Ovarian


 * Epidemiology: || Ovarian carcinomas are the fourth-leading cause of cancer-related death in women in the United States; 25,400 new cases of ovarian cancer were predicted in 1998 with 14,500 deaths. Carcinoma of the ovary is a disease of older women, with a peak incidence in the fifth to seventh decade. It is rarely seen before menarche, but when it is seen, ovarian germ cell tumors predominate. 1 ||
 * Etiology: || Nulliparous women are at an increased risk of ovarian cancer compared with those who have borne children; multiple pregnancies exert an increasingly protective effect. Oral contraceptives have a protective effect, particulary in nulliparous women.

Hereditary site-specific ovarian cancer syndrome, hereditary breast/ovarian cancer syndrome, and Lynch II cancer family syndrome occur as autosomal-dominant traits with a variable penetrance. The last is characterized by nonpolyposis colorectal cancer, endometrial cancer, and ovarian cancer. Peutz-Jeghers syndrome is associated with an increased risk of sex cord-stromal tumors.

Sunlight, which is related to vitamin D synthesis for ovarian cancers, has been reported as a protective factor; low incidences of this type of cancer are found in countries with high amounts of sunlight. Depot medroxyprogesterone acetate and short-term use of tamoxifen have not conclusively been shown to be associated with an increased risk of ovarian cancer. 1 || Less than 10% are primary germ cell, sex cord, or stromal tumors. 1  ||
 * Signs & Symptoms: || Because early gastrointestinal symptoms are nonspecific, women present with early-stage disease only 15% to 25% of the time. Detection of early-stage disease usually occurs by palpation of an asymptomatic adnexal mass on routine examination. Most adnexal masses are not malignant, and in premenopausal women, ovarian cancer represents fewer than 5% of adnexal neoplasms. An adnexal mass in a postmenopausal woman has a higher likelihood of malignancy, and surgical exploration is indicated. Most wormen are diagnosed after disease has spread beyond the pelvis and present as abdominal pain or discomfort with increased abdominal girth related to ascites or large intraabdominal masses. 1 ||
 * Diagnostic Procedures: || * The diagnostic workup and preoperative evaluation of a patient suspected of having ovarian malignancy should include an initial full history and physical assessment, including bimanual pelvic examination.
 * Transvaginal ultrasonography is more sensitive in the assessment of adnexal masses, especially when combined with color flow Doppler.
 * CT is useful in detection of upper abdominal and retroperitoneal disease.
 * Routine laboratory studies should include a complete blood cell count, blood urea nitrogen, creatinine, liver enzymes, and CA 125 level. Other tumor markers have been investigated to enhance the specificity of CA 125.
 * CA 19-9, along with carcinoembryonic antigen, is useful in monitoring patients with mucinous subtypes of ovarian cancer.
 * Human chorionic gonadotropin and a-fetoprotein are the most useful markers for germ cell tumors.
 * Patients also should undergo routine preoperative surgical clearance. 1 ||
 * Histology: || 85-90% are epithelial (serous cystadenocarcinoma is the most common of these, accounting for 42%).
 * Lymph Node Drainage: || Drainage for Ovarian Cancer 5

Lymphatic drainage is primarily to the periaortic nodes at the level of the renal veins. The external iliac and inguinal lymph nodes may be involved by retrograde lymphatic flow. 1 || || •Toxicity after abdominal pelvic irradiation is classified as acute or late. •Acute effects occur during treatment and up to 1 month after completion of therapy. •75% of patients experience mild diarrhea and 67% are nauseous; vomiting occasionally occurs. •Hematologic toxicity is generally mild. •Toxicity from abdominal pelvic irradiation tends to be more severe after chemotherapy than when it is used as a single modality. This is because patients receiving combined-modality treatment usually have advanced disease and are at a high risk for major bowel complications regardless of radiation therapy. •The risk of radiation sequelae increases with increasing stage, increasing size of tumor residuum and abdominal carcinomatosis. 1 ||
 * Metastatic Spread: || The most common node of metastic spread is the periaortic lymph nodes and are involved 10% to 20% of the time in local disease and 80% of the time in advanced diseases. Hematogenic spread is extremely rare in ovarian cancer. Metastases to the brain, lung, and liver have been occasionally reported. The earliest and most common sites of ovarian tumor spread are the pelvic reproductive organs. 10% of patients have tumors in both ovaries. Becacause of the high frequency of synchronous and metachronous involvement of both ovaries, the uterus, fallopian tubes, total abdominal hysterectomy and bilateral salpingo-oophorectomy has been accepted as the routine surgical procedure in ovarian cancer. 1 ||
 * Grading: || **GX:** The tumor grade cannot be evaluated.
 * G1:** The tumor cells are well differentiated.
 * G2:** The tumor cells are moderately differentiated.
 * G3:** The tumor cells are poorly differentiated.
 * G4:** The tumor cells are undifferentiated. 4 ||
 * Staging: || Ovary FIGO Staging System 1
 * Radiation Side Effects: || Sequelae of Treatment
 * Prognosis: || •Tumor stage, volume of postoperative residual disease and tumor grade are the major independent prognosticators for epithelial cancers. Histologic subtypes of malignant epithelial ovarian neoplasms are of limited prognostic significance. Refer to the Tables as follows. 1

