Endometrium

All Stages Advanced disease or if symptoms warrant INTERNATIONAL SOCIETY OF GYNECOLOGIC PATHOLOGISTS CLASSIFICATION OF ENDOMETRIAL CARCINOMAS GYNECOLOGIC ONCOLOGY GROUP CLASSIFICATION FOR UTERINE SARCOMAS https://uwlmedicaldosimetry2012.wikispaces.com/Cervix || Grade 1 is a low grade cancer which is a slower growing cancer and is less likely to spread (Poorly differentiated) Grade 2 is a moderate grade cancer which is more likely to grow and spread than a grade 1 cancer (Moderately differentiated) Grade 3 is a high grade cancer which will grow quickly and is likely to spread (Well differentiated) || Inoperable Stage I Endometrial Carcinoma 3 Stage II Endometrial Carcinoma 3 Stage III Endometrial Carcinoma 3 Stage IV Endometrial Carcinoma 3 Radioactive Phosphorus 3 Chemotherapy 3 Recurrent Endometrial Carcinoma 3 Radiation Therapy Techniques 3 <span style="color: #0000ff; font-family: Arial,Helvetica,sans-serif;">BLADDER--65 Gy <span style="color: #0000ff; font-family: Arial,Helvetica,sans-serif;">RECTUM--60 Gy <span style="color: #0000ff; font-family: Arial,Helvetica,sans-serif;">COLON---45 Gy <span style="color: #0000ff; font-family: Arial,Helvetica,sans-serif;">FEMORAL HEAD--52 Gy <span style="color: #0000ff; font-family: Arial,Helvetica,sans-serif;">SMALL INTESTINE--40Gy ||  ||   ||
 * **Epidemiolgy:** || Endometrical cancer is the most common gynecological malignancy and the fourth most common cancer in women. The United States has the highest incident rate in the world, with incident rate about 25 cases per 100,000 women.Endometrial cancer is typically a cancer of postmenopausal women (about 75% of all cases) between the ages of 55 to 85 years old. Less than 5% of the patients are younger than 40 years old. The incidence of endometrial cancer is decreasing, most likely due to improved diagnostic procedures and general awareness.5 ||
 * **Etiology:** || The cause of endometrial cancers is related to exposure of the endometrium to unopposed estrogens. Other risk factors include:6
 * early menarche
 * late menopause
 * obesity
 * nulliparity
 * infertility
 * hypertension and diabetes
 * there is an increased risk associated with family history of the disease, especially in women younger than 50 years old
 * the use of tamoxifen for the prevention and treatment of breast cancer ||
 * **Signs & Symptoms:** || * The most common presenting symptom of endometrial cancer is vaginal bleeding, which is reported by 70% to 80% of patients.
 * Back pain and pressure symptoms caused by the enlarged uterus on bowel and bladder may occur.
 * Physical finding are usually minimal; blood in the vagina emanating from the cervical os is the most common finding.5 ||
 * **Diagnostic Procedures:** || ** Diagnostic Work-up for Endometrial Cancers ** 7
 * History
 * Physical examination including pelvic examination
 * Endometrial biopsy or aspiration curettage
 * Fractional dialation and curettage (if biopsy or aspiration does not reveal cancer)
 * Chest radiograph
 * Cervical biopsy
 * Complete blood cell count, urinalysis, blood chemistry
 * Cystoscopy
 * Sigmoidoscopy
 * Computed tomography scan, magnetic resonance imaging, or ultrasonography
 * Intravenous pyelogram
 * Barium enema ||
 * **Histology:** |||| ** Classifications of Endometrial Cancer8 **
 * Endometrioid adenocarcinoma
 * Villoglandular
 * Secretory
 * Ciliated cell
 * Adenocarcinoma with squamous differentiation
 * Mucinous carcinoma
 * Serous carcinoma
 * Clear cell carcinoma
 * Squamous carcinoma
 * Undifferentiated carcinoma
 * Mixed type
 * Miscellaneous carcinoma
 * Metastatic carcinoma
 * Mesenchymal
 * Leiomyosarcoma
 * Endometrial stromal sarcoma
 * Low grade (endolymphatic stromal myosis)
 * High grade (undifferentiated sarcoma)
 * Mixed differentiated sarcomas
 * Other
 * Mixed epithelial-stromal
 * Adenosarcoma
