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Adjuvant postoperative radiation treatment for uterine cancer


Medical editor Kolbein Sundfør MD
Gynecological Oncologist
Oslo University Hospital

General

Adjuvant radiation treatment is used for patients at high risk for pelvic tumor recurrence after an operation. 

Stage I

Endometrioid tumors in stage Ia-b grade 1–2 are categorized as low risk. It is not recommended to give adjuvant treatment to this patient group. 

Endometrioid tumors in stage Ic grade 1–2 as well as stage Ia-b grade 3 are considered moderate risk. The frequency of recurrence is about 10%. Recurrences are most frequently localized to the vagina or pelvis and can be treated with radiation therapy achieving good results (15). An effect on survival has not be found for adjuvant radiation therapy of these two patient groups (16). We do not recommend giving adjuvant treatment to this patient group.

Endometrioid tumors in stage Ic grade 3 are considered high risk having a risk for recurrence of about 25%. Recurrences are partly localized to the pelvis and partly outside the pelvis. Traditionally, adjuvant radiation therapy was given to this patient group, which reduced the frequency of local recurrence. It is still not clear whether this extends survival time (17). More recent studies have shown improved survival time with adjuvant chemotherapy instead of radiation treatment. For tumors remaining after treatment, consolidated radiation treatment may be considered. 

Serous papillary as well as clear cell tumors have a high risk for recurrence in both stage Ia, Ib and Ic. Radiation treatment to the pelvis reduces the risk for pelvic recurrences (18). Recurrences are, however, often localized outside the pelvis (18). Today adjuvant chemotherapy is given to this patient group instead of radiation therapy. Adjuvant treatment with progestagens has no documented effect in this group. 

Stage II

  • Stage IIa: Classified as stage I
  • Stage IIb: If a normal hysterectomy is performed, it is recommended to give external radiation therapy to a reduced pelvic field.

Stage III

  • Stage IIIa: The prognostic significance is debated for a positive cytology. There is no documentation on the effect of adjuvant treatment. 
  • If there are metastases to the adnexa or infiltration of the uterine wall, there is an increased risk for recurrence as much for tumor localized to the pelvis as outside. Traditionally, external radiation therapy to the pelvis has been given to these patients even though there is no documented effect on survival. Today, postoperative chemotherapy is given which is assumed to improve survival.  
  • Stage IIIb: Vaginal metastases are treated often with radition therapy combined with external and brachytherapy.
  • Stage IIIc: Patients with metastases to paraaortal lymph nodes are given chemotherapy if all tumor is removed, but not radiation treatment.

Indication

  • High risk for pelvic recurrence after the operation.

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/demonstrative 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

MRI and CT examinations covering the pelvis and lymph node stations retroperitoneally to the diaphragm should be present before treatment is started. 

  • 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 medium 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 through the entire pelvis, simultaneous sagittal series.
  • A lung X-ray from the front and side should be taken before the operation. If the images are over two months old, new images are taken for large tumors or multiple metastases. Suspect or ambiguous findings are examined with lung CT.  

The radiation field covers the area of lymphogenic spreading in the pelvis. That is, from the floor of the pelvis to the inguinal ligament to 1 cm under vertebra L4-L5 where the field limit is in the vertebra. When a short distance to the resection margin is the only indication, the upper field limit can be made lower.  

Preparation for the patient

  • The treating radiologist will assess the status of the tumor locally. Marking is done, for example, of the top of the vagina. This should be done simultaneously with the referral, and at the latest before the CT dosage planning. 
  • CT dosage planning is done on a simulator. It is very important the patient is well medicated for pain and is able to lie still on her back during the time required. If necessary, premedication can be given to calm the patient. 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. 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 .

Radiation therapy will start around 10-12 days after the CT dosage plan.

 


Implementation

  • To the risk area, 45–50 Gy is given.
  • Normally, 27 (25) external treatments are given of 1.8-2 Gy with 4 radiation fields to the pelvic area with boost to the tumor.  
  • For some, it may be necessary to give individualized supplementary treatment.

Radiation therapy is given every day, 5 days per week. The total treatment time is about 6 weeks.


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 worsened 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. Hormone substitution is not given for endometrial cancer.
  • Skin reactions are rare. If this should occur, it is usually in the gluteal fold. 

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