last resort [23, 24].

3.4 Radiation dose and treatment schedule

Patients are treated by EBRT to a dose of 45Gy/25 fractions or 46Gy/23 fractions [13]. An additional boost dose of up to 60 Gy can be delivered to grossly involved nodes. A parametrial boost of 5–10 Gy may be given to bulky parametrium/pelvic sidewall disease after completion of WPRT [13, 25].

When treating with curative intent, EBRT should include concurrent cisplatin-based chemotherapy administration, as several trials and meta-analyses have shown benefits in locoregional control as well as overall survival [26]. EBRT is followed by brachytherapy for optimal tumor control.

3.5 Role of EBRT in salvage and palliative

In patients with locoregional recurrent disease, CTRT can be offered to radiotherapy naïve patients. EBRT can be combined with brachytherapy in pelvic centrally recurrent disease.

Palliative EBRT may be given to patients with painful local disease, symptomatic bone metastases or vaginal bleeding [13].

4. Brachytherapy

Brachytherapy is a technique to deliver radiation at a short distance using an encapsulated source. The sources are placed close to or into the treatment volume. It can be delivered in different ways. The most common technique used in the treatment of cervical cancer is intracavitary brachytherapy. In cases where intracavitary brachytherapy is not feasible, interstitial brachytherapy is used for the treatment. These techniques have been discussed below.

4.1 History of brachytherapy

In the beginning, radium was the only radionuclide used for intracavitary treatment, which was later discontinued due to reasons concerning radiation safety. It was replaced with other radionuclides like Cs-137, Ir-192 and Co-60. Ir-192 and Co-60 are the most popular gamma-emitting source used in ICBT. Initially, manual after-loading techniques were used for the treatment, which caused radiation exposure to the personnel involved in the procedure, but with the introduction of remote after-loading units, the personnel exposure was eliminated. These machines have a mechanism to move and retract the source automatically. The source moves in steps and irradiates each position for a planned dwell time. The dose rate has been a crucial parameter in determining the impact of radiation on target and normal structures.

Low-dose rate brachytherapy machines with Cs-137 sources have been used for the treatment of cervix cancer for decades. However, they have gradually been phased out due to high patient bulk and lengthy treatment duration. The use of high dose rate (HDR) machines for intracavitary brachytherapy treatment has increased due to several advantages like shorter treatment time, increased patient treatment, etc. Due to these profound differences, HDR machines have become predominant worldwide.

In earlier times, when treatment planning was not based on computers and computation of absorbed dose was limited, to determine the number of sources, their arrangement, strength and the dose distribution, it was necessary to define some rules. Therefore, different dosimetric systems were developed for brachytherapy. Stockholm system in 1914, the Paris system (1919) and the Manchester system in (1938) were the systems used for intracavitary brachytherapy [27]. However, Stockholm and Paris systems did not gain popularity as they were based on the description of absorbed dose based on mg-hrs of radium used and did not assess absorbed dose well in tumors and organs at risk. Manchester system came to be used worldwide as it involved clear specification of absorbed dose at point A and to critical structures.

With the introduction of the Manchester system, the concept of absorbed dose point prescription came into existence. The purpose of dose points was to obtain a method of dose prescribing and reporting which was reproducible on orthogonal radiographs in terms of anatomy or applicator. Taking this into consideration, Point A was defined by Tod and Meredith in 1938, and was later modified in 1953 [28]. They defined it as a point located 2 cm superior to the last intrauterine source and 2 cm lateral to the cervical canal. Manchester system also considered Point B, which represented the dose to internal iliac and obturator lymph nodes. Since the bladder and rectum were the critical structures that were most affected during ICBT of cervix cancer, it was necessary to record the doses received by them. Therefore, besides the point A dose, the dose to bladder and rectum points, pelvic wall point [29] and lymphatic trapezoid [30] were also estimated. The doses to points representing the bladder and rectum were recommended to be below 80% of the dose prescribed to Point A.

4.2 Treatment techniques

4.2.1 Intracavitary brachytherapy (ICBT)

Intracavitary brachytherapy (ICBT) is a technique where sources are placed in body cavities [31]. It has been widely used in the treatment of gynecological malignancies [32]. The technique employs specific applicators inserted in the uterus and vagina to deliver high-dose radiotherapy [33] by creating a volumetric dose distribution around the tumor. It has an important role in the management of cervical cancer. ICBT can be used either solely for treatment in the early stages or in combination with EBRT (locally advanced cases). Since a very high dose to the primary cervical tumor and a relatively lower dose to the nearby critical structures can be delivered by ICBT, better local control and less toxicity can be achieved using intracavitary brachytherapy [34, 35, 36]. In fact, a decline in survival rates has been observed in patients where brachytherapy after EBRT is not given [37, 38]. Therefore, ICBT becomes a necessary part of the whole treatment regime. Ir-192 is the most common source used for HDR brachytherapy in cervical cancer. However, recently, Co-60-based HDR brachytherapy has gained popularity for ICRT in cervix cancer as it reduces the cost of frequent source replacement due to its longer half-life [39].