 * Carcinosarcoma (mixed malignant müllerian tumor)
 * Without heterologous elements
 * With heterologous elements ||
 * **Lymph node drainage:** || The endometrium proper has few lymphatics. However, once a tumor penetrates the myometrium, and especially when it reaches the lymphatic-rich subserosa, spread via lymphatic embolization is common. Refer to uterine cervix lymph node drainage. 9
 * **Metastatic spread:** || For endometrial cancer, the pattern of spread varies with grading. Higher-grade tumors tend to limit spread to the endometrial surface, lower grade tumors myometrial invasion occurs much more frequently. Myometrial invasion usually accompanies lymph node involvement and distant spread. Most common distant metastasis involves the lungs, liver, bones, brain and vagina.10 ||
 * **Grading:** || Standard grading is applied for endometrial cancer:
 * **Staging:** || [[image:uwlmedicaldosimetry2012/endo staging.JPG]] ||
 * **Radiation side effects:** || * <span style="color: #0000ff; font-family: Arial,Helvetica,sans-serif;">Several radiosensitive organs are located around this treatment area, and ways to decrease side effects to these critical structures need to be taken. <span style="color: #0000ff; font-family: Arial,Helvetica,sans-serif; vertical-align: super;">1
 * <span style="color: #0000ff; font-family: Arial,Helvetica,sans-serif;">One of the most severe complications is rectovaginal or vesicovaginal fistulas <span style="color: #0000ff; font-family: Arial,Helvetica,sans-serif; vertical-align: super;">1
 * <span style="color: #0000ff; font-family: Arial,Helvetica,sans-serif;">Caused when the vaginal wall is destroyed leaving an opening between either the bladder and vagina or the rectum and bladder
 * <span style="color: #0000ff; font-family: Arial,Helvetica,sans-serif;">Other side effects include: <span style="color: #0000ff; font-family: Arial,Helvetica,sans-serif; vertical-align: super;">1
 * <span style="color: #0000ff; font-family: Arial,Helvetica,sans-serif;">Proctitis, cystitis, urethral stricture, rectal ulcer, sigmoid stricture, small bowel obstruction and pelvic abscess.
 * Late complications include:
 * Chronic cystitis( 6 mths post tx at doses above 50-60Gy)
 * Contracture/ hemorrhagic cystitis( dose above 65Gy)
 * Bowel obstruction ( at doses above 45Gy). ||
 * **Prognosis:** || * <span style="color: #0000ff; font-family: Arial,Helvetica,sans-serif;">Age at diagnosis plays an important role in the prognosis. Older patients have a higher chance of myometrial involvement, advanced stage and a lower 5 year survival. <span style="color: #0000ff; font-family: Arial,Helvetica,sans-serif; vertical-align: super;">2
 * <span style="color: #0000ff; font-family: Arial,Helvetica,sans-serif;">Stage is the most significant factor effecting prognosis and survival <span style="color: #0000ff; font-family: Arial,Helvetica,sans-serif; vertical-align: super;">2
 * <span style="color: #0000ff; font-family: Arial,Helvetica,sans-serif;">Depth of invasion has been linked to increased risk of relapse <span style="color: #0000ff; font-family: Arial,Helvetica,sans-serif; vertical-align: super;">2
 * <span style="color: #0000ff; font-family: Arial,Helvetica,sans-serif;">Lymphovascular invasion is a major prognostic factor that significantly and independantly increases the risk of relapse <span style="color: #0000ff; font-family: Arial,Helvetica,sans-serif; vertical-align: super;">2 ||
 * **Treatments:** || <span style="color: #0000ff; font-family: Arial,Helvetica,sans-serif;">Operable Stage I Endometrial Carcinoma <span style="color: #0000ff; font-family: Arial,Helvetica,sans-serif; vertical-align: super;">3
 * <span style="color: #0000ff; font-family: Arial,Helvetica,sans-serif;">Total abdominal hysterectomy and bilateral salpingo-oophorectomy is the basic treatment for all patients with stage I endometrial carcinoma.
