Endometrium

-Hypertension and diabetes have been associated with endometrial cancers but it is not clear if they are independant risk factors or associated with obesity. 2 -The use of tamoxifen for the prevention and treatment of breast cancer statistically increases the risk of endometrial cancer. 2  -Patients with endometrial biopsies confirming hyperplasia with atypia have a 30 to 40% risk of later developing endometrial cancer. 2 -There is an increased risk associated with family history of the disease, especially in women younger than 50 years old. Only 1% of all endometrial cancers have been attributed to familial and genetic factors. 2  -"Women with mutations on the MHL1 and MLH2 genes are at an increased risk for developing endometrial cancer. 2  " -"Women with Lynch syndrome II have a 20% risk of developing endometrial cancer before age 50, which increases to 60% by age 60. 2 " || -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. 1 || - The papanicolaou smear detects only approximately 40% of endometrial tumors. - Endometrial biopsy or aspiration curettage is indicated in postmenopausal women with vaginal bleeding or perimenopausal women with menstrual abnormalities, and obviates in most cases the need for dilation and curettage. - Fractional dilation and curettage and cervical biopsy are indicated when there is a high degree of suspicion of cancer and diagnosis cannot be made by endometrial biopsy or aspiration curettage. -Diagnostic studies routinely used in the clinical staging of patients with endometrial cancer vary with stage. - Computed tomography of the pelvis and abdomen is recommended for all patients with high-grade tumors or with stage II or higher disease to detect possible nodal or extrauterine spread of cancer. - MRI is not helpful in detecting nodal or peritoneal spread; however, it is useful in demonstrating the depth of myometrial invasion, with an accuracy of approximately 80%.
 * Epidemiology: || Endometrical cancer is the most common gynecological malignany and the fourth most common cancer in women. The incident rate is about 25 cases per 100,000 women in the United States. The United states has the highest incident rate in the world. Europe has an incident rate of approximately 15 to 20 cases per 100,000 women. Endometrial cancer is typically a cancer of postmenopausal women ( about 75% of all cases 1 ) between the age of 55 to 85 years old. Less than 5% of the patients are younger than 40 years old. <span style="color: #ff00ff; font-family: 'Times New Roman',Times,serif; vertical-align: super;">2 ||
 * Etiology: || <span style="color: #ff00ff; font-family: 'Times New Roman',Times,serif;">-The cause of endometrial cancers is related to exposure of the endometrium to unopposed estrogens. Early menarche, late menopause, obesity, nulliparity, infertility, and estrogen inducing ovarian tumors are associated with the development of endometrial cancers. <span style="color: #ff00ff; font-family: 'Times New Roman',Times,serif; vertical-align: super;">2
 * Signs & Symptoms: || - The most common presenting symptom is vaginal bleeding, which is reported by 70% to 80% of patients.
 * Diagnostic Procedures: || - No satisfactory screening method is available for detecting endometrial carcinoma in symptomatic patients.


 * __Diagnostic workup for endometrial cancer__**

Histroy Physical examination, including pelvic examination Endometrial biopsy or aspiration curettage Fractional dilation and curettage (if biopsy or aspiration does not reveal cancer) Chest radiograph Cervical biopsy Urinary imaging study in all patients before surgery (IVP, ultrasound, CT) Complete blood cell count, urinalysis, blood chemistry
 * __ALL STAGES__**

Cystoscopy Sigmoidoscopy CT scan or MRI IVP Barium enema 1 ||
 * __ADVANCED DISEASE OR IF SYSTEMS WARRANT__**
 * Histology: || <span style="color: #008000; font-family: 'Times New Roman',Times,serif; font-size: 110%;">Endometrioid adenocarinomas are the most common form and make up about 75% to 80% of all cases. This type can be further broken down in to papillary, secretory, ciliated, and adenocarcinoma with squamous differentiation. Secretory carcinomas account for only about 2% of endometrial carcinomas and are most commonly well differentiated and have a good clinical outcome. Ciliated carcinomas are uncommon as well and also have a good prognosis. They are often associated with prior estrogen use. "The most aggressive cancers arising from the endometrial lining include serous carcinomas, clear cell carcinomas, and pure squamous carcinomas. Serous and clear cell tumors tend to occur in older women. Serous carcinomas represent less than 10% of endometrial carcinomas, and clear cell tumors account for less than 4%. Serous tumors are frequently associated with peritoneal spread at the time of initial diagnosis." <span style="color: #008000; font-family: 'Times New Roman',Times,serif; font-size: 88%; vertical-align: super;">5

