Ovarian

The American Cancer Society estimated that there would be 21,880 new cases of ovarian cancer in 2010 and 13,850 deaths from the disease.[1] The 2010 estimates are 21,880 cases and 13,850 deaths.[1] Epithelial ovarian cancer is the eighth most common cancer in women, and uterine (corpus and endometrial) is fourth.[1] The ovaries are the ninth most common site of cancer in women, accounting for approximately 3% of all new cases, but ovarian cancer causes 5% of cancer deaths—more than any other cancer of the female reproductive system. However, during 2001–2005, the incidence of ovarian cancer declined at a rate of 2.4% annually, and the death rate from ovarian cancer has been stable since 1998.[1] Ovarian cancer is more common among American women in the white population than it is among those in the black population.[1] Epithelial ovarian cancer can occur in females as young as 15 years, but the mean age is 56 years.[1] In the United States, incidence of ovarian carcinoma is approximately 15 cases per 100,000 women per year for women aged 50-54 years, rising to 35 cases per 100,000 women for women aged 70-74 years. Ovarian cancer is the 4th leading cause of cancer related deaths in women.[1] || It is the most common in women aged 50-70 years.[1] The environmental and physiologic risk factors include: Nulliparity Infertility Use of fertility drugs Consumption of fat, milk products, and coffee Perineal use of talc The Genetics risk is: the identification of the BRCA1 (breast cancer 1) and the HNPCC (hereditary nonpolyposis colorectal/ovarian cancer) genes should make it possible to accurately predict ovarian cancer susceptibility in women from high-risk families[1] Non-risk factors: Multiple pregnancies, long-term use of oral contraceptives, extended duration of breast-feeding, tubal ligation or hysterectomy, age at menarche, first birth delivery, menopause, and the use of hormone replacement therapy.[1] || || []. Some histotypes of ovarian cancer are: [6] GX - Grade cannot be evaluated. G1 - Cell appearance is closely related to normal tissue (well differentiated). G2 – Cells appear somewhat abnormal (moderately diffentiated). G3 – Cell appearance is abnormal, almost unrecognizable (poorly differentiated). || T0 || __** FIGO **__ || __** Definition **__ Primary tumor cannot be assessed || N1 || IIIC || Peritoneal metastasis beyond the pelvis, <2 cm in greatest dimension and /or regional lymph node metastasis || [2] ||  || Usually, these will subside within 2-4 weeks after the completion of treatment. 10-15% of patients may experience persistent bloating or diarrhea. [3] Another acute side effect of treating abdominal fields is upper gastrointestinal bleeding. [7] Late effects may include:
 * **Epidemiolgy:** || In the United States, the incidence of ovarian cancer is 33 cases per 100,000 women age of 50 years or older.[1] The average patient age at diagnosis is 57 years.[1] The estimated lifetime risk is 1 case in 70 women, which is a 1.4% lifetime incidence.[1]
 * **Etiology:** || The precise cause of ovarian cancer is unknown, but several risk and contributing factors have been identified.[1] Hippisley-Cox and Coupland developed an algorithm to determine risk of breast cancer in women with and without symptoms.[1] In their cohort study, 10% of women with the highest-predicted risk had 63% of all ovarian cancers diagnosed over the next 2 years.