 * <span style="color: #0000ff; font-family: Arial,Helvetica,sans-serif;">In all but grade I lesions, it is recommended that pelvic and periaortic lymph node sampling be performed at the time of surgical exploration. The incidence of nodal involvement in stage I patients with grade I histology is too low to make routine sampling of lymph nodes worthwhile.
 * <span style="color: #0000ff; font-family: Arial,Helvetica,sans-serif;">Peritoneal washings are recommended for all patients at time of surgery.
 * <span style="color: #0000ff; font-family: Arial,Helvetica,sans-serif;">In the US, surgery is done on most patients with stage I disease, regardless of tumor grade, to adequately assess the extent of diesease and allow radiation therapy to be tailored to the pathologic findings.
 * <span style="color: #0000ff; font-family: Arial,Helvetica,sans-serif;">In stage I patients with grade I tumors and less than 50% myometrial invasion, no further therapy is recommended because the prognosis is good.
 * <span style="color: #0000ff; font-family: Arial,Helvetica,sans-serif;">In patients with stage I, grade II disease and less than 50% but more than 25% myometrial invasion, it is debatable whether vaginal cuff radiation is indicated. Although this adjuvant therapy is the subject of debate, it may be justifiable in patients with stage I, grade III disease who have from 25% to less than 50% myometrial invasion.
 * <span style="color: #0000ff; font-family: Arial,Helvetica,sans-serif;">Post-op radiation is recommended in patients with stage I, grade I or II disease with more than 50% myometrial involvement, and in patients with grade III disease regardless of depth of myometrial invovlement.
 * <span style="color: #0000ff; font-family: Arial,Helvetica,sans-serif;">Vaginal cuff radiation is delivered with colpostats or vaginal cylinders. The dose with low-dose-rate (LDR) brachytherapy is 60-70 Gy to the vaginal mucosa in one or two insertions. With high-dose-rate (HDR) brachytherapy, the prescription is 6-7 Gy per fraction at 0.5-cm depth; 3 fractions given 1-2 weeks apart.
 * <span style="color: #0000ff; font-family: Arial,Helvetica,sans-serif;">High-risk patients are sometime treated with a combination of external-beam radiation and vaginal cuff insertion.
 * <span style="color: #0000ff; font-family: Arial,Helvetica,sans-serif;">Two brachytherapy insertions for 7,000- 8,000 mgRaEq-h (LDR) and external-beam radiation to the pelvis to a total dose of 50.4 Gy with a midline block at 20Gy is recommended for patients who are medically inoperable.
 * <span style="color: #0000ff; font-family: Arial,Helvetica,sans-serif;">Patients with stage II endometrial carcinoma are subdivided into those with endocervical glandular involvement and those with cervical stromal invasion.
 * <span style="color: #0000ff; font-family: Arial,Helvetica,sans-serif;">The gynecologic oncologic community favors surgery followed by post-op radiation, based on histologic findings.
 * <span style="color: #0000ff; font-family: Arial,Helvetica,sans-serif;">The incidence of pelvic lymph node involvement varies from 20%- 50% in patients with stromal involvement. This necessitates adequate treatment of nodal areas and parametrial tissues with external pelvic radiation.
 * <span style="color: #0000ff; font-family: Arial,Helvetica,sans-serif;">Survival for patients with stage II disease ranges from 50%- 85%. Patients with endocervical glandular involvement only (stage IIA) have a much better 5-year survival rate than those with cervical stromal invasion.
 * <span style="color: #0000ff; font-family: Arial,Helvetica,sans-serif;">Treatments for stage III disease must be individualized.
 * <span style="color: #0000ff; font-family: Arial,Helvetica,sans-serif;">In the US the trend has been to do surgery first on patients without extensive parametrial or vaginal extension to assess the extent of the disease and debulk the tumor.
 * <span style="color: #0000ff; font-family: Arial,Helvetica,sans-serif;">All stage III patients are candidates for post-op radiation after surgical staging and debulking of the tumor.