<span style="color: #008000; font-family: 'Times New Roman',Times,serif; font-size: 110%;">Figure 2. Tumor classification for endometrium proposed by the International Society of Gynecologic Pathologists. <span style="color: #008000; font-family: 'Times New Roman',Times,serif; font-size: 88%; vertical-align: super;">5 || Figure 3. Lymph node drainage of the pelvis. <span style="color: #008000; font-family: 'Times New Roman',Times,serif; font-size: 88%; vertical-align: super;">4 <span style="color: #008000; font-family: 'Times New Roman',Times,serif; font-size: 110%;">
 * Lymph Node Drainage: || <span style="color: #008000; font-family: 'Times New Roman',Times,serif; font-size: 110%;">[[image:diagram_of_pelvic_nodes_001.jpg]]

"Lymphatic drainage includes the inguinal lymph nodes (external and internal), pelvic nodes (the internal iliac chain, which originates approximately with the obturator node, and external iliac chain), and peri-aortic nodes. The deep inguinals drain into the external iliac chain, and the internal and external iliac chains join and then drain into the peri-aortics." <span style="color: #008000; font-family: 'Times New Roman',Times,serif; font-size: 80%; vertical-align: super;">4 || <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">Table provided by American Cancer Society. <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 88%; vertical-align: super;">7 ||
 * Metastatic Spread: || <span style="color: #008000; font-family: 'Times New Roman',Times,serif; font-size: 110%;">Endometrial tumors commonly spready into contiguous areas. Direct extension may include the cervix, vagina, parametrial tissue, bladder, or rectum. The ovaries may become involved by transtubal seeding or vascular metastasis. Peritoneal seeding is more common with endometrial cancer than with cervical cancer because endometral tumors can penetrate the uterine wall or seed transtubally. This is most common with papillary serous or clear cell histologies. "Uterine sarcomas metastasize frequently by hematogenous routes; metastases to the lung develop in 50% to 80% at some time during the clinical course. The incidence of pelvic lympn node involvement is also high, with estimates ranging from 25% to 50% at time of presentation." <span style="color: #008000; font-family: 'Times New Roman',Times,serif; font-size: 88%; vertical-align: super;">5 <span style="color: #008000; font-family: 'Times New Roman',Times,serif; font-size: 110%;"> ||
 * Grading: || [[image:endo_grading.jpg width="448" height="579"]]
 * Staging: || <span style="color: #0000ff; font-family: 'Times New Roman',Times,serif;">The International Federation of Gynecology and Obstetrics staging system is used for carcinoma of endometrial cancer see figure 1.1 . FIGO staging system is based on surgical-pathologic findings ( see figure 1.2 below). 3

<span style="color: #0000ff; font-family: 'Times New Roman',Times,serif; vertical-align: super;"> Figure 1.1 Staging of carcinoma of endometrial cancer 3