4.2.2 Interstitial brachytherapy

It is a method where radioactive sources are implanted directly into the tumor tissue. This technique can be used in sites where head and neck, prostate and soft tissue sarcoma. In cervical carcinoma cases where intracavitary technique is not feasible due to various factors such as involvement of medial parametrium, bulky tumor (size >4 cm) and recurrent disease, interstitial brachytherapy is a preferred technique [40]. Interstitial implants use trans-perineal [41] or trans-vaginal templates [42]. Martinez Universal Perineal Interstitial Template (MUPIT) is one such template designed to deliver brachytherapy doses [43]. Dose prescription points in interstitial brachytherapy are defined using the rules of Paris system.

4.3 Image-based brachytherapy

4.3.1 Two-dimensional image-based brachytherapy

Initially, applicators used in the Manchester system consisted of two ovoids, an intrauterine tube (made of rubber), and a low-dose-rate brachytherapy machine were used for treatment. However, with the evolution in technology, the HDR machines and modern applicators like Fletcher Williamson stainless steel applicators consisting of two ovoids (diameter 20, 25 and 30 mm) and a uterine tandem (angles 15°, 30° and 45°) came into existence (Figure 6).

Figure 6.

Fletcher Williamson applicator.

In the ICRT technique, the tandem is inserted in the uterine canal, and ovoids are placed in vaginal fornices in OT. After the completion of the application, treatment planning of patients is done on anterior-posterior and lateral orthogonal x-ray images in the treatment planning system (TPS). This involves reconstruction of the applicator, loading the source positions and calculation of the doses to Point A, ICRU bladder point and ICRU rectal points. Reporting doses to ICRU bladder and ICRU rectal points are recommended by ICRU report 38 [44]. The ICRU bladder point is identified with the help of a contrast-filled Foley’s bulb. While ICRU rectal point was defined as 5 mm behind the posterior vaginal wall, which was localized with the help of a rectal retractor containing radiopaque material. In addition to these points, the dose to two other points, which are 1.5 cm superior and inferior to the ICRU bladder points should also be recorded. In a study by Srivastava et al. [45], it was observed that the dose at a point 1.5 cm above the ICRU bladder point was higher than the ICRU bladder point dose. This means that the ICRU bladder point is not the true representation of the maximum point dose to the bladder (Figure 7). A three-dimensional pear-shaped isodose distribution is obtained and displayed in the TPS. A dose of 7 Gy per fraction for three fractions is prescribed in brachytherapy treatment. Optimization is done by changing dwell positions in plans where bladder or rectum doses are observed to be high. These plans are then exported to the treatment console for treatment on a brachytherapy machine.

Figure 7.

Lateral and AP radiograph showing ICRU bladder and ICRU rectum point.

Treatment planning on 2D images, however, has limitations. The target volume could not be delineated, so the clinical target volume (CTV) covered by the reference isodose could not be identified. Moreover, maximum doses to the organs at risk, such as bladder and rectum, could not be evaluated as 2D image-based treatment planning gave information about only the point doses to these OARs, which was insufficient to predict the toxicities. This gave path to the need to express dose distribution in three dimensions (3D), giving rise to the emergence of 3D image-based brachytherapy.

4.3.2 Three-dimensional image-based brachytherapy

In earlier decades, two-dimensional imaging (orthogonal radiographs) was widely used for treatment planning in brachytherapy. This treatment planning method provided limited information about the tumor dimensions and dose to the target and OARs. Since this method relied on point-based dose prescription, it resulted in under dosage in case of bulky tumors and overdosage in small tumors. With the advent of 3D imaging modalities like CT, MRI and USG, knowing the true extent of a tumor has become easy. 3D imaging helps in tumor volume assessment and delineation of OARs.

Image-based brachytherapy gives a basis for understanding the relationship between absorbed dose and volume. 3D image-based planning helps in the evaluation of dose-volume parameters and their correlation with clinical results. It is useful for individualization of dose distribution as per patient’s anatomy and tumor extent with the help of the information obtained from the dose-volume histogram (DVH). This helps improve the coverage of the target and reduce the dose to OARs.

In 2005, recommendations on terms and parameters used in 3D image-based brachytherapy were published by the GYN GEC-ESTRO Working Group, which emphasized the use of sectional imaging for tumor volume assessment. After a year, the Working Group developed another guideline that focused on 3D dose-volume parameters in treatment planning. Instead of point, the volume-based prescription was used, and dose to target and OARs were evaluated in terms of these dose-volume parameters [46, 47].

Image-based brachytherapy has several benefits, which include knowing the tumor extent clearly, target-based prescription instead of a point-based prescription, evaluation of dose received by tumor and OARs, and optimizing the dose when necessary verifying the position of applicators and facility to use interstitial brachytherapy in combination with intracavitary brachytherapy.