 •Histological grade is a particularly important prognosticator for early-stage disease.



•Tumor variables of stage I disease 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.

•Figure 47-1 as follows shows the classification of patients into 3 distinct risk groups based on stage, postoperative residual tumor volume and grade. The low-risk group requires no adjuvant therapy and has excellent survival with surgery being the only treatment modality. The intermediate-risk group constitutes almost 35% of patients with ovarian cancer; abdominopelvic irradiation is the most appropriate treatment. This group primarily includes patients with stage I and II disease but patients with stage III disease, grade 1 optimallly debulked (less than 2cm residuum) with residual disease located in the pelvis are amenable to abdominopelvic irradiation. 1



•Other studies have found tumor ploidy to be a significant prognosticator. Aneuploid tumors are more aggressive than diploid tumors and are generalyy of higher stage at presentation; they also have a shorter median survival time. 1 || -Cytoreductive surgery (tumor debulking) is one of the most important components in surgical management for patients with ovarian cancer. There are three types: -Primary cytoreductive surgery: performed before adjuvant therapy -Interventional cytoreductive surgery: performed after a few cycles of chemotherapy -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, a second look laparotomy (a complete surgical evaluation of the entire peritoneal cavity and retroperitoneum) may be performed. -If second look laparotomy is positive, treatment options may include external beam radiation, intraperitoneal radioactive organic phosphate, monoclonal antibodies, and chemotherapy. <span style="color: #00ff00; font-family: Arial,Helvetica,sans-serif; font-size: 80%; vertical-align: super;">1 <span style="color: #00ff00; font-family: Arial,Helvetica,sans-serif;">
 * Treatments: || <span style="color: #00ff00; font-family: Arial,Helvetica,sans-serif;">Surgery:

Radiation Therapy: -Whole abdominal pelvic irradiation may be curative (all areas of postoperative disease recurrence, thus the entire peritoneal cavity should be included). -Open field treating the peritoneal cavity, periaortic, pelvic, and mesenteric lymph nodes, and the entire diaphragm. -High energy parallel-opposed fields is recommended, but carefully planned 4-field may also be used. -Superior border: 2 cm above the domes of the diaphragm -Inferior border: bottom of obturator foramen -Lateral borders: 2 cm beyond the lateral peritoneum -Pelvic boost fields are usually AP/PA or 4-field technique. -Abdominal dose: 22.5-30 Gy (1-1.5 Gy/fx) -Pelvic fields can be boosted to a dose of 45-50 Gy (1.8-2.0 Gy/fx). -Liver block: 1 HVL anterior block can be used after receiving a dose of 25 Gy -Kidney block: 5 HVL posterior block can be used after receiving a dose of 18 Gy

-Patients with minimal or no residual disease after surgery may be treated with the most common intraperitoneal radioisotope, phosphorus 32. -15-20 mCi is usually used. -Administered within first 12 hours following surgery. -2 peritoneal catheters are placed during laparoscopy or may be placed percutaneously using a specialized central venous catheter placed under local anesthesia. -Phosphorus 32 becomes distributed to the peritoneal surface within the first 24 hours. -The estimated tissue surface dose form 10 mCi is about 30 Gy. <span style="color: #00ff00; font-family: Arial,Helvetica,sans-serif; font-size: 80%; vertical-align: super;">1 <span style="color: #00ff00; font-family: Arial,Helvetica,sans-serif;">