 * **Signs & Symptoms:** || * 11-15% of ovarian cancers present with pelvic pain, a pelvic mass, and serosanguinous vaginal discharge. These three symptoms together are known as Latzko’s triad.
 * A rare symptom of ovarian cancer is lower abdominal pain which is somewhat relieved with intermittent watery, yellowish discharge known as Hydrops tubae profuens.
 * 15- 25% of ovarian cases present with nonspecific gastrointestinal symptoms.
 * 5% of adnexal masses (mass found in the adnexal area of the uterus) are found to be malignant most commonly in postmenopausal women. Surgical exploration is then indicated.
 * Unfortunately, most ovarian diagnosis are made after pelvic and abdominal spread presenting with pain. [2]
 * ACS recommends yearly pelvic screenings starting at age 18 or earlier if sexually active as a first line of defense for early detection.[3] This is especially important in women with family history of BRCA1 or BRCA2 suppressor genes, which can increase risk.[2] ||
 * **Diagnostic Procedures:** || # Patients suspected to have ovarian cancer should have a full diagnostic workup and preoperative evaluation which should include:
 * History: full patient and family
 * Physical assessment including bimanual pelvic examination.[2] This type of palpation exam is responsible for finding many large or late stage ovarian masses and very few early stage but is the least invasive procedure for detection.[3]
 * 1) Color flow Doppler with transvaginal ultrasound is best suited study used for adnexal tumors.[2]
 * 1) Upper abdominal extension is found with using CT.[2]
 * 2) Blood cell count, blood urea nitrogen, criatinine, liver enzymes and CA 125 levels should all have laboratory evaluation. Patients with some types of ovarian tumors, should have levels of CA 19-9 monitored. The most useful markers for germ cell tumors are Human chronic gonadotropin and alpha-fetoprotein. [2]
 * 3) A preoperative surgical clearance should also be performed. [2]
 * **Histology:** || [[image:uwlmedicaldosimetry2012/OCpic.jpg caption="Histotypes of ovarian cancer"]]
 * Glandular and epithelial/ surface epithelial- stromal tumor **
 * CMS
 * Ovarian serous cystadenoma
 * Mucinous cystadenoma
 * Cystadenocarcinoma (Papillary serous cystadenocarcinoma)
 * Krukenberg tumor
 * Endometrioid tumor
 * Clear-cell ovarian carcinoma
 * Brenner tumor
 * Sex cord-gonadal stromal **
 * Leydig cell tumor
 * Sertoli cell tumor
 * Sertoli-Leydig cell tumor
 * Thecoma
 * Granulosa cell tumor
 * Luteoma
 * Sex cord tumor with annular tubules
 * Germ cell **
 * Dysgerminoma
 * Nongerminomatous
 * Embryonal carcinoma
 * Endodermal sinus tumor
 * Gonadoblastoma
 * Teratoma/Struma ovarii
 * Choriocarcinoma
 * Fibroma **
 * Meigs syndrome ||  ||   ||   ||
 * **Lymph node drainage:** || The main lymphatic drainage from the ovary is to the periaortic nodes at the level of the renal veins. The inguinal and external iliac nodes may also be involved by a reversing of lymphatic flow. [2] ||
 * **Metastatic spread:** || Distribution occurs by transcoelomic, lymphatic, or hematogenous spread. All peritoneal areas are at risk for tumor spread and growth. Peritoneal surfaces of the diaphragm, liver, and spleen are commonly effected. Hematogeneous metastasis happens in the liver, lung, and pleura. Less common sites of metastatic spread are to the bone, kidney, bladder, skin, adrenal gland, and spleen. [2] ||