Two CTVs are recommended for delineation in brachytherapy of the cervix. The first target is defined based on GTV at the time of diagnosis, called as intermediate risk CTV, to which a dose of 60 Gy is prescribed. The second target is defined based on GTV at the time of brachytherapy, known as High-Risk CTV. A dose of 80–90 Gy is prescribed to the second target. Dose-volume parameters for target volumes and OARs can be obtained from cumulative dose volume histogram (DVH) analysis in the 3D image-based treatment plan. The parameters for the target are the minimum dose delivered to 100% volume (D100) and 90% of the volume of interest (D90), respectively, and the volume enclosed by 100% of the prescribed dose. For OARs, parameters D2cc, D1cc and D0.1cc representing minimum dose to maximum irradiated tissue volumes of 2 cc, 1 cc and 0.1 cc are evaluated from DVH.

In three-dimensional ICRT planning, 3D images like CT and MRI are used. Patients undergo CT or MRI after the ICRT application. These images are then transferred to TPS for contouring and planning. CTV and OARs like bladder, rectum and bowel are delineated. After the delineation, applicator reconstruction and source loading are done. A dose of 7 Gy per fraction for three fractions is prescribed. The dose to target and OARs are calculated using the dose calculation algorithm in the TPS. A three-dimensional pear-shaped isodose distribution is obtained and displayed in the TPS (Figure 8). DVH parameters of the CTV, including D90, V100 and D100 and of the OARs, including D2cc, D1cc and D0.1cc, are evaluated from DVH. The plans are optimized for good target coverage and reduced OAR doses. These plans are then exported to the treatment console for treatment on a brachytherapy machine.

Figure 8.

Isodose distribution of an ICBT patient in (a) coronal view (b) sagittal view.

5. Toxicities of radiotherapy

Estimates of the risk of late complications of radical radiotherapy vary according to the grading system, duration of follow-up, method of calculation, treatment method, and prevalence of risk factors in the study population. However, most reports quote an overall risk of significant complications (requiring transfusion, hospitalization, or surgical intervention) of 5 to 15%. Complication rates may be higher in patients with very locally advanced disease partly because of tissue destruction caused by an infiltrative tumor.

Acute: During pelvic radiotherapy, most patients have mild fatigue and mild-to-moderate diarrhea that usually is controllable with antidiarrheal medications; some patients have mild bladder irritation, which may be symptomatic of a urinary tract infection. When extended fields are treated, patients may have nausea, gastric irritation, and depression of peripheral blood cell counts. Haematologic and gastrointestinal complications are significantly increased in patients receiving concurrent chemotherapy. Unless the ovaries have been transposed, all premenopausal patients who receive pelvic radiotherapy experience ovarian failure by the completion of treatment.

Perioperative complications of intracavitary brachytherapy include uterine perforation, fever and the usual risks of anesthesia.

Late: During the first 3 years after treatment, rectal complications (Radiation proctitis) are most common and include bleeding, stricture, ulceration and fistula. In the study by Eifel et al. [7], the risk of major rectosigmoid complications was 2.3% at 5 years. Major gastrointestinal complications were rare 3 years or more after treatment, but a constant low risk of urinary tract complications persisted for many years. The actuarial risk of developing a fistula of any type was 1.7% at 5 years. Small bowel obstruction is an infrequent complication of standard radiotherapy for patients without special risk factors.

Numerous psychological and physical factors can influence sexual function after pelvic radiation therapy. Most patients who received definitive radiation therapy for cervical cancer have some telangiectasia of the apical vagina. More significant vaginal shortening can occur, particularly in elderly, postmenopausal women and those with extensive tumors treated with a high radiation dose. Hypoestrogenism can enhance vaginal atrophy and dryness, contributing to dyspareunia. Intravaginal or systemic estrogen may reduce these symptoms. Vaginal dilatation and vaginal dilation may help prevent vaginal stenosis or improve quality of life.

6. Conclusion

Cervical carcinoma is the fourth most common malignancy in women worldwide, and it is most prevalent in Asia, Africa, and Central and South America. Radiotherapy plays a significant role in managing cervical cancer, with the standard mode of definitive treatment in locally advanced cervical carcinoma patients.

EBRT is part of the routine treatment of cervical carcinoma, targeting the draining lymph nodal groups and, in some cases, the para-aortic or inguinal group of lymph nodes. Intensity-Modulated Radiation Therapy (IMRT) is now recommended for EBRT due to its potential to reduce treatment-related toxicities and improve survival. Image-guided Radiotherapy (IGRT) is recommended along with IMRT/VMAT to limit PTV margins and ensure safe dose delivery. IMRT/VMAT can also safely deliver boost doses to pathological pelvic or para-aortic lymph nodes safely.

External beam radiotherapy along with brachytherapy is the standard treatment for cervical cancer with FIGO staging IIB-IIIB. The most common brachytherapy technique used in the treatment of cervical cancer is intracavitary brachytherapy, but in cases where intracavitary techniques are not feasible, interstitial brachytherapy is used. Image-based brachytherapy planning has emerged as a solution to the limitations of 2D image-based treatment planning. Image-based planning helps evaluate dose-volume parameters and their correlation with clinical results, improving tumor coverage and reducing the dose to organs at risk. Toxicities of radiotherapy vary according to the grading system, duration of follow-up, method of calculation, treatment method and prevalence of risk factors in the study population.