 * <span style="color: #0000ff; font-family: Arial,Helvetica,sans-serif;">Radiation fields are defined by the histologic extent of the tumor.
 * <span style="color: #0000ff; font-family: Arial,Helvetica,sans-serif;">Patients with periaortic nodal involvment should be treated with extended-field radiation encompassing the periaortic lymph nodes. The recommended dose for the periaortic lymph nodes is 45 Gy, and the pelvic dose to 50.4 Gy.
 * <span style="color: #0000ff; font-family: Arial,Helvetica,sans-serif;">For inoperable patients, whole-pelvis radiation (20-40 Gy) and additional boost to the lateral pelvic wall to 50-60 Gy after placement of a midline block (depending on clinical evidence of parametrial invasion), combined with 2 LDR intracavitary implantations for a total of 5,000- 8,000mgRaEq-h, is the treatment of choice.
 * <span style="color: #0000ff; font-family: Arial,Helvetica,sans-serif;">Medically inoperable patients with bladder or rectal wall involvement without pelvic wall fixation may be considered for pelvic exenteration.
 * <span style="color: #0000ff; font-family: Arial,Helvetica,sans-serif;">Patients with stage IVB disease may be treated with whole-pelvic radiation for control of local symptoms of bleeding, discharge, and pelvic pain.
 * <span style="color: #0000ff; font-family: Arial,Helvetica,sans-serif;">Intraperitoneal 32P is effective in decreasing recurrences in selected patients with subclinical intraperitoneal disease. The usual dose is 15 mCi.
 * <span style="color: #0000ff; font-family: Arial,Helvetica,sans-serif;">It is strongly recommended not to combine this treatment with external-beam radiation to the pelvis because of excessive bowel toxicity.
 * <span style="color: #0000ff; font-family: Arial,Helvetica,sans-serif;">Doxorubicin (Adriamycin) is the principal theraputic agent used to treat patients with metastatic endometrial cancer.
 * <span style="color: #0000ff; font-family: Arial,Helvetica,sans-serif;">Optimal treatment for recurrent endometrial cancer depends on the size of the recurrent tumor, spread of tumor beyond the confines of the true pelvis, and type of therapy delivered after initial diagnosis.
 * <span style="color: #0000ff; font-family: Arial,Helvetica,sans-serif;">It is recommended that patients with recurrent cancer in the pelvis who have not received previous radiation, to administer external-beam radiation to the whole pelvis (45-50 Gy in 5-6 weeks).
 * <span style="color: #0000ff; font-family: Arial,Helvetica,sans-serif;">An additional boost of 10-15 Gy to the tumor bulk can be delivered with external-beam radiation when the tumor involves the central pelvis or the pelvic side wall.
 * <span style="color: #0000ff; font-family: Arial,Helvetica,sans-serif;">Vaginal recurrences can receive boost radiation with intracavitary or interstitial radiation therapy to bring the total tumor dose to 80 Gy.
 * <span style="color: #0000ff; font-family: Arial,Helvetica,sans-serif;">Patients with disseminated tumors are treated with progestational agents, which may be given alone or combined with chemotherapy, depending on the status of estrogen or progesterone receptors.
 * <span style="color: #0000ff; font-family: Arial,Helvetica,sans-serif;">Radiation therapy in indicated for palliation.
 * <span style="color: #0000ff; font-family: Arial,Helvetica,sans-serif;">The external-beam field should extend superiorly to cover the common iliac lymph nodes and inferiorly to encompass the upper half of the vagina.
 * <span style="color: #0000ff; font-family: Arial,Helvetica,sans-serif;">The lateral border of the treatment field should extend 1.5- 2-cm beyond the border of the bony pelvis to include the pelvic lymph nodes.
 * <span style="color: #0000ff; font-family: Arial,Helvetica,sans-serif;">Treatment can be delivered using a 4-field box technique to provide a homogeneous dose distribution.
 * <span style="color: #0000ff; font-family: Arial,Helvetica,sans-serif;">If external-beam therapy alone is to be used post-op, a dose of 45-50 Gy is indicated.