Chemotherapy: -The standard of care has been to receive systemic chemotherapy post-operatively. -Six cycles of cisplatin and cyclophosphamide, although paclitaxel is the most promising new drug (long-term data not available). -Intraperitoneal chemotherapy remains investigational. <span style="color: #00ff00; font-family: Arial,Helvetica,sans-serif; font-size: 80%; vertical-align: super;">1 <span style="color: #00ff00; font-family: Arial,Helvetica,sans-serif;">

Hormone Therapy: -An option for patients with recurrences after maximal chemotherapy has been used. -The overall response rate is 10%. <span style="color: #00ff00; font-family: Arial,Helvetica,sans-serif; font-size: 80%; vertical-align: super;">1 <span style="color: #00ff00; font-family: Arial,Helvetica,sans-serif;">

//Management of Dysgerminoma (most common germ cell tumor~approx. 3% of all ovarian malignancies)// // -Stage IA: requires unilateral salpingo-oophorectomy and inspection of peritoneal cavity. Biopsy should be performed on suspicious areas and retroperitoneal nodes. Radiation to periaortic and ipsilateral hemipelvic lymph noes following surgery. -Radiation set-up: Upper border: T10-T11 Lower border: Top of obturator foramen Lateral border: 2 cm beyond pelvic inlet on ipsilateral side and wide enough to include the periaortic nodes on the contralateral side (left renal hilum should also be included) Total dose of 25-30 Gy (7.5-9 Gy per week) should be used -Beyond Stage IA: Total abdominal hysterectomy and bilateral salpingo-oophorectomy. -Recurrences are usually treated with chemotherapy, but can also be treated with radiation therapy. // <span style="color: #00ff00; font-family: Arial,Helvetica,sans-serif; font-size: 80%; font-style: normal; vertical-align: super;">1 || <span style="color: #0000ff; font-family: Arial,Helvetica,sans-serif;">* <span style="color: #0000ff; font-family: Arial,Helvetica,sans-serif; font-size: 80%; vertical-align: super;">3 ||
 * TD5/5: || <span style="color: #0000ff; font-family: Arial,Helvetica,sans-serif;">TD 5/5 Table for OAR in the abdominal-pelvic portal. <span style="color: #0000ff; font-family: Arial,Helvetica,sans-serif; font-size: 80%; vertical-align: super;">2
 * Planning Photos: || <span style="color: #0000ff; font-family: Arial,Helvetica,sans-serif;"><span style="color: #0000ff; font-family: Arial,Helvetica,sans-serif;">Treatment portal for abdominal-pelvic radiation therapy. Parallel opposed anterior and posterior fields are used to encompass the entire peritoneum. <span style="color: #0000ff; font-family: Arial,Helvetica,sans-serif; font-size: 80%; vertical-align: super;"> <span style="color: #0000ff; font-family: Arial,Helvetica,sans-serif; font-size: 80%; vertical-align: super;">1<span style="color: #0000ff; font-family: Arial,Helvetica,sans-serif; font-size: 80%; vertical-align: super;">

|| <span style="font-family: Arial,Helvetica,sans-serif;">**References** 1. Chao KS, Perez CA, Brady LW. //<span style="font-family: Arial,Helvetica,sans-serif;">Radiation Oncology - Management Decisions. // <span style="font-family: Arial,Helvetica,sans-serif;"> 2nd ed. Philadelphia: Lippincott, Williams & Wilkins, 2002: 519-530. 2. Emami B, Lyman J, Brown A, et al. Tolerance of normal tissue to therapeutic irradiation. Int J Radiat Oncol Biol Phys. 1991; 21: 109-122. 3. Rembert J, Hsu I. Ovarian Cancer. In: Hansen EK, Roach M. //<span style="font-family: Arial,Helvetica,sans-serif;">Handbook of Evidence-based Radiation Oncology, //<span style="font-family: Arial,Helvetica,sans-serif;"> 1st ed. New York: Springer, 2007: 358-367. 4. Washington CM, Leaver D, eds. //<span style="font-family: Arial,Helvetica,sans-serif;">Principles and Practice of Radiation Therapy, 2 // <span style="font-family: Arial,Helvetica,sans-serif;">nd ed: Philadelphia: Mosby Inc, 2004: 780-707. 5. Lenards, N. //<span style="font-family: Arial,Helvetica,sans-serif;">Clinical Oncology for Medical Dosimetrists: Ovary. // <span style="font-family: Arial,Helvetica,sans-serif;"> Course content - Ovary, Slide 7.

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