 * **Grading:** || Grade describes how closely cancer cells resemble normal tissue through microscopic examination. Tumor grading is based on the degree of differentiation of the malignant cells, nuclear features, and an estimate of growth rate as indicated by the mitotic rate. [3]
 * **Staging:** || Staging of ovarian carcinoma should be done during surgical exploration. Staging classification done by the International Federation of Gynecology and Obstetrics (FIGO) is the most commonly used system [2]: ||  ||   ||   ||
 * __** TNM **__
 * TX ||  || No evidence of primary tumor ||
 * T1 || I || Tumor limited to one ovary(one or both) ||
 * T1a || IA || Tumor limited to one ovary; capsule intact; no malignant cells in ascites or peritoneal washings ||
 * T1b || IB || Tumor limited to both ovaries; capsules intact, no tumor on ovarian surface; no malignant cells in ascites or peritoneal washings ||
 * T1c || IC || Tumor limited to one or both ovaries with any of the following: capsule ruptured, tumor on ovarian surface, malignant cells in ascites or peritoneal washings ||
 * T2 || II || Tumor involves one or both ovaries with pelvic extension ||
 * T2a || IIA || Extension and/or implants on the uterus and/or tube(s); no malignant cells in ascites or peritoneal washings ||
 * T2b || IIB || Extension to other pelvis tissues; no malignant cells in ascites or peritoneal washings ||
 * T3&/or N1 || III || Tumor involves one or both ovaries with microscopically confirmed peritoneal metastasis outside the pelvis and/or regional lymph nodes ||
 * T3a || IIIA || Microscopic peritoneal metastasis beyond the pelvis ||
 * T3b || IIIB || Macroscopic peritoneal metastasis beyond the pelvis, ≤2 cm in greatest dimension ||
 * T3c&/or
 * M1 || IV || Distant metastasis (excludes peritoneal metastasis) ||
 * NX ||  || Regional lymph nodes cannot be assessed ||
 * N0 ||  || No regional lymph node metastasis ||
 * N1 ||  || Regional lymph node metastasis ||
 * MX ||  || Distant metastasis cannot be assessed ||
 * M0 ||  || No distant metastasis ||
 * M1 ||  || Distant metastasis (excludes peritoneal metastasis)
 * M0 ||  || No distant metastasis ||
 * M1 ||  || Distant metastasis (excludes peritoneal metastasis)
 * **Radiation side effects:** || Acute effects may include:
 * Fatigue
 * Diarrhea
 * Nausea
 * Dermatitis
 * Dysuria [3]
 * Menopause
 * Vaginal dryness/narrowing/shortening
 * Chronic cystitis
 * Proctosigmoiditis
 * Enteritis
 * Bowel obstruction [7] ||
 * **Prognosis:** || Tumor stage, volume of postoperative residual disease and tumor grade are the major independent prognosticators for epithelial cancers. [7] Nearly all women survive ovarian cancer post diagnosis and have a 46% survival rate after five years of diagnosis but weigh heavily on the initial staging of the tumor, cell type and grade. The survival rate also is heavily correlated based on stage of disease and age of the patient whereas younger women have a better chance at survival than those over the age of 65. As considering if the tumor has moved outside the pelvis, spread to other regions of the pelvis or is still contained with in the ovary or ovaries. [2]