 * <span style="color: #0000ff; font-family: Arial,Helvetica,sans-serif;">If external-beam radiation is combined with brachytherapy, a dose of 20-30 Gy, with an additional prametrial boost (with midline block) to deliver 50 Gy to the pelvic lymph nodes, is used.
 * <span style="color: #0000ff; font-family: Arial,Helvetica,sans-serif;">For pre-op intracavitary insertions, the vaginal wall should be irradiated.
 * <span style="color: #0000ff; font-family: Arial,Helvetica,sans-serif;">If there is tumor extension into the vagina, the entire length of the organ should be treated iwth a cylinder, Delclos applicator, or Syed interstitial implant because of the propensity of advanced endometrial tumors to metastasize to this site.
 * <span style="color: #0000ff; font-family: Arial,Helvetica,sans-serif;">In patients with recurrent tumors, the choice of intracavitary device depends on tumor bulk and location. The entire vagina should be treated. The uninvolved mucosa should receive doses of 50-60 Gy, depending on the external-beam dose to the whole pelvis. A total dose of approximately 75-80 Gy should be used.
 * <span style="color: #0000ff; font-family: Arial,Helvetica,sans-serif;">Medically inoperable patients can be treated with radiation alone. Two intracavitary insertions to deliver 60 Gy to the vaginal surface are combined with external-beam radiation with an additional 20-40 Gy to the whole pelvis and subsequent boosting of the lateral pelvic wall to ta total dose of 50 Gy. A midline pelvic shield protects the bladder and bowel. Additional boost radiation is indicated if there is residual tumor ||
 * **TD 5/5:** || <span style="color: #0000ff; font-family: Arial,Helvetica,sans-serif;">TD 5/5 <span style="color: #0000ff; font-family: Arial,Helvetica,sans-serif; vertical-align: super;">4
 * **References:** || # <span style="color: #0000ff; font-family: Arial,Helvetica,sans-serif;">Bentel GC. //Radiation Therapy Planning//. 2nd ed. The McGraw-Hill Companies; 1996: 445-450, 458.
 * 1) <span style="color: #0000ff; font-family: Arial,Helvetica,sans-serif;">Uschold GM, Anderson JE. //Principles and Practice of Radiation Therapy//. 3rd ed. Mosby, Inc; 2010: 815-818.
 * 2) <span style="color: #0000ff; font-family: Arial,Helvetica,sans-serif;">Chao KC, Perez CA, Brady LW. //Radiation Oncology Management Decisions//. 3rd ed. Philadelphia, PA; Lippincott Williams & Wilkins. 2011: 579-588.
 * 3) <span style="color: #0000ff; font-family: Arial,Helvetica,sans-serif;">Radiation Oncology/Toxicity/Emami. Wikibooks. Available at: []. Accessed: June 2, 2012.
 * 4) Chao KC, Perez CA, Brady LW. //Radiation Oncology Management Decisions//. 3rd ed. Philadelphia, PA; Lippincott Williams & Wilkins. 2011: 579-588.
 * 5) Gunderson LL, Tepper JE. //Clinical Radiation Oncology//. 2nd ed. Philadelphia, PA: Elsevier, Churchill & Livingstone. 2007: 1360-1363.
 * 6) Perez CA, Brady LA, Halpern EC, Schmidt-Ullrich RK. //Principles and Practice of Radiation Oncology//. 4th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2004
 * 7) Abeloff MD, Armitage JO, Niederhuber JE, Kastan MB, McKenna WG. //Abeloff's Clinical Oncology//. 4th ed. Philadelphia, PA: Churchill Livingstone; 2008.
 * 8) Hoppe RT, Phillips TL, Mack III M. //Leibel and Phillips Textbook of Radiation Oncology//. 3rd ed. Philadelphia Pa: Elsevier Saunders; 2010
 * 9) National Cancer Institute. General Information About Endometrial Cancer. []. Accessed. June 23 2012 ||
 * 1) National Cancer Institute. General Information About Endometrial Cancer. []. Accessed. June 23 2012 ||

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