Figure 1.2 Anatomic staging for endometrial carcinoma 3 <span style="color: #0000ff; font-family: 'Times New Roman',Times,serif; font-size: 80%; vertical-align: super;"> || -The age at diagnosis is an important factor. Older patients have a higher chance of myometrial involvement, advance stage and a lower 5 year survival. <span style="color: #ff00ff; font-family: 'Times New Roman',Times,serif; vertical-align: super;">1 <span style="color: #ff00ff; font-family: 'Times New Roman',Times,serif;">-"The most significant prognostic factor is clinical or pathologic stage. <span style="color: #ff00ff; font-family: 'Times New Roman',Times,serif; vertical-align: super;">1 <span style="color: #ff00ff; font-family: 'Times New Roman',Times,serif;">" -In most studies, depth of myometrial invasion had a less strong prognostic value than tumor grade. <span style="color: #ff00ff; font-family: 'Times New Roman',Times,serif; vertical-align: super;">2 <span style="color: #ff00ff; font-family: 'Times New Roman',Times,serif;">-Depth of invasion into the outer third of the myometrial wall has been associated with an increased risk of relapse. <span style="color: #ff00ff; font-family: 'Times New Roman',Times,serif; vertical-align: super;">2 <span style="color: #ff00ff; font-family: 'Times New Roman',Times,serif;">-Lymphovascular invasion is a major prognostic factor that significantly and independantly increases the risk of relapse ( especially distant relapse). <span style="color: #ff00ff; font-family: 'Times New Roman',Times,serif; vertical-align: super;">2 ||
 * Radiation Side Effects: || <span style="color: #0000ff; font-family: 'Times New Roman',Times,serif;">Diarrhea, bleeding, urgency and pain are acute symptoms that can occur at 30 -40 Gy. A dose of 4-5 Gy to the ovary, produces a permanent cessation of menses in most young women and 100% of women older than 50. <span style="color: #0000ff; font-family: 'Times New Roman',Times,serif; vertical-align: super;">4 <span style="color: #0000ff; font-family: 'Times New Roman',Times,serif;"> If the whole bladder is treated , acute cystitis can occur at doses of 30Gy. Acute erythema and desquamation can occur in the vulva and perineum areas at doses above 40 Gy. The uterus and cervix can tolerate high doses of radiation therapy . <span style="color: #0000ff; font-family: 'Times New Roman',Times,serif;">Brachytherapy can deliver extremely high doses without necrosis .<span style="color: #0000ff; font-family: 'Times New Roman',Times,serif;"> Late complications include: chronic cystitis( 6 mths post tx at doses above 50-60Gy), Contracture/ hemorrhagic cystitis( dose above 65Gy), and bowel obstruction ( at doses above 45Gy). <span style="color: #0000ff; font-family: 'Times New Roman',Times,serif; vertical-align: super;"> 4 ||
 * Prognosis: || <span style="color: #ff00ff; font-family: 'Times New Roman',Times,serif;">-"Comprehensive retrospective analyses and prospective, randomized studies have established major prognostic factors for survival and relapse to be: Stage, Patient age, Histological cell type, Tumor grade, Depth of myometrial invasion, and prescence of lymphvascular space invasion. <span style="color: #ff00ff; font-family: 'Times New Roman',Times,serif; vertical-align: super;">2 <span style="color: #ff00ff; font-family: 'Times New Roman',Times,serif;">"
 * Treatments: || <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">Operable Stage I Endometrial Carcinoma


 * <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">Total abdominal hysterectomy and bilateral salpingo-oophorectomy is the basic treatment for all patients with stage I endometrial carcinoma.
 * <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">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: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">Peritoneal washings are recommended for all patients at time of surgery.
 * <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">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: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">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: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">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: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">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: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">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: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">High-risk patients are sometime treated with a combination of external-beam radiation and vaginal cuff insertion.

<span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">Inoperable Stage I Endometrial Carcinoma


 * <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">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: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">Stage II Endometrial Carcinoma


 * <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">Patients with stage II endometrial carcinoma are subdivided into those with endocervical glandular involvement and those with cervical stromal invasion.
 * <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">The gynecologic oncologic community favors surgery followed by post-op radiation, based on histologic findings.
 * <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">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: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">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: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">Stage III Endometrial Carcinoma


 * <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">Treatments for stage III disease must be individualized.
 * <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">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: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">All stage III patients are candidates for post-op radiation after surgical staging and debulking of the tumor.
 * <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">Radiation fields are defined by the histologic extent of the tumor.
 * <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">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: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">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: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">Stage IV Endometrial Carcinoma


 * <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">Medically inoperable patients with bladder or rectal wall involvement without pelvic wall fixation may be considered for pelvic exenteration.
 * <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">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: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">Radioactive Phosphorus

<span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;"> Chemotherapy
 * <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">Intraperitoneal <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 80%; vertical-align: super;">32 P is effective in decreasing recurrences in selected patients with subclinical intraperitoneal disease. The usual dose is 15 mCi.
 * <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">It is strongly recommended not to combine this treatment with external-beam radiation to the pelvis because of excessive bowel toxicity.