Stage overall survival rates chart: Overall survival 1= 90% 2= 80%  3= 15-20%  4= Less than 5%
 * __ Stage and 5 year survival __**

An important prognosticator for early-stage disease is the Histological grade of tumor tissue with diagnosing at an earlier stage resulting in a higher survival rate. Graded on a scale of 1 to 3, 1 being similar to normal tissue and 3 being vastly different (poorly defined) than normal tissue.

Grade survival rate chart: 1= 97% 2= 78%  3= 62%
 * __ Grade and survival rate __**

Early stage diseases that are predictive of high probability of relapse after complete tumor removal are degree of differentiation, presence of dense adhesions between tumor and pelvic organs and presence of ascites. [2] Another test is to evaluate the ploidy (the amount of DNA in the tumor) of the tumor to measure the malignancy of the tumor. Those that was aneuploid and more aggressive verse diploid had a shorter life should have an impact on survival rates. [2] ||
 * **Treatments:** || The treatment of ovarian cancer can be done in several methods and often with a combination of two or three. Most often surgery is the first method followed by postoperative chemo then pending on initial stage and grade hormone therapy and radiation may be used to treat.

Surgery; Other than surgical staging, Cytoreductive surgery or referred to as tumor debulking is one of the most important components in surgical management for patients with ovarian cancer to remove a large portion of the tumor. There are three different types of tumor debulking.[2]
 * Primary cytoreductive surgery: performed before adjuvant therapy
 * Interventional cytoreductive surgery: performed after a few cycles of chemotherapy when optimal debulking was not possible.
 * Secondary cytoreductive surgery: performed after the completion of chemotherapy

Once a patient has completed a planned course of treatment after initial surgical staging, cytoreductive surgery, and chemotherapy (platinum-based chemo drug), a second look laparotomy (surgical evaluation of the entire peritoneal cavity and retroperitoneal to evaluate nodes and multiple biopsy are taken) may be performed to evaluate the amount of residual tumor after debulking surgery. If second look laparotomy is positive, treatment options may include external beam radiation, intraperitoneal radioactive organic phosphate, monoclonal antibodies, and chemotherapy. [7]

Radiation therapy; Whole abdominal pelvic irradiation may be used but is somewhat controversial due to the advancement of newer chemo drugs and staging protocols. If external beam is chosen the field should include the entire peritoneal cavity to reduce the chance of disease recurrence.

Field arrangement and doses. [2]
 * Open field treating the peritoneal cavity, periaortic, pelvic, and mesenteric lymph nodes, and the entire diaphragm
 * High energy parallel-opposed fields are recommended, but carefully planned 4-field may also be used. Superior border: 2 cm above the domes of the diaphragm
 * Lateral borders: 2 cm beyond the lateral peritoneum
 * Inferior border: bottom of obturator foramen
 * Kidney block: 5 HVL posterior block can be used after receiving a dose of 18 Gy
 * Liver block: 1 HVL anterior block can be used after receiving a dose of 25 Gy
 * Abdominal dose: 22.5-30 Gy (1-1.5 Gy/fx)
 * The pelvic fields can be boosted to a dose of 45-50 Gy (1.8-2.0 Gy/fx

picture to show field design: Phosphorus 32 Chemotherapy;[2] Hormonal Therapy;[2] Organ 1/3 2/3 3/3 Lung 4500cGy 3000cGy 1750cGy Liver 5000cGy 3500cGy 3000cGy Spinal cord 5000cGy (5cm) 5000cGy(10cm) 4700cGy(20cm) Bone marrow 3000cGy Stomach 6000cGy 5500cGy 5000cGy Rectum 6000cGy Bladder 8000cGy 6500cGy Kidney 5000cGy 3000cGy 2300cGy Small bowel 5000cGy 4000cGy || 2. Chao KS, Perez CA, Brady LW. Radiation Oncology: Management Decisions. Philadelphia, PA: Lippincott Williams & Wilkins; 2002. 3. Lenhard RE, Osteen R, Gansler T. The American Cancer Society’s Clinical Oncology. Williston, VT: Blackwell Publishing, Inc; 2001. 4. Ovarian Cancer Screening. 2011. Available at: [] .Accessed on: June 22, 2012. 5. Abdominal mass. 2008. Available at: [] .Accessed on: June 22, 2012. 6. Ovarian cancer. Wikipedia. June 5, 2012. Available at: []. AccessedJune 11, 2012. 7. Washington CM, Leaver D. Principles and Practice of Radiation Therapy. St. Louis, MO: Mosby; 2010. ||
 * Common intraperitoneal radioisotope
 * 15-20 mCi dose, A surface dose of P-32 10mCi is estimated at 30Gy.
 * Administered within first 12 hours following surgery, P-32 is then distributed to the peritoneal surface within the first 24 hours.
 * Six cycles of cisplatin and cyclophosphamide, although paclitaxel is the most promising new drug (long-term data not available). There is no benefit to high dose cisplatin.
 * Chemotherapy has become the standard of care after surgical procdures for ovarian cancer.
 * Intraperitoneal chemotherapy remains investigational with no randomized tirals established to show benefit.
 * After maximum chemotherapy has been used hormonal therapy is an option to treat reoccurrence a response of 10% has been seen in these cases. ||
 * **TD 5/5:** || TD 5/5
 * **References** || 1. Green E.G. Ovarian Cancer. Medscape. May 1, 2012. Available at: [|http://emedicine.medscape.com/article/255771-overview#a0156]. Accessed on: June 20, 2012.

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