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Primary radiation therapy for cervical cancer


Medical editor Kolbein Sundfør MD
Gynecological Oncologist
Oslo University Hospital

General

Radiation therapy is the primary choice for patients with cervical cancer in stage Ib2-IVa and is combined with chemotherapy, if tolerated. Radiation therapy dosage or intensity should not be reduced to improve the tolerance of combined treatment. Chemotherapy should be reduced or stopped in such cases. Radiation therapy given together with chemotherapy is also appropriate for patients with inoperable cervical cancer stage Ib-IIa.

For stage IVb, radiation therapy may also be appropriate usually after chemotherapy.

For treatment planning, it is usually necessary to obtain information about the patient's general condition, psychosocial status, and other diseases. This may influence the patient's tolerance for treatment and how it is carried out. It is also important to confirm if other diseases significantly limit survival independent of the cervical cancer.  

Indications

  • Stage Ib2-IVa
  • Stage IVb

Goal

  • Cure the disease 

Definitions

Target volume

 

 

Target volume definitions from ICRU
(International Commission on Radiation Units and Measurements)
GTV (Gross tumor volume) Palpable or visible/identifiable area of malignant growth. 
CTV (Clinical target volume) Tissue volume which contains GTV and/or subclinical microscopic malignancy.
ITV (Internal Target Volume) Volume containing CTV and one inner margin taking into account inner movements and revisions of CTV.
PTV (Planning Target Volume) Geometric volume containing ITV and one Setup margin taking into account assumed variations for patient movements, variations in patient arrangement, and field modeling.

Preparation

Total local overview applies to the cervix and vagina/external genitals in addition to bordering tissue in case of possible spreading (or origin of the tumor if uncertain). The most common spreading routes are lymph node stations from the groin to diaphragm mainly retroperitoneal lymph nodes in the pelvis and abdomen and further as lung metastases. 

Imaging of the pelvis/abdomen should be by CT or MRI. These examinations also include the kidneys and urinary tracts (separate urography is not necessary). MRI is best for the pelvis, preferably performed at an MRI center. Images should be taken of the lungs from the front and side. If there is uncertainty, CT of the chest should be done. Good resolution is necessary to identify small changes. 

  • CT examination: CT must be taken with optimal image quality (no low-dose protocol). A multichannel CT must be used with thin sections (0.6 mm to maximally 3 mm). The CT should be reformatted into three dimensions. In general, the CT should be taken with intravenous contrast and exposure no later than the portovenous phase. Water should be used for contrast in the bowel.
  • MRI examination: For transversal, sagittal, or parasagittal series, the sectional thickness should be no more than 4 mm. Minimum T1 and T2-weighted transversal series through the entire pelvis, simultaneous sagittal series. 
  • To exclude/confirm lung metastases, a regular lung X-ray is normally adequate. However, with a high risk for lung or mediastinal metastases, such as in retroperitoneal metastases or very large tumors, a thoracic CT should be taken even if a regular X-ray is found negative (same requirement for sectional density).

Preparing the patient for external radiation therapy

CT dosage planning is done on a simulator at the radiation therapy unit. It is very important the patient is well medicated for pain and is able to lie still on her back for 20-30 minutes. If necessary, 1-2 g of paracetamol can be given as premedication. An extra dose of opiates may also be necessary. The patient will lie on a flat examination table with only a thin mattress. The patient will be given a standard pillow under her knees and one under her head. This positioning must be identical to the position used for the treatment apparatus. 

Intravenous contrast is used routinely. Patients taking metformin-type drugs such as metformin or glucophage must not take these at least two days before dosage planning.  

Planning of the radiation field (tracing, determination of radiation field, necessary adjustments, checks, and documentation for the simulator) takes 10-12 days under normal working conditions. See CT dosage plan 

Radiation therapy normally starts around 10-12 days after CT planning.

Preparing the patient for brachytherapy

  • Fasting regimen
  • Premedication 1 hour before planned treatment
  • Patients taking pain medication regularly should take it as normal. An additional dose may be given with the premedication.
  • Enema before brachytherapy is given only to patients with constipation problems and not otherwise to avoid unnecessary bowel irritation after external radiation to the pelvis. 

Implementation

Radiation therapy is given daily five days per week. The total treatment period is seven weeks. Brachytherapy is given 1-2 times per week. This starts normally after 30 Gy of external radiation therapy after the tumor is evaluated by examination under general anesthesia, CT or MRI.

External radiation therapy

Twenty-five external treatments are given to the pelvic area. Four to six fields are confined.  

Brachytherapy

Five to six brachytherapy treatments are given toward the cervix usually 1-2 times per week from the fourth treatment week. After external radiation therapy is completed, the remaining brachytherapy is given 2-3 times per week. 

  • The entire procedure is done on the CT table at the brachytherapy unit.
  • The gynecological examination, probing, and dilatation of the cervical canal is performed under general anesthesia. Depending on the tumor changes, this may be technically challenging.
  • After the cervical canal is dilated, the dimension and type of treatment applicators are chosen, inserted and fixed.
  • The patient is then positioned for CT imaging and treatment.
  • The CT examination determines the positioning and is the basis for dosage planning. We avoid transport since everything is done on the same CT machine. The patient lies on the CT table until the subsequent procedures and treatment are completed.
  • The applicators are reconstructed on the CT images and a standard dosage distribution is applied.
  • The plan is approved by a doctor who makes adjustments according to the tumor and risk organs such as the bladder and rectum, and finally determines if there is adequate coverage.
  • The plan is transferred to the control unit of the treatment apparatus. In the meantime, this is connected to the inserted applicators.   
  • The treatment is given for 5-10 minutes.
  • The equipment is taken out and the patient is returned to the bed.
  • The total time for the entire procedure is 1.5 to 2 hours.
  • If MRI is taken as part of the process, the patient is transported with the equipment inserted.

In some cases, it is necessary to give 7–9 extra treatments towards smaller parts of the total fields. This is usually planned together with the main treatment plan. Sometimes, however, this is not decided until the end of the main treatment plan and after the first brachytherapy fractions are completed and evaluated.

Chemotherapy

Cisplatin is given on day 1 of the entire treatment period, usually for 6 weekly courses.

If the tumor is too large, a new evaluation is done later since the tumor may shrink during treatment.


Follow-up

Most side effects occurring during treatment are due to healthy organs included in the radiation field. This includes parts of the small and large intestine, bladder, upper vagina, lymph nodes, ovaries, some pelvic bone, and uterus.

Radiation therapy to the pelvis can lead to:

  • Diarrhea and abdominal pain.
  • Nausea, which may be enhanced by chemotherapy.
  • Fatigue
  • Irritation of bladder mucosa. This leads to problems resembling urinary tract infections including frequent urination, burning, pain, and light bleeding. 
  • Bone marrow changes
  • The vaginal mucosa may be dry/sore and stenoses may occur in the vagina.
  • Since the ovaries are situated in the field of radiation, the ovaries will stop producing hormones and the patient will start menopause. 
  • Skin reactions are rare. If this should occur, it is usually in the gluteal fold. 

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