<span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;"> Recurrent Endometrial Carcinoma
 * <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">Doxorubicin (Adriamycin) is the principal theraputic agent used to treat patients with metastatic endometrial cancer.

<span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;"> Radiation Therapy Techniques <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">
 * <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">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: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">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: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">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: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">Vaginal recurrences can receive boost radiation with intracavitary or interstitial radiation therapy to bring the total tumor dose to 80 Gy.
 * <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">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: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">Radiation therapy in indicated for palliation.
 * <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">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: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">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: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">Treatment can be delivered using a 4-field box technique to provide a homogeneous dose distribution.
 * <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">If external-beam therapy alone is to be used post-op, a dose of 45-50 Gy is indicated.
 * <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">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: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">For pre-op intracavitary insertions, the vaginal wall should be irradiated.
 * <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">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: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">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: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">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. 1

4-field Box Technique

<span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">AP/PA and Lateral Treatment Field DRR's





<span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">RF Treatment Plan w/ Midline Block



<span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">RF AP/PA and Lateral DRR's w/ Midline Block





<span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">HDR Brachytherapy Treatment Plan



<span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;"> HDR Brachytherapy Source Verification DRR's AP and L Lateral





<span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">All treatment plan snapshots and field photos provided by Central Mississippi Medical Center in Jackson, MS. ||
 * TD5/5: || [[image:bladder_td5.5.jpg]]

<span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">Table provided by Wikibooks. <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 88%; vertical-align: super;">6 || References: <span style="color: #ff00ff; font-family: 'Times New Roman',Times,serif;">1. Chao KS, Perez CA, Brady LW. Radiation Oncology Management Decisions. 2nd edition. Philadelphia, PA: Lippincott Williams & Wilkins. 2002. 511-514, 511-512, 514-518 . 2. <span style="color: #ff00ff; font-family: 'Times New Roman',Times,serif; font-size: 10pt;">Gunderson, LL & Tepper, JE. (Eds.) //<span style="font-family: 'Calibri','sans-serif';">Clinical Radiation Oncology //. 2nd edition. Philadelphia, PA: Elsevier, Churchill & Livingstone. 2007: 1360-1363. <span style="color: #0000ff; font-family: 'Times New Roman',Times,serif; font-size: 10pt;">3. Rubin ,<span style="color: #0000ff; font-family: 'Times New Roman',Times,serif;"> P. //Clinical Oncology A Multidisciplinary Approach for Physicians and Students// //. <span style="color: #0000ff; font-family: 'Times New Roman',Times,serif;">8th Edition. Philadelphia, Pennsylvania: W.B. Saunders Company. 2001; 480-481. // <span style="color: #0000ff; font-family: 'Times New Roman',Times,serif;">4. Washington CM, Leaver D. //Principles and Practice of Radiation Therapy//. Second Edition. St. Louis, Missouri: Mosby, Inc : 2004; 781-782. <span style="color: #008000; font-family: 'Times New Roman',Times,serif; font-size: 110%;">5. Perez CA, Brady LW, Halperin EC, Schmidt-Ullrich RK. //Principles and Practice of Radiation Oncology.// 4th edition. Philadelphia, PA: Lippincott Williams & Wilkins. 2004: 1919-1920. <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 121%;">6. Radiation Oncology/Toxicity/Emami. Wikibooks. Available at: <span style="font-family: 'Times New Roman',Times,serif; font-size: 110%;">[]. <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 121%;">Accessed: January 5, 2010. <span style="color: #008080; font-family: 'Times New Roman',Times,serif; font-size: 110%;">7. Lenhard RE, Osteen RT, Gansler T. The American Cancer Society's Clinical Oncology. 1st ed. Atlanta, GA: ACS, Inc. 2001: 423.

<span style="color: #ff00ff; font-family: 'Times New Roman',Times,serif;">